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ABSTRACT
Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it
should deliver the drug in accordance with a predetermined rate and second it should release
therapeutically effective amount of drug at the site of action. Conventional dosage forms are
unable to meet these requisites. Niosomes are essentially non-ionic surfactant-based
multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed
by a membrane resulting from the organisation of surfactant macromolecules as bilayer.
Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates
imbibing or encapsulating the hydrating aqueous solution. The proposed review deals with
composition, methods of preparation, and applications of niosomes in the pharmaceutical field.
The main aim of development of niosomes is to control the release of drug in a sustained way,
modification of distribution profile of drug and for targeting the drug to the specific body site.
INTRODUCTION ADVANTAGES
Vesicular systems are a novel means of drug The application of vesicular (lipid vesicles and
delivery that can enhance bioavailability of non-ionic surfactant vesicles) systems for
encapsulated drug and provide therapeutic therapeutic purpose may offer several
activity in a controlled manner for a prolonged advantages: -
period of time. Niosomes are nonionic 1. High patient compliance in comparison
surfactant vesicles in aqueous media resulting with oily dosage forms as the vesicle
in closed bilayer structures that can be used suspension is a water–based vehicle.
as carriers of amphiphillic and lipophilic drugs 2. Accommodate drug molecules with a wide
1
.Niosomes are microscopic lamellar range of solubilities.
structures formed on admixture of non-ionic 3. The characteristics of the vesicle
surfactant of the alkyl or dialkyl polyglycerol formulation are variable and controllable.
ether class and cholesterol and the enclosed Altering vesicle composition, size,
interior usually contains a buffer solution at lamellarity, surface charge and
2
appropriate pH . In niosomes, the vesicles concentration can control the vesicle
forming amphiphile is a non-ionic surfactant characteristics.
stabilized by addition of cholesterol and small 4. The vesicles may act as a depot, releasing
amount of anionic surfactant such as dicetyl the drug in a controlled manner.
phosphate3. Non-ionic surfactants provide a 5. They are osmotically active and stable, as
few advantages over the phospholipids well as they increase the stability of
because they are more economical and are entrapped drug.
chemically more stable as they are not easily 6. Handling and storage of surfactants
hydrolysed or oxidised during storage. The requires no special conditions.
vesicular structure can be modified to provide 7. They improve oral bioavailability of poorly
sustained or controlled drug delivery thus absorbed drugs and enhance skin
enhancing efficacy of system for prolonged penetration of drugs.
periods 4. 8. They can be made to reach the site of
action by oral, parenteral as well as topical
routes.
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with non-ionic surfactants. The result of the and prolong the existence of the drug in the
coating process is a dry formulation in which systemic circulation. Niosomes were prepared
each water-soluble particle is covered with a from Span40, Span60, and Cholesterol using
thin film of dry surfactant. This preparation is reverse evaporation method. The in vitro
termed as “proniosomes”. The niosomes are release study signifies sustained release
recognized by the addition of aqueous phase profile of niosomal dispersions. Release profile
at (T > Tm) and brief agitation simultaneously. of prepared formulations has shown that more
T=Temperature. than 85.2±0.015% drug was released in 24 h
21
Tm = mean phase transition temperature . with zero-order release kinetics. The results
obtained also revealed that the types of
Sonication Method surfactant and Cholesterol content ratio
The size range of niosomes has a major effect altered the entrapment efficiency, size, and
on their in-vitro in-vivo fate. Hence, size drug release rate from niosomes23. Niosomal
reduction of niosomes is essential after formulation could be promising delivery
hydration stage. Niosomes prepared by system for gliclazide with improved
reverse phase evaporation and hand-shaking bioavailability and prolonged drug release
method are usually in micron size range (1.15 profile. Gliclazide-loaded niosomes were
and 2.75mm). By using sonication technique, formulated and evaluated for their in-vitro as
size of niosomes formed by hand shaking can well as in-vivo characteristics in an attempt to
be reduced to 100-140 nm. In this method, improve the oral bioavailability of the drug. The
average size of vesicles can be reduced by in-vitro release studies of drug from niosomes
providing high energy by sonication. This is exhibited a prolonged drug release as
24
done by exposure of multi lamellar vesicles to observed over a period of 24 hrs .
ultrasonic irradiation. Sonication method is
most widely used for producing small vesicles. Transdermal Delivery
There are two types of sonication based on Slow penetration of drug through skin is the
the use of either probe or bath ultrasonic major drawback of transdermal route of
disintegrators. The probe is employed for delivery. An increase in the penetration rate
dispersions, which require high energy in small has been achieved by transdermal delivery of
volume while bath is more suitable for large drug incorporated in niosomes. Niosomes of
22
volume . terbinafine hydrochloride was formulated by
thin film hydration method using different ratios
APPROACHES OF NIOSOMES of non-ionic surfactants (Tween 20, 40, 60,
The administration of niosomes by various and 80) and cholesterol with constant drug
routes has been reported and it is clear that concentration. Niosomal preparations were
the route is important in designing a vesicular tested for in-vitro antifungal activity using the
formulation. strain Aspergillus niger and compared with
pure drug solution (as standard). All the
Oral Route Delivery niosomal formulations showed gradual
Niosomes can be proposed as a potential oral increase in zone of inhibition due to the
delivery system for the effective delivery of controlled release of medicament. The studies
drugs. The delivery of biopharmaceuticals to revealed that gel containing total niosomes
the systemic circulation through oral possess maximum zone of inhibition values
administration is hindered by numerous (12mm) initially followed by sustained release
barriers, including pH gradients, proteolytic (12mm-16mm) compared to gel containing
enzymes and low epithelial permeability. The drug entrapped niosomes, gel containing pure
25
oral delivery of recombinant human insulin drug and marketed preparation . Proniosomal
using niosomal formulations was gels of flurbiprofen were developed using
demonstrated by a study involving different spans with and without cholesterol.
polyoxyethylene alkyl ethers based niosomes. Niosomes were formed by hydrating
Entrapment of insulin in bilayer structure of proniosomes. Results indicated that the
niosomes protected it against proteolytic entrapment efficiency followed the trend Sp 60
activity of α-chymotrypsin, trypsin and pepsin (C18)>Sp 40 (C16)>Sp 20 (C12)>Sp 80 (C18).
in vitro. Significantly higher protection activity Cholesterol increased or decreased the
was seen in Brij 92/cholesterol (7:3 molar entrapment efficiency depending on either the
ratios) in which only 26.3±3.98% of entrapped type of the surfactant used or its concentration
insulin was released during 24 h in simulated within the formulae. Increasing total lipid or
10
intestinal fluid (SIF) . Encapsulation of drug concentration also increased the
Ganciclovir in lipophilic vesicular structure may entrapment efficiency of flurbiprofen into
26
be expected to enhance the oral absorption niosomes . Benzoyl peroxide was entrapped
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into niosomes by thin film hydration technique, preserved with Span 40 niosomes .
and various process parameters were Niosomes of cisplatin were prepared using
optimized by partial factorial design. The Span 60 and cholesterol and investigated for
optimized niosomal formulation was antimetastatic activity in experimental
incorporated into HPMC K15 gel and metastatic model of B16F10 melanoma.
extensively characterized for percentage drug Treatment with niosomal cisplatin (1 mg/kg)
entrapment (PDE) and in vitro release and combination of the same with theophylline
performance. The present study demonstrated (15 mg/kg) showed significant reduction in the
prolongation of drug release, increased drug number of lung nodules as compared to
retention into skin, and improved permeation untreated control as well as free cisplatin (1
across the skin after encapsulation of benzoyl mg/kg). The treatment with activated
27
peroxide into niosomal topical gel . macrophages (activated by using Muramyl
Entrapment of drug Erythromycin into dipeptide) significantly reduced the secondary
niosomes showed prolongation of drug growth of tumor in lung. Niosomal cisplatin
release, enhanced drug retention into skin and showed a significant protection against weight
improved permeation across the skin after loss and bone marrow toxicity as compared to
28 31
encapsulation . free cisplatin .
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volume and a constant CO2 amount as C18EO6 aceclofenac. Dig J Nanomater Bios.
42
completely dissolved in supercritical CO2 . 2010; 5(1): 249-254.
9. Uchegbu IF, McCarthy D, Schatzlein
CONCLUSION A, Florence AT. Phase transitions in
The concept of incorporating the drug into aqueous dispersions of the hexadecyl
liposomes or niosomes for a better targeting of diglycerol ether (C16G2) non-ionic
the drug at appropriate tissue destination is surfactant, cholesterol and cholesteryl
widely accepted by researchers and poly-24-oxyethylene ether: vesicles,
academicians. Niosomes represent a tubules, discomes and micelles. STP
promising drug delivery module. They Pharma Sci. 1996; 6: 33–43.
presents a structure similar to liposome and 10. Pardakhty A, Varshosaz J,
hence they can represent alternative vesicular Rouholamini A. In vitro study of
systems with respect to liposomes, due to the polyoxyethylene alkyl ether niosomes
niosome ability to encapsulate different type of for delivery of insulin. Int J Pharm.
drugs within their multienvironmental structure. 2007; 328: 130–141.
The usefulness of niosomes in the delivery of 11. Muzzalupo R, Ranieri GA, La Mesa C.
proteins and biologicals can be Translational diffusion and other
unsubstantiated with a wide scope in physicochemical properties of a
encapsulating toxic drugs such as anti-cancer bolaform surfactant in solution.
drugs and anti-viral drugs. Niosomes are Langmuir. 1996; 12: 3157–3161.
thoughts to be better candidates drug delivery 12. Rentel CO, Bouwstra JA, Naisbett B,
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ophthalmic, topical, parentral, etc. 13. Azmin MN, Florence AT, Handjani-
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