A COMPREHENSIVE REVIEW ON A NEW TRENDS IN NOVEL

INSITU GELS USED IN GASTRORETENTIVE DRUG DELIVERY

SYSTEM
Dr.Shailaja Pashikanti1, Ms. Mortha Lakshmi Prasanna*
1.. Department of Pharmaceutical Technology, Associate professor of Pharmacy Sciences, Andhra University,
Visakhapatnam- 530003.
*Corresponding author: M.Lakshmi prasanna, Research scholor (part time) at Andhra university & Associate
Professor,vjsCollege Of PharmacyA U College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-
530003., India.
E-mail address: luckympharma09@gmail.com

ABSTRACT

The current review of the in situ gelling system is one of the most popular and prominent.
Shipping has huge benefits system due to many advantages such as using simple manufacturing;
improve patient compliance and comfort by reducing frequency.The drug has a unique property
of moving the left gel. Also, in situ gelling nanoemulsions provide nanosphere,microspheres and
liposomes. Disadvantages associated with conventional solution and gel systems include
accurate and easy dosing administration is overcome by using the in situ gelling system. This
overview covers definitions, types, advantages, disadvantages, polymers used and favorable
properties of polymers by preparing in situ gels coated on the substrate. Approach, application
and evaluation. Gels in situ are explained with examples.
KEY WORDS : Gel, hydrogel, gel in situ, polymer, nanoemulsion, liposomes.

INTRODUCTION
Gel is a soft, stable or solid material that consists of min two components, one of which is a
liquid, present in substantial amountsquantity [1]. Gels are an intermediate state of matter
containing both liquid and reliable ingredients (semi-solid or semi-liquid). Gels they combine the
cohesive properties of solids and diffusive transport characteristics of liquids [2]. It consists of a
three-dimensional, stable, and secure component network [3]. In gels, there is a polymer network
formed by cross-linking polymer chains using either formation covalent (chemical cross-linking)
or non-covalent bonds (physical cross-linking). Based on the nature, gels are classified into two
types (ie physical and chemical). Physical gels have weak bonds such as hydrogen, electrostatic
and Vander Waal bonds [4]. Due from the point of view of toxicity, there is increasing interest in
physically cross-linked gels – chemical gels when strong covalent bonds are formed [5].
Hydrogels are polymer chains of three-dimensional (3-D) structures. So they can be easily
molded into different sizes and shapes [6]. These hydrogels have excellent transition absorption
capability between the liquid gel and itself; it is a type of hydrophilic preparation [7]. Hydrogels
consist of crosslinks that serve to store a considerable amount of air and holds a huge amount
water and biological fluids swell. Hydrogels are also classified into two types (i.e., preformed
hydrogels and in situ gels) [8]. Preformed gels or preformed particle gels (PPG) are simple
viscous solutions that cannot undergo any modification after submission [9]. PPG is a
superabsorbent cross-linking polymer that can swell to 200 times its original size and acts as a
fluid drain compliance checking is a new process designed to overcome some distinct
shortcomings inherent in the in situ gelation system [10]. On overcome changes in gel
composition, degradation, lack of gelation time control and several weaknesses are related to
preformed gels. Still, dilution with water and has a defect in the ophthalmic dosage form,
including less accurate dose, blurred vision, tearing, etc. Before injection, preformed gels are
formed on the surface through the tank [11]. Thus, no gelatinization occurs and is needed to
consider, including pH, salinity, polyvalent ions, hydrogen sulphide, temperature and shear rate
[10]. In situ gels are solutions or suspensions that undergo gelation after reaching a specific
location due to contact with body fluids or physico-chemical changes such as pH, temperature,
ionic concentration, UV radiation, presence of specific molecules or ions, external triggers, etc.
[12]. In situ gel produces constant plasma profile of the drug in the body by prolonging the
release of the drug, that is attached and absorbed in gel form and is known to extend life
drug in the mucosa [13]. The drug delivery systems they have properties, as mentioned earlier, of
the sol-gel transition widely used for the preparation of a vehicle for the sustained administration
of a bioactive substance molecules [14]. In situ gels, potentially used for oral, buccal,
subcutaneous, transdermal, intraperitoneal, ocular, nasal, rectal, vaginal and parenteral routes
[15]. From a production point of view, less complicated and thus reduces investment and
production costs [16]. In the discovery phase, gel formulations are used to increase local and
systemic potential exposure lead compounds, which is ideal for creating animal models
different conditions quickly and cost-effectively [17]. Despite a huge variety of gels, a special
class of gels, specifically smart polymer gels, are in the focus of pharmaceutical research during
recent decades [18]. These smart polymers change their physico-chemical properties in response
to a changed environment. Recent advances have enabled gels to be used in situ changes in
physiological uniqueness [19]. Comprehensive research was performed in the design of in situ
gels, which emerged as one of the best new drug delivery systems (NDDS) [20]. In this review
they mainly focused on the introduction, advantages, disadvantages, suitable polymer properties,
approaches, applications, product evaluation and marketing of in situ gels. It also focused on
some reported studies as well as recent advances in in situ gels. The intention of writing this
review article is to describe each aspect in situ gels that have a specific property and strength
near readers contribute to research and development.
Advantages:
 reduce drug waste
 Facilitation of administration
 Administered to unconscious and elderly patients
 Facilitates prolonged or sustained release of drugs
 Enables greater patient comfort and compliance
 Due to the low dose, drug accumulation will not occur and minimize drug toxicity
 Offers greater bioavailability
 By using natural polymers it provides biocompatibility and biodegradation .
 Using synthetic polymers usually well define that can be modified to provide tolerable
degradability and functionality. T
 he drug targets mainly through the mucous membrane,for non-invasive medicine Vivo
offers essential privacy in vivo hydrophilicity increases during in vivo circulation
delivery device.
 First, it shows bio-adhesiveness to facilitate drug targeting through mucosal membranes
for non-invasive drug delivery .
 Reduce systemic drug absorption nasolacrimal duct abnormality.
  Requires high flow fluid Soluble forms of the drug are more susceptible to spoilage
There is a possibility of stability due to chemical degradation problem Eating and
drinking are restricted for several hours after implantation medicine.
 Only small doses are given Because the mechanical power is low, it can happen
prematurelybreak down.
 Mainly hydrophobic drugs, for their quantity and homogeneity
 Drug loading into hydrogels can be limited [39, 40].
Beneficial properties of polymers
An important element in in situ production and pre-production gel is a polymer. Polymer
properties are suitable for in situ gels given below [41-45]: Must match Any toxic effects should
not occur It should have good durability and optical clarity It should be pseudo-plastic
The tip must be able to attach to the tumor membrane  Must be able to reduce viscosity as it
increases at the shear level T Must be affected by the action of tears Classification of in situ
gelling polymers Depending on their origin, polymers can be classified or mechanized
jellia Gel system, according to sources on the scene divided into two types [46-50].
I. natural polymers (e.g. alginic acid, carrageenan, chitosan, guar gum, (gellan gum, pectin,
sodium hyaluronate, xanthan gum, xyloglucan, etc.)
ii. synthetic or semi-synthetic polymers (e.g. CAP, HPMC, MC, PAA,(PLGA, poloxamers)
Left-hand method The starting material "Sol" is usually an inorganic or organic metal salt
compounds such as metal alkoxides. In the traditional left hand way, undergo initial hydrolysis
and polymerization reaction or condensation to produce a colloidal suspension or solution. Full
length polymerization leads to conversion with subsequent loss of solvent from "sol" (liquid
phase) to "jelly" (solid phase) [51]. Gel preparation in situ the polymer can vary depending on
the in situ cell growth system. Polymer solutions are prepared by dissolving them as needed
polymer and copolymer in distilled water using a magnetic stirrer until the polymer is completely
dissolved. Next especially for preparing aqueous medicinal solutions prepare a polymer solution
and stir constantly until the same solution, then add buyers based on delivery system. Finally,
make the volume with distilled water [52].
In situ gel approaches
There are four general mechanisms used to initiate gel in situ biomaterial [15, 22, 34, 42, 53-55]:
A. Physiological stimuli (eg temperature and pH)
B. Physical stimulation (eg, solvent exchange or diffusion and swelling)
C. Chemical stimulation (eg enzyme, chemical, and photoinitiated).
polymerization)

A. Physiological stimulation
Based on the physiological stimuli divided into two categories:
Happens in gelation system in situ or at thermal temperature braking system In this system, there
is no external heat except body temperature must cause inflammation and show a mechanism
i. thermo-sensitive type inactive; e. g., poly-N-isopropyl acrylamide
(PNIPAAm)
ii. ii. Positive thermosensitive type, e. g., polyacrylic acid (PAA), poly
(acrylamide-co butyl methacrylate) or polyacrylamide
iii. iii. Write opposite terms; e. g. poloxamer, pluronic (poloxamer), tetronics
(poloxamines), poly (ethylene oxide)-b-poly (propylene)
oxide)-b-poly(ethylene oxide) This poly-electrolyte causes an increase in external pH
swelling hydrogels leading to their formation in situ gel - some anionic groups are used as a pH
buffering system. For example. Cellulose acetate phthalate (CAP), polyethylene glycol (PEG),
pseudo latex, methacrylic acid (PMC), carbomer and its derivatives, et al., it is also a mixture of
poly-methacrylic acid (PMA) and PEG used as a pH-sensitive system to achieve gelation. Most
of them anionic pH-sensitive polymer PAA (carbopol, carbomer) or na derivative.
B. Physical stimulation When a material absorbs water from its environment, In-situ formations
can also be desired and expanded.
Solvent exchange or diffusion This process involves solvent diffusion from the polymer solution
surrounding tissue and lead to precipitation or hardening polymer matrix. This is the most widely
used polymer This approach is N-methyl pyrrolidone. Photo-initiated polymerization This is the
most convenient and commonly used approach formation of gels in situ. Monomer or reactive
micromer solution and initiators are injected into tissue sites and applied pH control system In
this approach, pH-sensitive or pH-sensitive polymers will be used
to form a gel. All pH-sensitive polymers are acidic or basic functional groups that can be ionized
and released or accepted protons for pH changes. A large number of ionizable particles group
known as polyelectrolytes and mechanisms swelling A polar lipid or polymer swells from the
inside out and slowly drug release (ie, to form a lyotropic crystal phase structure). This is it it has
some bio-adhesive properties and is degraded enzymatically in vivo actions . For example,
Myverol 18-99 (glycerol-mono-oleate) C. Chemical reaction Chemical reactions can occur that
cause gelations in situ precipitation of inorganic solids by the following process.
Chemical polymerization of ionic compounds Ion-sensitive polymers form gels in the presence
of ions such as Na +, K +, Ca + 2 and Mg + 2. This ionic polymer undergoes a phase transition
to form a gel. Some polysaccharides belong to this class. Enzymatic polymerization or enzyme
conjugation In this approach, it is formed by gel cross-linking Enzymes are present in body
fluids and some advantages over chemical and photochemical methods and mechanism
Photo-initiated polymerization:
This is the most convenient and commonly used approach formation of gels in situ. Monomer or
reactive micromer solution and initiators are injected into the tissue area and use electromagnetic
radiation to form a gel. Usually long-wavelength ultraviolet (i.e. ketones) and visible (camphor-
quinones) and ethyl eosin) wavelength polymers are used (ie acrylates or other polymers) - not
used due to short wavelength polymers a novel approach to biologically inert, in situ gels A
variety of different systems are used to enhance drug delivery in situ cell system. This system
slows down active elimination substance in the eye and increased penetration of the cornea drug
molecules . Nanoparticles are encapsulated in the gel in situ Recently, nanoparticles have been
used to solve related problems topical formulation. For this, it represents a promising drug
operator targeting the lacrimal tissue while remaining at the application site and provide long-
term release with particle degradation or erosive drugs diffusion or a combination of the two.
Liposomes are encapsulated in a gel in situ It is also a tool for long-term drug control; in lipids
vesicles encapsulated active ingredients and transported drugs through the cornea . Movies or
online learning apps Burst applications or films are usually semi-continuous or full length size
and type intended for ophthalmic use . Nanoemulsification in situ gel Nanoemulsions are widely
used because of their intrinsic advantages high penetration into deeper layers, continuous release
medicine for the cornea and ease of sterilization .
APPLICATIONS
Oral drug delivery system gellan gum, pectin, xyloglucan etc. oral in situ gels.
The pH sensitive gels have potential applications in targeted drug delivery to certain areas of the
gastrointestinal tract (GIT) and others polymers and drugs as routes of administration have been
reported in situ gelling system.
Gellan gum
Gellan gum has a tendency to gel with temperature-dependent or induced cations. There is an in
situ gelling systembgelled solution with calcium chloride and sodium citrate complex. When
administered orally, it contains calcium ions it is released in the stomach acid environment
gelation of the gel, thus forming a gel in situ [83].
pectin
Gelation of pectin will occur in the presence of H+ ions, which is the source cation dissociation;
Calcium ions are often needed for its production gel is suitable as a vehicle for drug delivery
[22]. Primary The advantage is that it is water soluble, so no organic matter is needed solutes in
the formula. Individual cations present in the stomach When processed, make sure that the pectin
becomes a gel state oral [12]. May contain calcium ions in the form of supplements formulation
for the induction of pectin gelation. It may contain sodium citrate Add the solution above to
make a set with more add calcium ions. It is stored until it is in a liquid state ("left"). complex
breakdown in the stomach acid environment, where the release of calcium ions causes gelation
[14]. The the amount of calcium and citrate ions to be retained can be optimized liquid Before
entering the stomach, the end occurs clarity in composition.
Xyloglucan
Xyloglucan is then partially degraded by β-galactosidase products show thermal inversion
through lateral packing from the same circuit or when heated to body temperature [14].
Depending on the extent of galactose removal, the sol-gel transition the temperature also varies.
oral use Shipping uses the slowest delivery time we will offer In the gastric mucosa after the oral
cavity refrigerated xyloglucan solution [13]. Gelatinous properties of Xyloglucan Similar to
Pluronic F127, but forms a "gel" to a lesser extent concentration [12]. A readable drug delivery
system Conventional delivery systems often result in decreased bioavailability and therapeutic
effects due to tear fluid; causing dynamics rapid elimination of drugs [15]. alginic acid, gellan
gum and xyloglucan is most commonly used to deliver ocular drugs. For local Antimicrobial,
anti-inflammatory, and self-acting medications drugs used to relieve intraocular tension in
glaucoma [16]. Various coated with water-soluble polymers and pH on precipitation polymer
systems such as carbopol, HPMC, PMA-PEG [17].
alginic acid
Aqueous solutions of alginates form a gel when added Trivalent metal ions are involved in the
cooperative process and continue glucuronate residues in the α-L-glucuronic acid block of
alginate chain. Longevity of formulations containing bubbles alginic acid, based not only on the
ability to gel in the eyes, but also and mucoadhesive properties [22].
Carbopol
Known to be pH dependent, it will remain in solution at acidic pH but forms a low viscosity gel
at alkaline pH. Together Gives the viscosity of carbopol solution when reduced by HPMC acid
solution [22].
Gellan gum
There is much interest in the medicinal uses of gellan gum summarized the delivery of
ophthalmic drugs. Water solution gel in the eye a transition to a gel state due to temperature and
ions (Ca+2) in tear fluid. Medicine from this gel in situ extended due to the longer contact time
of the gel adhering to the cornea compared to conventional eye drops [10, 11].
Xyloglucan
Xyloglucan chains are hydrophilic, dense, and mucoadhesive potential, suitable candidate for
corneal augmentation while medicine stays. Take the medicine Long-term drug elimination was
obtained by attaching in situ gels formula [12].
Nasal drug delivery system
Nasal drug administration is considered an alternative way for the use of the drug system is
limited to intravenous administration. Nasal drug delivery can also provide an entry route into
the brain circulation through the blood-brain barrier (BBB) because the olfactory receptor cells
are in direct contact with the central nervous system. Because of the large absorption area and
low proteolytic activity, The nasal mucosa is considered an attractive site for delivery injection.
Nasal injections will increase and decrease patient compliance production cost compared to the
parent product. Mainly protein and peptides can deliver in this direction [23, 24].
Parenteral drug delivery system
Chitosan is a biocompatible pH-dependent cationic polymer soluble in aqueous solution, pH
above 6.2 forming a hydrated gel-like precipitate [22, 23]. The main problem Chitosan is non-
biodegradable between this slide and the same slide as the second dimension page slide fixed.
The second slide is provided with a hook. 1 gram weight on two slides for 5 minutes. Chase air
and make sure the gel film is uniform between the two slides. SCALE weight placed on the plate
attached to the pulley the time required by the upper slide to release the hook from the topper
slide is marked. Shorter distances indicate better dispersion coefficient (S) [14, 15].
M = Weight depends on the top slide
L = Length of slide page
T = the time it takes to remove the slides Increase power The meter determines the strength of
the gel and depends on it The gelling mechanism is a certain amount of "gel". In the hook, it is
prepared from the "left" shape. This is the "gel" that holds the bread it must be raised at a certain
speed, so push the probe slowly The load on the gel and the probe are measured by depth
Immersion in the surface "wind" [13, 16]. Sales ability Method 1 By placing a drop of freshly
prepared formula in the vial contains 2 ml of Stimulant Tear Fluid (STF) and label below the
time required for the result "gel" or "gel" to dissolve at pH 7.4 phosphate buffer and used to
determine compatibility polymer concentration or gel forming agent in situ system [17].
Method 2 They use water-soluble dyes such as amaranth, Congo red, blue indigo etc. Dissolve 1
g in distilled water and mix with prepared in situ gel. In vitro, potential bride formulation is
measured by placing 5 ml of gelatin solution (STF) in glass tubes and kept at temp 37 ± 0.5 ° C.
Immediately turns into a gel-like solid. In vitro, the potency of the gel is assessed by its presence
gel strength. Time for the gel to turn This is how thick the gel is. In addition, color is added to
give visuals type of gel. In vitro based on three categories
Gelation capacity was calculated [18].
+ "Let's" spread quickly after a few minutes
++ Celia appeared immediately and stayed for several hours
+++ immediately wipes up, lasts for a long time
Time
Miscibility and rheology
Monitor room (ie, 25°C) and body temperature (ie, 37 ± 0.5°C) Viscosity using a Brookfield
viscometer. Rheology was obsd due to the thicotropic nature of the gel. Gel preparation in situ
should show pseudo-plastic and Newtonian flow before and after healing process. There should
be 5-1000 m from Pas before and after arrival ("Left") and 50-50,000 m Pasdan ("coming"),
respectively. Come over In-situ formulation should be well formulated, so administration patient,
especially in ocular administration. But, this agent has blurred and impaired vision storing waste
in containers; may be due to its high viscosity difficulty in screening [119, 120]. Learn
sustainability Stability testing focuses on determining retention time and usability Proceedings of
the International Conference on Harmonization (ICH). Place the sample in an air chamber at 40
± 2 °C temperature and 75 ± 5% RH for about a month. A month, analyzed the clarity of the
sample, pH, viscosity, drug substance, rheological and in vitro dissolution. Storage the
conditions and duration of the chosen course must be sufficient covering their storage, shipment,
and further use [121, 122]. Drug withdrawal studies Medicine in vitro In vitro release assays can
be performed in an in vitro release system used a Franz diffusion cell to test continuity [44, 123].
In vivo drug release Evaluating medicine is medicine in the body in vivo). Know that time
ravages and part of the polymer if used, we can tailor medicine according to the needs of
pharmacotherapy [94, 124].
CONCLUSION
The results The use of gels in situ provides various advantages standard dosage form. The use of
biocompatible, Biodegradable and water-soluble polymers for in situ gels The formulation is
excellent and can make an excellent drug delivery system. In the new year, researchers have
been interested and there are limits provide an advanced method of drug delivery. New carrier
can add to this system to deliver sustained medicine increased and extreme. These systems are
what they are it can be administered as a solution and can gel in place Movement Finally, the gel
is easy to use and administer to the patient.
REFERENCES

1. Rogovina LZ, Vasilev WG, Braudo EE. Definition of the concept polymer gel. Polym Sci
Series C 2008; 50: 85-92.
2. Whitlock DR, Weiss L, Ambrogio LN, inventors, AOBIOME LLC, Scheduled.
Microorganisms for ammonia utilization and delivery to the digestive tract. United States Patent
US application 16/318,583; 2019.
3. Karlfors J, Edsman K, Pietersson R, Jornwing K. Rheological Evaluation of gels in situ for
ophthalmic use. Eur J Pharm Science 1998; 6:113-9.
4. Ullah F, Osman MB, Javed F, Ahmad Z, Akil HM. classification, processing and applications
of hydrogels: a review. Mater Sci Eng C 2015; 57:414–33.
5. Crini G. Recent developments in polysaccharides materials used as adsorbent in waste
treatment. Prog Polym Sci 2005; 30:38-70.
6. Kuo CK, Ma PX. Such as ionically cross-linked alginate hydrogels Scaffolding for textile
engineering: Part 1. Structure, cell velocity and mechanical properties. Biomaterials 2001;
22:511–21.
7. Peak CW, Wilker JJ, Schmidt G. A solid and flexible review hydrogel. Colloid Polym Sci
2013; 291: 2031-47.
8. Fuchs S, Shariati K, Ma M. Thyroid hydrogels and their properties biomedical applications.
Adv Health Mater 2020; 9:1901-396.
9. Zhao X, Sun X, Chang J, Bai B. gel composition and salinity concentration effect on hydrogel
dehydration uniaxial compression. J Petrol Sci Eng 2019; 182:106358.
10. Bai B, Zhou J, Yining M. A comprehensive review of polyacrylamide polymer gels for
compliance control. Gasoline Explorer Dev 2015; 42:525-32.
11. Prashar A. shed tears for diagnosis. Springer Singapore; 2019.
12. Sarada K, Firoz S, Padmini K. In-situ gel systems: a review. Int J Curr Pharma Rev Res
2014; 15: 76-90.
13. Bhardwaj L, Sharma PK, Malviya R. A brief review of gastric-retaining formulations for
specific drug delivery. Special emphasis is placed on swimming in the lake gel system. Basic
Program Afr J Science 2011; 3:300–12.
14. Prabharan M, Mano JF. Chitosan-based particles as released drug delivery system. Drug
Delivery 2004; 12: 41-57.
15. Kaur P, Garg T, Rath G, Goyal AK. Dispensing nasal gel medicine: A novel approach to
targeting the brain through the mucosa membrane. Artificial cells Nanomed Biotéh 2016;
44:1167-76.
16. Browning TR, Heath RD. Acknowledging the calming effect Regarding the cost of
production and evidence of the F-22 program. J. Operations Management 2009; 27:23-44.
17. Dai T, Huang YY, K Sharma S, T Hashmi J, B Kurup D, R Hamblin. M. is a key microbe for
acute wound infections. The last one Anti-Infective Drug Discovery 2010; 5:124-51.
18. Figueira RB, Silva CJ, Pereira EV. Hybrid organic-inorganic sol- Gel coatings against metal
corrosion: a recent review growth J Symbol Technol Res 2015; 12:1-35.
19. Kumar A, Srivastava A, Galaev IY, Mattiasson B. Smart Polymers: physical forms and
bioengineering applications. Prog Polym Sci 2007; 32:1205-37.
20. Mishra M, Kumar P, Rajawat JS, Malik R, Sharma G, Modgil A. Nanotechnology: a
revolution in drug delivery science. Curr Pharm Dec 2018; 24:5086-107.
21. Langmaier F, Mockrejs P, Kolomaznik K, Mladek M. Biodegradable packaging material
from collagen hydrolyzate fixed protein. Waste Management 2008; 28:549-56.
22. HB N, Bakliwal SR, Pawar SP. Coming in-situ: a new trend controlled and sustained drug
delivery system. Inter J Pharm Tech Res 2010; 2:1398-408.
23. Jadhav UG, Dias RJ, Mali KK, Havaldar VD, more MI. Development of in situ gelling and
mucoadhesive fluids ondansetron prediction. Int J Chem Tech Res 2009; 1:953-61.
24. Packhaeuser CB, Schnieders J, Oster CG, Kissel T. In Formulation of parenteral drug
delivery systems: an overview. Eur J. Pharm Biopharm 2004; 58: 445-55.
25. Hatefi A, Amsden B. In situ biodegradable vaccine. drug delivery system. J Revision Release
2002; 80:9-28.
26. Lin Z, Gao W, Hu H, Ma K, He B, Dai W, et al. A new thermosensitive hydrogel system
with paclitaxel nanocrystals: top drug loading, sustained drug release, and local expansion
storage that ensures better efficacy and lower toxicity. J. Edited 2014; 174: 161-70.
27. Malik K, Singh I, Nagpal M, Arora S. Atrigel: potential parenteral drug control system.
Pharm Syn 2010; 1:74-81.
28. Jeong B, Kim SW, Baé YH. Thermosensitive left-gel opposite hydrogel. Adv Drug Delivery
Rev 2012; 64: 154-62.
29. Baldwin AD, Kiick KL. Synthetically modified polysaccharides polymer biomaterials. Pept
Sci: Biomolecular Res Original 2010; 94: 128-40.
30. Grassin Delile S, Buenestado A, Naline E, Faisy C, Blouquit Laye S, Couderc LJ et al.
intravenous drug delivery: effective and Noninvasive approach to systemic management: focus
opioids. Term Pharmacol 2012; 134:366-79.
31. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymer
nanoparticles as drug delivery equipment. J Edition Edition 2001; 70:1-20.
32. Jothi M, Harikumar SL, Aggarwal G. For in-situ ophthalmic gel. eye disease treatment. Inter
J Phar Pharm Sci Res 2012;3:1891.
33. Almeida H, Amaral MH, Lobao P, Lobo JM. In situ gelling systems: a strategy to improve
the bioavailability of ophthalmic pharmaceutical formulations. Drug Discover Today
2014;19:400-12. 34. Ruel Gariepy E, Leroux JC. In situ-forming hydrogels-review of
temperature-sensitive systems. Euro J Pharm Bio-Pharm 2004;58:409-26