International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 6 Issue 1 April June 2013

MS ID: IJPSN-5-11-12-BOLMOL

Review Article

Recent Advances in Nanosponges as Drug Delivery System

1*

Uday B. Bolmal , F.V.Manvi , Kotha Rajkumar , Sai Sowjanya Palla , Anusha Paladugu and Korivi
2
Ramamohan Reddy
1
Department of Pharmaceutics, and 2Department of Pharmacology, KLEUs College of Pharmacy, JNMC Campus,
Belgaum, Karnataka, India.

Received November 5, 2012; accepted February 20, 2013

ABSTRACT
Major problem of many newly developed chemical entities is their
poor solubility in water and pharmacokinetic issues. These poorlywater soluble drugs show many problems in formulating them in
conventional dosage forms and the critical problem associated is
its very low bio-availability. Nanotechnology has attracted
increasing attention during recent years and it can resolve the
problems associated with solubility and bio-availability.
Nanosponges are a part of nanotechnology. Nanosponges
delivery system, which was originally developed for topical
delivery of drugs, can also be used for controlled oral delivery of
drugs using water soluble and bioerodible polymers.

Nanosponges are tiny sponges with a size of about a virus, which

can be filled with wide variety of drugs. These tiny sponges can
circulate around the body until they encounter the specific target
site and stick on the surface and begin to release the drug in a
controlled and predictable manner. Because the drug can be
released at the specific target site instead of circulating throughout
the body it will be more effective for specific disease targeted
treatment. Another important character of these sponges is their
aqueous solubility; this allows the use of these systems effectively
for drugs with poor solubility.

Key Words: Nanosponges; Topical drug delivery; Controlled release; Poor solubility; Biodegradable polymers.

Introduction
An
ideal
drug
therapy
achieves
effective
concentration of drug at the target site for a specified
period of time in order to minimize general and local side
effects. To obtain a desirable therapeutic response, the
correct amount of drug should be transported and
delivered to the site of action with subsequent control of
drug input rate. The distribution of drug to other tissues
therefore seems unnecessary, wasteful and a potential
cause of toxicity. Targeted drug delivery is the delivery of
drug to receptor, organ or any part of the body to which
one wishes to deliver the drug exclusively.
Effective targeted drug delivery systems have been a
dream for a long time now but it has been largely
frustrated by the complex chemistry that is involved how to get them to the right place in the body and how to
control the release of the drug to prevent overdoses. The
developments of new and complex molecules called
nanosponges have the potential to solve these problems.
Nanosponges are a new class of tiny sponges that are
about the size of a virus, filling them with a drug and
attaching -special chemical "linkers" that bond
preferentially to a feature found only on the surface of
tumour cells and then injecting them into the body.
These tiny sponges circulate around the body until they
encounter the surface of a tumour cell where they stick
on the surface (or are sucked into the cell) and begin
releasing their potent drug in a controllable and
predictable fashion.

Nanosponges (NS) are like a three-dimensional

network or scaffold, whose backbone is a long length of
polyester. It is mixed in solution with small molecules
called cross-linkers that act like tiny grappling hooks to
fasten different parts of the polymer together. The net
effect is to form spherically shaped particles filled with
cavities where drug molecules can be stored. The
polyester is biodegradable, so it breaks down gradually in
the body (David, 2011).
It is also possible to control the size of nanosponge
particles. By varying the proportion of cross-linker to
polymer, the nanosponge particles can be made larger or
smaller. This is important because research has shown
that drug delivery systems work best when they are
smaller than 100nm, about the depth of the pits on the
surface of a compact disc. The nanosponge particles used
in the current study were 50 nm in size (David, 2011).
The simple chemistry of polymers and cross linkers
does not pose many problems in the preparation and this
technology can be easily ramp up to commercial
production levels. Nanosponges are water soluble but
does not breakup chemically in water. They mix with
water and use as a transport fluid. They can be used to
mask unpleasant flavours, to convert liquid substances to
solids. The chemical linkers enable the nanosponges to
bind preferentially to the target site.
Nanosponges are a new class materials made of
microscopic particles with few nanometres in range
where a large variety of substances can be encapsulated.
1934

1935

Bolmal et al: Recent Advances in Nanosponges as Drug Delivery System

These particles are capable of carrying both lipophilic

and hydrophilic substances and of improving the
solubility of poorly water soluble molecules (Trotta et al.,
2007). Nanosponges can be administered by different
routes besides oral route which protect the degradable
molecules like proteins and enzymes. Nanosponges are
tiny mesh-like structures with nanoparticle sized system
to deliver the drug payload, that may revolutionise the
treatment of many diseases and early trials suggest this
technology is up to five times more effective at delivering
drugs for breast cancer than conventional methods
(David F, 2011).
Predictable release is one of the major advantages of
this system compared to other nanoparticle delivery
systems under development. When they reach their
target, many other nanoparticle delivery systems unload
most of their drug in a rapid and uncontrollable fashion.
This is called the burst effect and makes it difficult to
determine effective dosage levels, whereas nanosponges
when they reach their target site the drug is released in
a predictable and controlled manner which helps to
determine the effective dosage levels.
The nanosponges are encapsulating type of
nanoparticles which encapsulates the drug molecules
within its core. By the method of associating with drugs,
the nanoparticles can be classified into:
1. Encapsulating
nanoparticles:
These
are
represented by nanosponges and nanocapsules.
Nanosponges such as alginate nanosponge, which
are spongelike nanoparticles containing many
holes that carry the drug molecules. Nanocapsules
such as poly(isobutyl-cyanoacrylate) (IBCA) are
also encapsulating nanoparticles. They can entrap
drug molecules in their aqueous core
2. Complexing nanoparticles: These nanoparticles
attract the molecule by electrostatic charges.
3. Conjugating nanoparticles. These nanoparticles
linked to drug molecules through a strong
covalent bond (Trotta et al., 2009).
Nanosponges represent a novel class of nanoparticles
usually obtained by natural derivatives. As compared to
the other nanoparticles, they are soluble both in water
and organic solvents, porous, non-toxic and stable at high
temperatures up to 300C. Due to its 3D structure
containing cavities of nanomeric size, tunable polarity
and high solubility they are able to capture, transport
and selectively release a wide variety of substances.
Furthermore, nanosponges show a remarkable
advantage in comparison with the common nanoparticles:
indeed, they can be easily regenerated by different
treatments, such as washing with eco-compatible
solvents, stripping with moderately inert hot gases, mild
heating, or changing pH or ionic strength. For all these
characteristics, nanosponges have been already employed
in different applied fields, such as cosmetic and
pharmaceutical sectors (Liang L et al., 2002)
The main disadvantage of these nanosponges is their
ability to include only small molecules. The nanosponges
could be either paracrystalline or in crystalline form. The

loading capacity of nanosponges depends mainly on

degree of crystallisation. Paracrystalline nanosponges
can show different loading capacities.
These nanosponges can be magnetized when they are
prepared in the presence of compounds having magnetic
properties (Jenny A et al., 2011). The tiny shape of
nanosponges enables the pulmonary and venous delivery
of nanosponges (Trotta et al., 2007).
The list of polymers and cross linking agents used for
the synthesis of nanosponges are presented in Table-1
(Selvamuthukumar et al., 2012).
TABLE 1
Chemicals used for the synthesis of nanosponges.
Polymers

Crosslinkers

Hyper
cross
linked
Polystyrenes,
Cyclodextrins and its derivatives like Methyl
Cyclodextrin,
AlkyloxycarbonylCyclodextrins, 2-Hydroxy Propyl -Cyclodextrins
and
Copolymers
like
Poly
(valerolactone
-allylvalerolactone),
Poly
(valerolactone-allylvalerolactoneoxepanedione), Ethyl Cellulose and PVA
Diphenyl Carbonate, Diarylcarbonates, DiIsocyanates,
Pyromellitic
anhydride,
Carbonyl-di-Imidazoles,
Epichloridrine,
Glutarldehyde,
Carboxylic
acid
dianhydrides, 2,2-bis(acrylamido) Acetic acid
and Dichloromethane

Advantages of Nanosponges drug delivery system

This technology offers entrapment of wide variety
of ingredients and reduced side effects (Patel et al.,
2012).
Improved stability, increased elegance, and
enhanced formulation flexibility.
Nanosponges systems are non-irritating, nonmutagenic, non-allergenic, and non-toxic (Patel et
al., 2012).
Controlled release - continuous action for more than
12 hours.
Reduces dosing interval and increases the patient
compliance.
Allows incorporation of immiscible liquids which
improves material processing - liquid can be
converted to powders (Khopade et al 1996; Patel et
al., 2008)
These formulations are stable over wide range of pH
(1-11) and temperature (up to 130oC).
These are self-sterilizing as their average pore size
is 0.25m where bacteria cannot penetrate.
These are free flowing, highly compatible with wide
variety of ingredients and cost effective.

Preparation of Nanosponges
1. Emulsion solvent diffusion method
Nanosponges can be prepared by using different
proportions of ethyl cellulose and polyvinyl alcohol.
The dispersed phase containing ethyl cellulose and
drug was dissolved in 20ml dichloromethane and
slowly added to a definite amount of polyvinyl

1936

alcohol in 150ml of aqueous continuous phase. The

reaction mixture was stirred at 1000 rpm for 2 hrs.
The nanosponges formed were collected by filtration
and dried in oven at 400 c for 24 hrs. The dried
nanosponges were stored in vacuum desiccators to
ensure the removal of residual solvent (Sharma et
al., 2011).
2. Nanosponges prepared from hypercross-linkedcyclodextrins
Nanosponges can be obtained by cross linking with
different types of cyclodextrins (CDs) with a
carbonyl or a dicarboxylate compound as a cross
linker (Trotta et al., 2009). The ratio of CDs can be
varied during preparation to improve the drug
loading and to obtain a tailored release
profile(Cavalli et al., 2006, Swaminathan et al.,
2007; Vavia et al., 2006)
-Cyclodextrin nanosponges were prepared as
reported
in
the
patent
by
Trotta
and
Tumiatti(Trottaet al., 2003). 100 ml of Dimethyl
Formamaide (DMF) was placed in a round bottomed
flask and 17.42g of anhydrous -CD was added to
achieve complete dissolution. Then 9.96 g of
carbonyl di-imidazole (61.42mmol) was added and
the solution allowed reacting for 4 hrs at 100oc.
Once condensation polymerization was completed,
the transparent block of hyper cross linked
cyclodextrin was roughly ground and an excess of
de-ionised water added to remove DMF. Finally
residual by-products or unreacted reagents were
completely removed by Soxhlet extraction with
ethanol.
The white powder thus obtained was dried
overnight in an oven at 60o c and subsequently
ground in a mortar. The fine powder obtained was
dispersed in water. The colloidal part that remained
suspended in water was recovered and lyophilised.
The obtained nanosponges are sub-micron in
dimension and with a spherical shape.
3. Solvent method
Mix the polymer with a suitable solvent, in
particular in a polar aprotic solvent such as
dimethylformamide
(DMF),
dimethylsulfoxide
(DMSO). Then add this mixture to excess quantity
of
the
cross-linker,
preferably
in
cross
linker/polymer molar ratio of 4 to 16. Carry out the
reaction at temperature ranging from 10C to the
reflux temperature of the solvent, for time ranging
from 1 to 48hrs. Preferred cross linkers are carbonyl
compounds (dimethyl carbonate and carbonyl
diimidazole) (Jenny A et al., 2011).
After completion of the reaction, allow the
solution to cool at room temperature, then add the
product to large excess of distilled water and
recover the product by filtration under vacuum and
subsequently purify by prolonged Soxhlet extraction
with ethanol. Dry the product under vacuum and
grind in a mechanical mill to obtain homogeneous
powder (Lala et al., 2011).

Int J Pharm Sci Nanotech

Vol 6;Issue 1April June 2013

4. Ultrasound-Assisted synthesis
Nanosponges can be obtained by reacting polymers
with cross-linkers in the absence of solvent and
under sonication. The obtained nanosponges will be
spherical, uniform in size and smaller than 5
microns (Trotta et al., 2007).
In this method di-phenyl carbonate (or)pyromellitic
anhydride is used as cross-linker. An amount of
anhydrous CD was put to react in melted di-phenyl
carbonate at 90oc for at least 5 hrs. Then, the solid
was ground in a mortar and soxhlet extracted with
ethanol to remove either impurities (or) unreacted
diphenyl carbonate. After purification nanosponges
were stored at 25oc until further use (Trotta et al.,
2007; Lala et al., 2011).

Loading of Drug into Nanosponge

Nanosponges for drug delivery should be pre-treated
to obtain a mean particle size below 500nm. Suspend the
nanosponges in water and sonicate to avoid the presence
of aggregates and then centrifuge the suspension to
obtain the colloidal fraction. Separate the supernatant
and dry the sample by freeze drying (Lala et al., 2011).
Prepare the aqueous suspension of Nanosponge and
disperse the excess amount of the drug and maintain the
suspension under constant stirring for specific time
required for complexation. After complexation, separate
the uncomplexed (undissolved) drug from complexed
drug by centrifugation. Then obtain the solid crystals of
nanosponges by solvent evaporation or by freeze drying
(Lala et al., 2011; Jenny et al., 2011).
Crystal structure of nanosponges plays a very
important role in complexation with drug. A study
revealed that paracrystalline nanosponges showed
different loading capacities when compared to crystalline
nanosponges. The drug loading is greater in crystalline
nanosponges than paracrystalline one. In poorly
crystalline nanosponges, the drug loading occurs as a
mechanical mixture rather than inclusion complex
(Shankar et al., 2010)
FACTORS INFLUENCING NANOSPONGES
FORMULATION

Type of polymer
Type of polymer used can influence the formation as
well as the performance of Nanosponges. For
complexation, the cavity size of nanosponges should be
suitable to accommodate a drug molecule of particular
size (Amber et al., 2008).

Type of drug
Drug molecules to be complexed with nanosponges
should have certain characteristics mentioned below
(Amber et al., 2008).
Molecular weight of drug should be in between 100
to 400 Daltons.

1937

Bolmal et al: Recent Advances in Nanosponges as Drug Delivery System

The structure of the drug molecule should contain

no more than five condensed rings
Solubility in water should be less than 10mg/ml
Melting point of the substance should be less than
250C

Temperature
Temperature changes can affect drug / nanosponges
complexation. In general, increase in the temperature
decreases the magnitude of the apparent stability
constant of the drug/nanosponges complex which may be
due to a result of possible reduction of drug/nanosponges
interaction forces, such as van-der Waal forces and
hydrophobic forces with rise of temperature (Rajeswari et
al., 2005).

Method of preparation
Method of preparation.The method of loading the

drug into the nanosponges can affect drug/nanosponge

complexation. However, the effectiveness of a method
depends on the nature of the drug and polymer, in many
cases freeze drying was found to be most effective method
for drug complexation (Rajeswari et al., 2005).
Degree of substitution. The complexation ability of
the nanosponges may be greatly affected by type, number
and position of the substituent on the parent molecule
(Rajeswari et al., 2005).
Characterization of Nanosponges
Inclusion complexes formed between the drug and
nanosponges can be characterized by following methods:
Solubility studies.The most widely used approach to
study inclusion complexation is the phase solubility
method described by Higuchi and Connors, which
examines the effect of a nanosponge, on the solubility of
drug. Phase solubility diagrams indicate the degree of
complexation (Rajeswari et al., 2005; Jenny et al.,
2011). In the solubility studies (Aithal et al., 1995; Wang
et al., 2007) changes in solubility of the guest are plotted
as a function of the cyclodextrin concentration, if the
solubility of a potential guest increases with increasing
cyclodextrin concentration; complex formation in solution
is indicated Solubility studies were performed to
evaluate the drug pH solubilization profile and to assess
the effect of multicomponent complexation on drug
solubility (Fouda et al., 2006; Ribeiro et al., 2007;
Ramnik et al., 2010).

Particle size and polydispersity

The particle size can be determined by dynamic light
scattering using 90 Plus particle sizer equipped with
MAS OPTION particle sizing software. From this the
mean diameter and polydispersity index can be
determined (Shankar et al.,2010).
The polydispersity index (PDI) can also be measured
from Dynamic light scattering Instruments. PDI is an
index of width or spread or variation within the particle
size distribution. Monodisperse samples have a lower
PDI value, whereas higher value of PDI indicates a wider

particle size distribution and the polydisperse nature of

the sample. PDI can be calculated by the following
equation:
PDI = d/davg
Where, d is the width of distribution denoted as SD
and davg is the average particle size denoted as MV (nm)
in particle size data sheet.Table 2 (Wolfgang et al., 2007)
TABLE 2
Polydispersity index.
Polydispersity index

Type of dispersion

0-0.05
0.05-0.08
0.08-0.7
> 0.7

monodisperse standard
nearly monodisperse
mid rangepolydispersity
very polydisperse

Zeta potential
Zeta potential is a measure of surface charge. It can
be measured by using additional electrode in the particle
size equipment (Shankar et al., 2010).
Microscopy studies
Scanning
electron
microscopy
(SEM)
and
transmission electron microscopy (TEM) can be used to
study the microscopic aspects of the drug, nanosponges
and the product (drug/nanosponges complex). The
difference in crystallization state of the raw materials
and the product seen under electron microscope indicates
the formation of the inclusion complexes, even if there is
a clear difference in crystallization state of the raw
material and the product obtained by co-precipitation
(Shankar et al., 2010; Ramnik et al., 2010, Sinha et al.,
2005; Glomot et al., 1988).

Thin Layer Chromatography

In Thin Layer Chromatography, the Rf values of a
drug molecule diminishes to considerable extent and this
helps in identifying the complex formation between the
drug and nanosponges (Ramnik et al., 2010 and Bekers
et al 1991). Inclusion complexation between guest and
host molecules is a reversible process. Consequently, the
complex may separate completely in guest and host
molecules during the chromatographic process and only
the spots of the guest and host molecules are found on
the TLC-plate (Aithal et al., 1995).

Infra-Red spectroscopy
Infra-Red spectroscopy is used to estimate the
interaction between nanosponges and the drug molecules
in the solid state.
Nanosponge bands often change only slightly upon
complex formation and if the fraction of the guest
molecules encapsulated in the complex is less than 25%,
bands which could be assigned to the included part of the
guest molecules are easily masked by the bands of the
spectrum of nanosponges (Uekama et al., 1982; Uekama
et al., 1983). The technique is not generally suitable to
detect the inclusion complexes and is less clarifying than
other methods (Ramnik et al., 2010).

1938

The application of the Infra-red spectroscopy is

limited to the drugs having some characteristic bands,
such as carbonyl or sulfonyl groups. Infrared spectral
studies give information regarding the involvement of
hydrogen in various functional groups. This generally
shifts the absorbance bands to the lower frequency,
increases the intensity and widens the band caused by
stretching vibration of the group involved in the
formation of the hydrogen bonds. Hydrogen bond at the
hydroxyl group causes the largest shift of the stretching
vibration band (Ramnik et al., 2010).

Thermo-analytical methods
Thermo-analytical methods (Duchene, 1988; Erden,
1988) determine whether the drug substance undergoes
some change before the thermal degradation of the
nanosponges. The change of the drug substance may be
melting, evaporation, decomposition, oxidation or
polymorphic transition. The change of the drug
substance indicates the complex formation. The thermo
gram obtained by DTA and DSC can be observed for
broadening, shifting and appearance of new peaks or
disappearance of certain peaks. Changes in the weight
loss also can provide supporting evidence for the
formation of inclusion complexes (Ramnik et al., 2010).
The nature of the drug and cyclodextrin used and method
of preparation of complex have been found to influence
the above finding considerably. If the interaction
between the drug and the excipient is weak, the shift in
the endothermic peak is very small.

X-ray diffractiometry and single crystal

X-ray structure analysis
Powder X-ray diffractiometry can be used to detect
inclusion complexation in the solid state. When the drug
molecule is liquid since liquid have no diffraction pattern
of their own, then the diffraction pattern of a newly
formed substance clearly differs from that of
uncomplexed nanosponges. This difference of diffraction
pattern indicates the complex formation. When the drug
compound is a solid substance, a comparison has to be
made between the diffractogram of the assumed complex
and that of the mechanical mixture of the drug and
polymer molecules (Ramnik et al., 2010).
A diffraction pattern of a physical mixture is often the
sum of those of each component, while the diffraction
pattern of complexes are apparently different from each
constituent and lead to a new solid phase with different
diffractograms.
Diffraction peaks for a mixture of
compounds are useful in determining the chemical
decomposition and complex formation (Ramnik et al.,
2010).
The complex formation of drug with nanosponges
alters the diffraction patterns and also changes the
crystalline nature of the drug. The complex formation
leads to the sharpening of the existing peaks, appearance
of a few new peaks and shifting of certain peaks (Ramnik
et al., 2010).

Int J Pharm Sci Nanotech

Vol 6;Issue 1April June 2013

Single crystal X-ray structure analysis

This method used to determine the detailed inclusion
structure and mode of interaction. The interaction
between the host and guest molecules can be identified
and the precise geometrical relationship can be
established. This information obtained during the
analysis lead to know about the formation of inclusion
complexes (Ramnik et al., 2010; Tayade et al., 2006;
Jadhav et al., 2008).

Loading efficiency
The loading efficiency of nanosponges can be
determined by the quantitative estimation of drug loaded
into nanosponges by UV spectrophotometer & HPLC
methods.

In-vitro drug release study

Drug release from the Nanosponges can be measured
across the dialysis membrane using Franz Diffusion cell
with a diffusional area of 2.26 cm2 and receptor volume of
11ml. The dialysis membrane soaked in receptor medium
for 8 hrs is used as a barrier between the donor and
receptor compartment. A one gram nanosponge was
placed on the membrane surface in the donor
compartment that was sealed from the atmosphere with
aluminium foil. The receptor compartment was filled
with 11ml of phosphate buffer of pH 6.8 (skin pH).During
the experiment, the solution of receptor side
compartment was kept at 370.5oc and stirred at 100
rpm with Teflon-coated magnetic stirring bars. Aliquots
were collected from the receptor compartment at
designated time intervals and replaced by the same
volume of fresh receptor solution to maintain sink
condition and constant volume. The sample was analysed
using UV spectrophotometer (Renuka et al., 2010).
Drug release kinetics
To investigate the mechanism of drug release from the
Nanosponge the release data was analysed using Zero
order, First order, Higuchi, Peppas, Hixon Crowell,
Kopcha and Makoid-Banakar models. The data can be
analysed using graph pad prism software. The software
estimates the parameters of a non-linear function that
provides the closest fit between experimental
observations and non-linear function (Renuka et al.,
2010). The mathematical expressions that describe the
dissolution curves are summarized in table3 (Renuka et
al., 2010)
TABLE 3
The mathematical expressions of dissolution curves.
Model

Zero order
Higuchi model
Korsemeyerpeppas model
Kopcha model
Makoid-bankar model

Equation

Qt = Q0 + K0 t
Qt = Q0 + KH t1/2
Qt = KKPtn
Qt= At1/2 + Bt
Qt= KMBtn e(-et)

1939

Bolmal et al: Recent Advances in Nanosponges as Drug Delivery System

TABLE 4
Biopharmaceutical Classification System Class II drugs.

Applications of Nanosponges
Nanosponges for drug delivery

Categery

Because of their nanoporous structure, nanosponges

can advantageously carry water insoluble drugs
(Biopharmaceutical Classification System class-II drugs).
These complexes can be used to increase the dissolution
rate, solubility and stability of drugs, to mask unpleasant
flavours and to convert liquid substances to solids. Cyclodextrin based nanosponges are reported to deliver
the drug to the target site three to five times more
effectively than direct injection (David F, 2011).
Drugs which are particularly critical for formulation
in terms of their solubility can be successfully delivered
by loading into the nanosponges. List of some BCS Class
II drugs that can be developed as nanosponges are given
in Table 4 (Leslie et al., 2007).
The nanosponges are solid in nature and can be
formulated as Oral, Parenteral, Topical or Inhalation
dosage forms. For the oral administration, the complexes
may be dispersed in a matrix of excipients, diluents,
lubricants and anticaking agents suitable for the
preparation of capsules or tablets (Jenny et al., 2011). For
the parenteral administration the complex may be simply
carried in sterile water, saline or other aqueous solutions.
For topical administration they can be effectively
incorporated into topical hydrogel (Renuka et al., 2011;
Renuka et al., 2011). The nanosponges used in the
formulation of some drugs are provided in the Table 5.

Antianxiety drug
Antiarrhythmic
agent
Antibiotics
Anticoagulant
Anticonvulsants
Antidiabetics
Antiepileptic
Antifungal agents
Antihelmintics
Antihistamine
Antihyperlipidemics
Antihypertensive
Antineoplastic
agents
Antioxidants
Antipsychotic drugs
Antiretrovirals
Antiulcer drugs
Cardiac drugs
Diuretics
Immunosupressants
NSAIDs

Steroids
Miscellaneous

Drug

Lorazepam
Amiodarone hydrochloride
Azithromycin, Ciprofloxacin,
Erythromycin, Ofloxacin,
Sulfamethoxazole
Warfarin,
Felbamate, Carbamazepine,
Clonazepam, Oxycarbazepine,
Primidone
Glibenclamide, Glipizide, Troglitazone
Phenytoin
Econazole nitrate, Griseofulvin,
Itraconazole,
Ketoconazole,Lansoprazole,Vericonazole
Albendazole, Mebendazole, Praziquantel
Terfenadine
Lovastatin, Atorvastatin, Fenofibrate
Felodipine, Nicardipine, Nifedipine,
Nisoldipine
Camptothecin, Docetaxel, Etoposide,
Exemestane, Flutamide,
Irinotecan, Paclitaxel, Raloxifene,
Tamoxifen, Temozolamide, Topotecan
Resveratrol
Chlorpromazine Hydrochloride
Indinavir, Nelfinavir, Ritonavir,
Saquinavir
Lansoprazole, Omeprazole
Carvedilol, Digoxin, Talinolol
Chlorthalidone, Spironolactone
Gastroprokinetic agent Cisapride
Cyclosporine, Sirolimus, Tacrolimus
Dapsone, Diclofenac, Diflunisal,
Etodolac, Etoricoxib, Flurbiprofen,
Ibuprofen, Indomethacin, Ketoprofen,
Mefenamic acid, Naproxen, Nimesulide,
Oxaprozin,Piroxicam,
Danazol, Dexamethazone,
Atovaquone, Melarsoprol,
Phenazopyridine, Ziprasidone,

TABLE 5
Examples of nanosponges.
Drug

Nanosponge vehicle

Indication

Antisense
Oligonucleotides
(Isabelle et al., 1999)

Sodium alginate
Poly L-lysine

Bovine serum albumin

(Swaminathan et al.,
2010)

Cyclodextrin based poly Protein suppliment

(amidoamine)

Camptothecin (Shankar
et al.,2010; Rosalba et
al., 2011)

-Cyclodextrin

Dexamethasone
(Lala et al., 2011)

In vitro / in vivo /
Mathematical Model

Pharmacokinetic
studies

Mice

Drug release study,

Stability study

In-vitro release

Cancer

Haemolytic activity
Cytotoxicty

Diluted blood HT-29 cell

line

-Cyclodextrin

Brain tumors

Drug release
Experiment

Dialysis bag
technique in vitro

Econazole nitrate
(Renuka
et al.,2011)

Ethyl cellulose
Polyvinyl alcohol

Antifungal

Irritation study

Rat

Itraconazole (Shankar
et al., 2007)

-Cyclodextrin &
copolyvidonum

Antifungal

Saturation solubility
study

Higuchi Model

Cancer

Bio- availability
Cytotoxicty

Sprague Dawley rats

MCF7 cell line

Paclitaxel (Torne
-Cyclodextrin
et al.,2010; Ansari et al.,
2011)

Cancer therapy
Viral infections
Pathologic disorders

Study

modulation and
Stability

Table 5 Contd

1940

Int J Pharm Sci Nanotech

Vol 6;Issue 1April June 2013

Drug

Nanosponge vehicle

Resveratrol (Khalid et
al., 2011)

-Cyclodextrin

Tamoxifen (Jenny
et al., 2011)
Temozolamid (William
et al., 2011)

-Cyclodextrin

In vitro / in vivo /
Mathematical Model

Indication

Study

Inflammation,
Cardiovascular
diseases, Dermatitis,
Gonorrhea, Fever and
Hyperlipidemia
Cytotoxicty
Breast cancer

Accumulation of drug in
the buccal mucosa of rabbit
Ex-Vivo Study
Permeation study

HCPC-I cell line

Rabbit buccal
mucosa
Pig skin

Cytotoxicty

MCF-7 cell line

Drug release study

In vitro and in vivo

studies

Poly
Brain tumors
(valerolactoneallylvaler
olactone) and poly
(valerolactoneallylvaler
olactoneoxepanedione)

Nanosponges as a carrier for biocatalysts

Nanosponges act as carriers in the delivery of
enzymes, proteins, vaccines and antibodies. Many
industrial processes involving chemical transformation
are associated with operational disadvantages. Nonspecific reactions lead to low yields, and the frequent
need to operate at high temperatures and pressures
requires consumption of large amounts of energy, and
very large amounts of cooling water in the down-stream
process. All these drawbacks can be eliminated or
significantly reduced by using enzymes as biocatalysts.
These enzymes operate under mild reaction conditions,
have high reaction speed, and are highly specific. They
have a beneficial effect on the environment because they
reduce energy consumption and reduce production of
pollutants. Developments in genetic engineering have
increased the stability, economy, specificity of enzymes
and number of their industrial applications is continually
increasing.
Examples. Examples of industrially useful enzymes
include alpha amylase, trypsin, cellulase and pectinase
for fruit juice clarification processes, ligninase to break
down lignin, lipase in the detergent industry and
biodiesel production, etc. The catalytic activity of enzyme
depends mainly on the correct orientation of the active
site (Amber et al., 2008).
Proteins, peptides, enzymes and derivatives thereof
also can be used in the biomedical and therapeutic field.
Proteolytic enzymes can be used to treat cancer or type I
mucopolysaccharidosis, while DNA and oligonucleotides
are used in gene therapy. The administration of these
molecules presents various problems and limitations.
Most protein drugs are poorly absorbed through the
biological membranes due to the some factors such as
large molecular size, hydrophilic nature, degree of
ionization, high surface charge, chemical and enzymatic
instability and low permeability through mucous
membranes. Following intravenous administration,
protein molecules may be rapidly cleared from blood,
bind to plasma proteins, and sensitive towards
Proteolytic
enzymes.
With
oral
administration
bioavailability is the problem. Various approaches exist
for therapeutic use, such as increasing the dose or using
absorption promoters, which can cause toxicity problems
(Amber et al., 2008).

A number of systems for carrying enzymes and

proteins have been developed, such as nano and micro
particles, liposomes and hydrogels. Carriage in a
particular system can protect proteins from breakdown,
modify their pharmacokinetics and improve their
stability in vivo. Now, it has been found that cyclodextrin
based nanosponges are particularly suitable carrier to
adsorb
proteins,
enzymes,
antibodies
and
macromolecules. In particular when enzymes are used, it
is possible to maintain their activity, efficiency, prolong
their operation and extends the pH and temperature
range of activity and allows the conduct of continuous
flow processes. Moreover, proteins and other
macromolecules can be carried by adsorbing or
encapsulating them in cyclodextrin nanosponges (Amber
et al., 2008).
Cancer Therapy

Nanosponges Carrying Anticancer Drugs Effectively

Slow Tumour Growth
Researchers at Vanderbilt University have developed
nanosponges which can be used as a delivery system for
anticancer drugs to tumors. They claim that the method
is three to five times more effective at reducing tumur
growth than direct injection of the drugs. The tiny
nanosponges are filled with a drug load and expose a
targeting peptide that binds to radiation-induced cell
surface receptors on the tumur. When the sponges
encounter tumur cells they stick to the surface and are
triggered to release their cargo. Benefits of targeted drug
delivery include more effective treatment at the same
dose and fewer side-effects. Studies so far have been
carried out in animals with paclitaxel as the sponge load.
Camptothecin, a plant alkaloid and a potent antitumor
agent, has a limited therapeutic utility because of its
poor aqueous solubility, lactone ring instability and
serious side effects. Cyclodextrin-based nanosponges are
a novel class of cross-linked derivatives of cyclodextrin.
They have been used to increase the solubility of poorly
soluble actives, to protect the labile groups and control
the release. This study aimed at formulating complexes
of Camptothecin with cyclodextrin based nanosponges
(Swaminathan et al., 2010).

Bolmal et al: Recent Advances in Nanosponges as Drug Delivery System

Treatment for Fungal Infections

Econazole nitrate, an antifungal used topically to

relive the symptoms of superficial candidiasis,
dermatophytosis, versicolor and skin infections available
in cream, ointment, lotion and solution. Adsorption is not
significant when econazole nitrate is applied to skin and
required high concentration of active agents to be
incorporated for effective therapy. Thus Econazole
nitrate nanosponges were fabricated by emulsion solvent
diffusion method and these nanosponges were loaded in
hydrogel as a local depot for sustained drug release
(Sharma et al., 2011).
Itraconazole is a BCS class-II drug that has a
dissolution rate limited poor bioavailability. Rationale of
the work was to enhance the solubility of itraconazole so
that the bioavailability problem was solved. In this
nanosponges of cyclodextrin cross linked with
carbonate bonds were prepared and loaded with
itraconazole so that its solubility was increased.
(Swaminathan et al., 2007)

Nanosponges in Proteins Delivery

Bovine serum albumin (BSA) protein in solution is not
stable;it is stored in lyophilized state. However proteins
can reversibly denatured on lyophilisation and adopts
conformation markedly different from native structure.
Major drawback in protein formulation and development
is to maintain its native structure during processing and
long term storage. In the nanosponges based approach
protein like BSA are encapsulated in swell able
cyclodextrin based poly (amidoamine) nanosponges to
increase the stability of proteins (Swaminathan et al.,
2010).
Other applications of Nanosponges

Purification of water
Cyclodextrin Nanosponges can be used for the
removal of organic pollutants from water. -Cyclodextrin
nanosponges are completely insoluble in water, have the
property of encapsulating organic pollutants from water.
Ceramic porous filters can be impregnated with these
Nanosponges resulting in hybrid organic/inorganic filter
modules. These hybrid filter modules were tested for the
effective purification of water, employing a variety of
water pollutants. It has been established that polycyclic
aromatic hydrocarbons (PAHs) can be removed very
efficiently (more than 95%). Representatives of the
pollutant group of trihalogenmethanes (THMs),
monoaromatic hydrocarbons (BTX), and pesticides
(simazine) can also be removed (>80%) (Arkas et al.,
2006).
Nanosponges based on cyclodextrin can strongly bind
organic molecules and remove them from water even at
very low concentrations (Trotta et al., 2003).

Encapsulation of gases
Cyclodextrin based carbonate nanosponges were used
to form inclusion complexes with three different gases i.e.
1-methylcyclopropene, oxygen and carbon dioxide. The

1941

complexation of oxygen or carbon dioxide could be useful

for many biomedical applications. In particular the
oxygen-filled nanosponges could supply oxygen to the
hypoxic tissues which are present in various diseases
(Trotta et al., 2011).

Bio medical Applications

The oxygen-filled Nanosponges could supply oxygen
to the hypoxic tissues which are present in various
diseases (Cavalli et al., 2010).
Nanosponges can selectively soak up biomarkers for
the diagnosis. One study concluded that Nanosponges
can harvest rare cancer marker from blood (Longo et al.,
2011).
Nanosponges can be used as carrier for gases like
oxygen and carbon dioxide.

Analytical Applications
The Micro porous hyper cross linked Nanosponges
have been used in selective separation of inorganic
electrolytes by size exclusion chromatography. The three
dimensional nanosponges will play important role in the
fractionalization of peptides for proteomic applications
(Wong et al., 2009).

Food Industry
Nanosponges are useful for elimination of bitter
components from grape fruit juice by selective
combination of polymer and cross linker.

Nanosponges forStorage of Hydrogen

Hydrogen is
considered
as
an alternative
energy for the future, but one of the problems to be
solved before it achieves the versatility of other fuel
sources as oil is how to store it. Recent studies claim
to find materials that could act as sponges that
absorb hydrogen and store it until ready to use. But until
now had not found a material with the capability to
store hydrogen
under
the
necessary pressure and
temperature.
A team of scientists from the Universities of
Newcastle and Liverpool have discovered a new class of
materials which composed of long carbon chains linked
by metal atoms. To crystallize, these molecules form
cavities that are less than a nanometer, which are
connected by windows that are even smaller than a
molecule of hydrogen.
While these cavities are filled, hydrogen fits through
the windows, because the carbon chains are flexible. But
once filled the cavities, the chains lose their flexibility,
thus closing the windows. Consequently, it can be
loading
the
high-pressure hydrogen gas,
and
when pressure levels drop, forming a sort of molecular
size seal.
Although so far the materials created by this team of
scientists do not have enough capacity for most
applications that use fuel cells, their work represents a
new approach to the problem, and nanosponges could
potentially have a key role in the hydrogen storage
system.

1942

Nanosponges for Intelligent Agriculture

Plants that grow more have a better appearance.

What counts is not just the climate, but technology. This
is so for functionalized nanosponges (FNS), an
agricultural invention that allows plants to grow more
and improve their appearance by feeding them with an
optimal dosage of micro-nutrients and active ingredients
that are necessary for healthy growth. Another notable
advantage is that nanosponges allow a significant
reduction in the use of herbicides and fertilizers, thereby
increasing productivity and improving both the
environmental and cultivation quality levels.
Nano-sponges are porous macro-molecules with nanocavities (hence the name) synthesised using a completely
natural product: starch. Nutritive substances (such as
iron and zinc), or active ingredients, are encapsulated in
the nano-cavities during the synthesis process. One of
the big advantages of this innovative product is the
possibility of making ad-hoc formulations for different
types of applications.
The nutritive substances incorporated in the
nanosponges are dosed and fed to the plants in a very
precise manner, drop by drop, thereby optimising
photosynthesis. The significant reduction in the use of
fertilisers makes their cultivation similar to that of
organic products, although production levels are much
higher. This means lower production costs and access to
healthier food for many more people.
For example, FNSs with iron solve one of the most
common problems for plants: iron chlorosis (yellowing of
the leaves), thereby allowing a more efficient
photosynthesis conversion and higher plant growth rate
(with a production yield up to 20% or more of the dry
weight), compared to plants treated with products that
are currently on the market. Also, flowers that are cut off
have a significantly longer duration in terms of their
appearance compared to those treated with products that
are currently on the market.

Nanosponge in Oil Cleaning

Nanotech allows for the creation of new materials
with unique and enhanced properties, and has specific
implications for the electronics and biomedical
industries.
One of the latest nanotech discoveries came through
researchers at Rice University and Penn State. They
found that adding boron to carbon during nanotube
construction creates spongy blocks that have amazing oil
absorbing properties.
The nanosponges are extremely hydrophobic, giving it
the natural tendency to float on water and not absorb it
even when submerged. It is also ferromagnetic, meaning
it can be controlled or retrieved using a magnet. The
density of the material is extremely low, making the
available volume for oil uptake very high. Not only can it
soak up over 100 times its weight in oil as it floats on the
water, but it can store the oil for later retrieval. The oil
can then be squeezed out or burned off, allowing the
sponge to be reused. The researchers also tested the

Int J Pharm Sci Nanotech

Vol 6;Issue 1April June 2013

sponge's robustness and reusability in the lab - it

maintained elasticity even after 10,000 compressions.
Safe to say, this material has tremendous power as an
agent for surface oil clean-up.
Conclusions
From the above study it is concluded that the
Nanosponges have the ability to include either lipophilic
or hydrophilic drugs and release them in a controlled and
predictable manner at the target site. Nanosponges can
be incorporated into a formulated product such as a gel,
lotions, cream, ointments, liquid or powder. This
technology offers entrapment of ingredients and thus
reduced side effects, improved stability, increases
elegance
and
enhanced
formulation
flexibility.
Nanosponges can be effectively incorporated into topical
drug delivery system for retention of dosage form on
skin, and also use for oral delivery of drugs using
bioerodiblepolymers, especially for colon specific delivery
and controlled release drug delivery system thus
improving patient compliance by providing site specific
drug delivery system and prolonging dosage intervals.

Future Opportunities and Challenges

Nanoparticles and nanoformulations have already
been applied as drug delivery systems with great success;
and nanoparticulate drug delivery systems have still
greater potential for many applications, including antitumour, gene, AIDS and radiotherapy in the delivery of
proteins, antibiotics, virostatics, and vaccines as vesicles
to pass the blood - brain barrier.
Nanoparticles provide massive advantages regarding
drug targeting, delivery, and release along with their
additional potential to combine diagnosis and therapy,
emerged as one of the major tools in nanomedicine. The
main goals are to improve their stability in the biological
environment, to mediate the bio-distribution of active
compounds, improve drug loading, targeting, transport,
release, and interaction with biological barriers. The
cytotoxicity of nanoparticles or their degradation
products remains a major problem, and improvements in
biocompatibility obviously are a main concern of future
research.
There are many technological challenges to be met, in
developing the following techniques:
Nano-drug delivery systems that deliver large but
highly localized quantities of drugs to specific areas
to be released in controlled ways;
Controllable release profiles, especially for sensitive
drugs;
Materials for nanoparticles that are biocompatible
and biodegradable;
Architectures / structures, such as bio mimetic
polymers, nanotubes;
Technologies for self-assembly;
Functions (active drug targeting, on-command
delivery,
intelligent
drug
release
devices/
bioresponsive triggered systems, self-regulated

Bolmal et al: Recent Advances in Nanosponges as Drug Delivery System

delivery systems, systems interacting with the body,

smart delivery);
Virus-like systems for intracellular delivery;
Nanoparticles to improve devices such as
implantable devices/nanochips for nanoparticle
release, or multi reservoir drug delivery-chips;
Nanoparticles for tissue engineering e.g. for the
delivery of cytokines to control cellular growth and
differentiation, and stimulate regeneration or for
coating
implants
with
nanoparticles
in
biodegradable polymer layers for sustained release;

References
Aithal KS, Udupa N and Sreenivassan KK (1995). Physicochemical
properties of drug-cyclodextrin complexes. Indian Drugs 32: 293305.
Amber V, Shailendra S and Swarnalatha S (2008). Cyclodextrin
based
novel
drug
delivery
systems.
J
InclPhenomMacrocyclChem 62: 23-42.
Andrea M, Franca C, Luciana M, Fabio G, Giuseppina R, Francesco
T, Barbara R, Aldo Fand Giovanni G (2011). HR MAS NMR,
powder XRD andraman spectroscopy study of inclusion
J
phenomena
111
in
CD
nanosponges.
InclPhenomMacrocyclChem 69: 403-409.
Ansari KA, Torne SJ, Vavia PR, Trotta Fand Cavalli R (2011).
Paclitaxel loaded nanosponges: in-vitro characterization and
cytotoxicity study on MCF-7 cell line culture. Curr Drug Deliv 8:
194- 202.
Arkas M, Allabashi R, Tsiourvas D, Mattausch EM and Perfler R
(2006). Organic/inorganic hybrid filters based on dendritic and
cyclodextrin "nanosponges" for the removal of organic pollutants
from water. Environ SciTechnol 40: 2771-2777.
Arun R, Ashokkumar CK and Sravanthi VVNSS (2008).
Cyclodextrins as drug carrier Molecule: A Review. Sci Pharm 76:
567-598
Bekers O, Uijtendaal E.V, Beijnen J.H, Bult A and W.J.M (1991)..
Underberg.Cyclodextrinsinthe pharmaceutical field. Drug Dev.
Ind. Pharm. 17: 1503-1549.
Cavalli R, Trotta F and Tumitti V (2006). Cyclodextrin based
nanosponges for drug delivery. J. Inclphenommacrocyl chem. 56:
209-13.
Cavalli R, Akhter AK, Bisazza A, Giustetto P, Trotta F and Vavia P
(2010). Nanosponge formulations as oxygen delivery systems.Int
J Pharm 402: 254-257.
David F. Nanosponge drug delivery system more effective than
direct injection.www.physorg.com 01.06.2010, accessed on
20.12.2011.
DeQuan L and Min M (2000). Nanosponges for water purification.
Clean products and processes 2: 112-116.
Di Nardo G, Roggero C, Campolongo S, Valetti F, Trotta F and
Gilardi G (2009). Catalytic properties of catechol 1,2dioxygenase from Acinetobacterradioresistens S13 immobilized
on nanosponges. Dalton Trans 33: 6507-6512.
Duchene D, Vaution C and Glomot F (1998). Cyclodextrin, Their
Value in pharmaceutical Technology. Drug DevInd Pharm 12:
2193-2215.
Duchene D, VautionC and Glomot F (1988).Cyclodextrin, Their
Value in pharmaceutical Technology. Drug Dev. Ind. Pharm 12:
2193-2215.
Edward C and David A. Tanner (2010). Characterisation of Porous
Silicon NanospongeParticles. Department of Manufacturing and
Operations Engineering and Materials and Surface Science
Institute, University of Limerick, Ireland.
Erden N and Celebi N (1988). A study of the inclusion complex of
Naproxen with - cyclodextrin. Int. J. Pharm. 48: 83-89.

1943

Eva Harth (2011). Nanomedicine: Development of Nanosponges as

superior sustain delivery systems of diverse biological cargos.
Department of Chemistry, Vanderbilt University, USA.
Fouda MMG, KnitellD,HiplerU.C,Elsner P and Schollmey E (1995).
Antimycotic influence of -cyclodextrin complexesIn vitro
measurements using laser nephelometry in microtiter plates.
Int. J. Pharm. 311: 113-121.
Glomot
F,
BenkerrourL,Duchene
D
and
M.C
(1988).
Poelman.Improvement in availability and stability of a
dermocorticoid by inclusion in -cyclodextrin. Int. J. Pharm. 46:
49- 55.
Gu H, Zheng R., Liu H, Zhang X and Xu B (2005). Direct Synthesis
of a Bimodal Nanosponge Based on FePt and ZnS. Small 2005;1:
402406. DOI: 10.1002/smll.200400106.
Isabelle A, Christine V, Helene C, Elias F and Patrick C (1999).
Spongelike Alginate Nanoparticles as a new potential system for
the delivery of Antisense Oligonucleotides. Antisense and
Nucleic Acid Drug Development 9: 301-312.
Jadhav GS and Vavia PR (2008)..Physicochemical, in silico and in
vivo evaluation of a Danazol -cyclodextrin complex. Int. J.
Pharm. 352: 5-1696(8): 2018-2028(2007).
Jenny A, Merima P, Alberto F and Francesco T (2011). Role of cyclodextrinnanosponges in polypropylene photooxidation.
Carbohydrate Polymers 86: 127 135.
Khalid AA, Pradeep RV, Francesco T and Roberta C (2011).
Cyclodextrin-based nanosponges for delivery of Resveratrol: In
Vitro characterisation, stability, cytotoxicity and permeation
Study AAPS. PharmSciTech 12: 279-286.
Khopade AJ, Jain S and Jain NK (1996). The Microsponge.
Eastern Pharmacist;49-53.
Lala R, Thorat A and Gargote C (2011). Current trends in cyclodextrin based drug delivery systems. Int J Res Ayur Pharm
2: 1520-1526.
Leslie Z. Benet. BCS and BDDCS (2007). Bioavailability and
Bioequivalence: Focus on Physiological Factors and Variability.
Department of biopharmaceutical sciences, University of
California, San Francisco, USA.
Liang L, De-Pei L and Chih-Chuan L (2002). Optimizing the delivery
systems of chimeric RNA . DNA oligonucleotides beyond general
oligonucleotide transfer. Eur. J. Biochem 269: 57535758.
Longo C, Gambara G, Espina V, LuchiniA,Bishop B, Patanarut AS,
Petricoin EF 3rd, Beretti F, Ferrari B, Garaci E, De Pol A,
Pellacani G and Liotta LA (2011;). A novel biomarker harvesting
nanotechnology identifies Bak as a candidate melanoma
biomarker in serum. ExpDermatol. 20: 29-34.
Nilesh J, Ruchi J, Navneet T, Brham P, Gupta, Deepak K, Jeetendra
B and Surendra J (2010). Nanotechnology: A Safe And Effective
Drug Delivery System. Asian J Phar Cli Res 3: 159-165.
Noriaki F, Seiji I and Saburo N (2008). Advances in physical
chemistry and pharmaceutical applications of cyclodextrins.
Pure ApplChem 80: 1511-1524.
Marzouqi A.H.A, Shehatta I, Jobe B and Dowaidar A (2006). Phase
solubility and inclusion complex of Itraconazole with cyclodextrin using supercritical carbon dioxide. J Pharm Sci 95:
292-304.
Patel E. K and Oswal R.J (2012).Nanosponge and Microsponges: A
Novel Drug Delivery System.IJRP 2 ISSN: 2231-2781
Patel G and Patel JK (2008).Use of a Microsponge in Drug Delivery
Systems.Pharmaceutical processing 158.
Rajeswari C, Alka A, Javed A and Khar R K (2005). Cyclodextrins
in drug delivery: an update review. AAPS pharmSciTech 6:
E329-E357.
Ramnik S, Nitin B, Jyotsana M and Horemat SN (2010).
Characterization of Cyclodextrin Inclusion complexes A
Review. J Pharm SciTech 2: 171-183.
Renuka S and Kamla P (2011). Polymeric nanosponges as an
alternative carrier for improved retention of econazole nitrate
onto the skin through topicalhydrogel formulation. Pharm
DevTechnol 16: 367-376.

1944

Renuka S, Roderick BW and Kamla P (2011). Evaluation of the

kinetics and mechanism of drug release from Econazole Nitrate
nanosponge loaded carbapol hydrogel. Ind J ParmEduRes 45:
25-31.

RiBeiroL.S.S, FalcaoA.C, Patricio J.A.B, Ferreira D.C and Veiga

F.J.B (2007). Cyclodextrin multicomponent complexation and
controlledrelease delivery strategies to optimize the oral
bioavailability of Vinpocetine. J. Pharm. Sci. 6: 2018-28.
Rosalba M, Roberta C, Roberto F, Chiara D, Piergiorgio P, Leigh E,
Li S and Roberto P (2011). Antitumor activity of nanospongeencapsulated Camptotechin in human prostate tumors. Cancer
Res 71: 4431.
SelvamuthukumarS,SingireddyA,Krishnamoorthy K and Rajappan
M (2012). Nanosponges: A Novel Class of Drug Delivery System
Review. J Pharm PharmaceutSci 15(1): 103 - 111,
Shankar S, Linda P, Loredana S, Francesco T, Pradeep V, Dino A,
Michele T, Gianpaolo Z and Roberta C (2010). Cyclodextrinbased
nanosponges
encapsulating
camptothecin:
Physicochemical characterization, stability and cytotoxicity. Eur
J Pharm Biopharm 74: 193-201.
Shankar S, Vavia PR, Francesco T and Satyen T (2007;).
Formulation of Betacyclodextrin based nanosponges of
Itraconazole. J InclPhenomMacrocyclChem 57: 8994.
Sharma R, Roderick B and Pathak K (2011). Evaluation of kinetics
and mechanism of drug release from Econazole nitrate
Nanosponges loaded carbopol Hydrogel. Indian JofPharmaEdu
and research 45: 25-31.
Sinha V.R, Anitha R, Ghosh S, Nanda A and Kumria R (2005).
Complexation of Celecoxib with -cyclodextrin: Characterization
of the interaction in solution and in solid state. J. Pharm. Sci.
94: 676-687
Swaminathan S, Cavalli R, Trotta F and Vavia PR (2007).
Formulation of betacyclodextrin based nanosponges of
itraconazole. J. Incl. Phemon. Macrocycl.Chem 57: 89-94.
Swaminathan S, Cavalli R, Trotta F and Vavia PR (2010). In vitro
release modulation and conformational stabilization of a model
protein
using
swellablepolyamidoaminenanosponges
of
J.Incl.Phemon.Macrocycl.ChemDOI
cyclodextrin.
10.1007/s10847-010-9765-9.
Swaminathan S, Pastero L, Serpe L, Trotta F and Vavia P ( 2010).
Cyclodextrinbasednanosponges encapsulating camptothecin:
Physicochemical characterization, stability and cytotoxicity. Eup
J of Pharmaceutics and Biopharmaceutics 74: 193-201.
Swaminathan S, Vavia P, Trotta F and Torne S (2007). Formulation
of beta cyclodextrin based nanosponges of Itraconazole. J.
Incl.Phemon.Macrocyl.chem 57: 89-94
Tayade PT and Vavia PP (2006). Inclusion complexes of Ketoprofen
with - cyclodextrins: Oral pharmacokinetics of Ketoprofen in
human. Indian J Pharm Sci 68: 164-170.

Int J Pharm Sci Nanotech

Vol 6;Issue 1April June 2013

Tayade P.T. and Vavia P.R (2006). Inclusion complexes of

Ketoprofen with - cyclodextrins: Oral pharmacokinetics of
Ketoprofen in human. Indian J. Pharm. Sci. 68: 164-170
Torne SJ, Ansari KA, Vavia PR, Trotta F and Cavalli R ( 2010).
Enhanced oral Paclitaxel bioavailability after administration of
Paclitaxel loaded nanosponges. Drug Delivery 17: 419425.
Trotta, F, Cavalli, R, Vavia PR and Khalid A (2011). Cyclodextrin
nanosponges as effective gas carriers. J of Inclusion Phenomena
and Macrocyclic Chemistry, online first TM, 22nd Feb. DOI:
10.1007/s10847-011-9926-5.
Trotta F, Cavalli R, Tumiatti W, Zerbinati O, Rogero C and Vallero
R (2007). Ultrasound-assisted synthesis of Cyclodextrin-based
nanosponges. EP1 786 841 B1
Trotta F, Tumiatti V, Cavalli R, Rogero C, Mognetti B and Berta
G(2009). Cyclodextrin-based nanosponges as a vehicle for
Antitumoral drugs. WO 2009/003656 A1.
Trotta F and Tumiatti W (2003). Cross linked polymers based on
cyclodextrin for removing polluting agents.; WO 03/085002.
Trotta F and Cavalli R (2009). Characterization and applications of
new hyper-crosslinkedcyclode-xtrins. Composite interfaces 16:
39-48.
UekamaK,HirayamaF,Otagiri M andYamasaki M (1982). Inclusion
complexations of steroid hormones with cyclodextrins in water
and in solid phase. Int. J. Pharm. 10: 1-15.
Uekama K, Fujinaga T, Hirayama F, OtagiriM,Yamasali M,
SeoH,Hasimoto T and TsuruokaT(1983). Improvement of the
oral bioavailability of digitalis glycosides by cyclodextrin
complexation. J. Pharm. Sci.72(11): 1338-1341.
Vavia P, Swaminathan S, Trotta Fand Cavalli R (2006). Applications
of nanosponges in drug delivery. XIII International
Cyclodextrins symposium Turin 14-17.
WangL,Jiang X, XuW and Li C (2007). Complexation of Tanshinone
IIA with 2- hydroxypropyl--cyclodextrin: Effect on aqueous
solubility, dissolution rate, and intestinal absorption behavior in
rats. Int. J. Pharm. 341: 58-67.
William K, Benjamin S and Eva H (2011). Synthesis and
Characterization of Nanosponges for Drug Delivery and Cancer
Treatment. www.Vanderbilt.edu accessed on 20.12.2011.
Wolfgang S (2007). Sample preparation in Light Scattering from
Polymer Solutions and Nanoparticle Dispersions. Springer
Berlin Heidelberg GmbH & Co. K. P 43-4.
Wong VN, Fernando G, Wagner AR, Zhang J, Kinsel GR, Zauscher S
and Dyer DJ (2009). Separation of peptides with
polyionicnanosponges for MALDIMS analysis.Langmuir 25:
1459-65.
Address correspondence to: Uday B. Bolmal, Department of
Pharmaceutics, KLEUs College of Pharmacy, Belgaum- 590010,
Karnataka, India.
E-mail: udaybolmal@yahoo.co.in, Tel: +91 9945598377