• Home

• Info Zone
• Community
• Articles
• e-journal
• Contact
• Help
• My Page

Parte superior do formulário

partner-pub-6758 FORID:9 UTF-8 Search

Parte inferior do formulário

Home

Pharmaceutical Significance Of Chitosan

: A Review
By - 11/05/2006
in
• Latest Reviews
• Vol. 4 Issue 6
• 2006
• Login or register to post comments
• 5127 reads
Average:
0
Your rating: None

Sanjay S. Patel
The science of drug delivery is always affected by the choice of polymers
which act as carriers. Synthetic polymers frequently suffer from the
problem
of being non-biocompatible, non-biodegradable and expensive. Natural
polymers
therefore are a promising solution to this problem.
Among the natural polymer, Chitosan is the most abundant polysaccharide,
infact second only to cellulose. Chitosan is obtained by deacetylation of
chitin. The main commercial sources of chitin are the shell wastes of shrimp,
crab, lobster, krill, and squid. Chitosan is a natural, cationic, hydrophilic,
nontoxic, biocompatible and biodegradable polysaccharide suitable for application
in pharmaceutical technology. Being a bioadhesive polymer and having antibacterial
activity. The bioadhesive nature of chitosan can be attributed to the same
type of ionic interactions with mucosal membrane components. Chitosan is soluble
at acidic pH, forming gel; hydrogels are also formed in the presence of negative
charged drugs or polyanions and represent a sustained drug release form. The
aim of this review is to provide an insight into the many potential applications
of chitosan as a pharmaceutical excipient. Various investigations carried
out recently are reported, although references to research performed on chitosan
prior to the recent reviews have also been included where appropriate.
Introduction
There is growing interest in
developing chemical and biochemical processes to obtain and modify biopolymers,
and to other useful technical properties for their applications in different
fields.1-3 One of the latest and most interesting example is chitin,
it is mainly used for production of chitosan by a deacetylation reaction
usually obtained in alkaline medium. Chitosan exhibits several favorable properties,
such as biodegradability and biocompatibility.4 It also has
mucoadhesive properties due to its positive charges at neutral pH that enable
an ionic interaction with the negative charges of sialic acid residues of the
mucus.5,6 Some of which include binding, disintegrating, and tablet
coating properties. Numerous studies have demonstrated that chitosan and
its derivatives (N-trimethyl chitosan, mono-N-carboxymethyl chitosan) are
effective and safe absorption enhancers to improve mucosal (nasal, peroral)
delivery of hydrophilic macromolecules, such as peptides, proteins, and
heparins. Chitosan
has been developed for a variety of biomedical applications including wound
dressings and drug delivery systems. In the context of drug delivery, chitosan
has been used as a stabilizing constituent of liposomes7 as an
excipient controlling drug release in oral formulations.8 The polymer has
also been investigated as a potential adjuvant for swellable controlled drug
delivery systems. Chitosan exhibits a myriad of biological actions, namely
hypocholesterolemic, antimicrobial, and wound-healing properties. Low toxicity
coupled with wide applicability makes it a promising candidate not only for the
purpose of drug delivery for a host of drug moieties (anti-inflammatory,
peptides, etc) but also as a biologically active agent. Chitosan nano-and
micro-particles are also suitable for controlled drug release. Association of
vaccines to some of these particulate systems has shown to enhance the antigen
uptake by mucosal lymphoid tissues, thereby inducing strong systemic and
mucosal immune responses against the antigens.
Chemical Structure and Preparation of Chitosan
Chitin
and chitosan are one of the most abundant polysaccharide in nature, after
cellulose. Chitin is long and unbranched homopolymer,9 it form a
major part of cell wall of crustaceans (shrimp, crab, lobster, krill,
and squid), insects, fungi, annelids, molluscus and coelentrates. Structurally, it is poly
(N-acetyl-2-amino-2-deoxy-D-glycopyranose) in which the N-acetyl-2-amino-2-deoxy-
D-glycopyranose
units are linked by (1-4) β bonds.
Its β (1-4) linked glucose-NAC
units with a three dimensional α-helical configuration are stabilized by
hydrogen bonding.10 Chitin is highly hydrophobic material, insoluble
in eater as well as most organic solvents but its aqueous solubility can be
increased by deacetylation.11 The principal derivative of chitin,
namely chitosan [(1-4) 2-amino-2-deoxy-β-D-glucan] is a unique
polysaccharide and hydrophilic polymer, which is usually obtained by alkaline
deacetylation, the two polymers being distinguished by solubility in dilute
aqueous acid solutions.11,12 Commercial chitin and chitosan consists of both
types of monomers. Chitosan is found in nature, to a lesser extent than
chitin, in the cell walls of fungi. The
annual biosynthesis of chitin has been estimated to 109 to 1011 tons. Chitin is widely
distributed in
nature. Among several sources, the exoskeleton of crustaceans consists of 15%
to 20 % chitin of dry weight. Chitin found in nature is a renewable
bioresource. 13-16 Chitin and chitosan are both prepared
using the common process illustrated and described in Figure 1. The chemical
and biological properties of chitosan17 are listed in Table 1. The
pharmaceutical requirement for chitosan include appearance, particle size,
density, viscosity, loss on drying and heavy metal content are listed in Table
2.
Figure: - 1. Preparation of Chitin and Chitosan
Shellfish wastes from food processing (shrimp, crab, squid,
lobster,)

Decalcification in dil. Aqueous HCL solution

(3 % to 5 % HCL w/v at room temperature)

Deproteination in dil. Aqueous NaOH solution

(3% to 5 % w/v NaOH, 80° C to 900° C for a few hrs. or room temperature
overnight)
Decolarization in 0.5 % KmnO4 aqueous and oxalic acid aqueous or sunshine

Chitin

Deacetylation in hot concentration NaOH solution

(40 % to 50 % w/v NaOH, at 90° C to 120° C for 4 to 5 hrs.)

Chitosan

The crude chitosan is dissolved in aqueous 2 % w/v acetic acid.

Then the insoluble material is removed giving a clear supernatant solution,
which is neutralized with NaOH solution resulting in a purified sample of
chitosan as a white precipitate. Further purification may be necessary to
prepare medical and pharmaceutical-grade chitosan.
The crude chitosan is dissolved in aqueous 2 % w/v acetic
acid. Then the insoluble material is removed giving a clear supernatant
solution, which is neutralized with NaOH solution resulting in a purified
sample of chitosan as a white precipitate. Further purification may be necessary
to prepare medical and pharmaceutical-grade chitosan.
Table: - 1. Chemical and Biological Properties of Chitosan17
Chemical properties of chitosan Biological properties of chitosan
Cationic Biocompatibility
polyamine
High charge density at pHs < 6.5 Natural polymer
Adheres to negatively charged Safe and non-toxic
surfaces
Forms gels with polyanions Haemostatic
High molecular weight linear Biodegradable to normal body
polyelectrolyte constituents
Viscosity, high to low Bacteriostatic / Fungistatic
Chelates certain transitional metals Spermicidal
Amiable to chemical modification Anticancerogen
Reactive amino/hydroxyl groups Anticholestermic
Table-2. Specification of Pharmaceutical-Grade Chitosan17,18.
Parameters Description
Appearance White or
(powder or flake) yellow
Particle size < 30 µm
Viscosity a≤5
cps
Density between 1.35
to 1.40 g/cm3
Molecular 50,000 to
weight 2,00,000 Da.
PH 6.5 to 7.5
Moisture > 10 %
content
Ash value >2%
Mater ≤ 0.5 %
insoluble in water
Degree of 66 % to 99.8 %
deacetylation
Heavy metal < 10 ppm
(Pb)
Heavy metal < 10 ppm
(As)
Protein < 0.3 %
content
Loss on drying ≤ 10 %
Glass 203° C
transition temperature

Application of Chitosan in Pharmaceutical Formulation

Ophthalmic Drug Delivery
Chitosan exhibits favorable
biological behavior, such as bioadhesion, permeability-enhancing properties,
and interesting physico-chemical characteristics, which make it a unique
material for the design of ocular drug delivery vehicles.19 Due to
their elastic properties, chitosan hydrogels offer better acceptability, with respect
to solid or semisolid formulation, for ophthalmic delivery, such as suspensions
or ointments, ophthalmic chitosan gels improve adhesion to the mucin, which
coats the conjunctiva and the corneal surface of the eye, and increase
precorneal drug residence times, showing down drug elimination by the lachrymal
flow. In addition, its penetration
enhancement has more targeted effect and allows lower doses of the drugs.20
In contrast, chitosan based colloidal system were found to work as transmucosal
drug carriers, either facilitating the transport of drugs to the inner eye
(chitosan-coated colloidal system containing indomethacin) or their
accumulation into the corneal/conjunctival epithelia (chitosan nanoparticulate
containing cyclosporin). The microparticulate drug- carrier (micropsheres)
seems a promising means of topical administration of acyclovir to the eye.21
The duration of efficacy of the ofloxacin was increased by using high MW
(1930 kd) chitosan.22
Buccal and Sublingual Drug Delivery
Buccal drug delivery represents a
versatile application, not only in the treatment of local infections, such as periodontal
diseases, stomatitis but also as
a topical route for systemic delivery of therapeutic peptides, avoiding
first-pass metabolism, acidity, and protease activity encountered in the
gastrointestinal tract. In these cases, mucoadhesion developed by a chitosan
hydrogel appears to be suitable for prolonging the residence time of the
pharmaceutical form, and improving the therapeutic effect.23
Bilayered devices will ensure the release of the drug occurs in a
unidirectional way.24, 25
Chitosan has a good mucoadhesive
property so it is used in buccal drug delivery and also used as a absorption
enhancer. Buccal tablets based on chitosan micropsheres containing
chlorhexidine diacetate showed a prolonged release of the drug in the buccal
cavity. The loading of chlorhexidine into chitosan to improve the antimicrobial
activity of the drug.26 An additional antifungal effect was thought
to be achieved since chitosan also inhibits the adhesion of candida albicans
to human buccal cells.22 Bioadhesive tablets of nicotine
containing 0% to 50% w/w glycol chitosan give the acceptable adhesion.27
Directly compressible bioadhesive tablets of ketoprofen containing chitosan and
sodium alginate in
the weight ratio 1:4 showed sustained
release 3 hours after intraoral
(sublingual site of rabbits) drug administration. The buccal bilayered devices
(bilaminated film, bilayered tablets) using a mixture of drugs (nifedipine and
propranolol Hcl) and chitosan, with and without anionic cross-linking polymers
(polycarbophil, sodium alginate, gellan gum), demonstrated that these devices
show promising potential for used in controlled delivery of drugs to the oral
cavity.27 Drug-empty microparticles have an antimicrobial activity
due to the chitosan itself give antimicrobial activity.26
Periodontal Drug Delivery
Local delivery of drugs and other
bioactive agents directly into the poeriodontal pocket has received a lot of
attention lately. For example. for moderate to severe periodontal diseases,
antimicrobial agents are used to kill and or suppress the plaque bacteria.
However, systemic administration of these drugs has certain disadvantages such
as the necessity for frequent dosing to maintain the drug concentrations at the
therapeutic level in the plasma, poor patient compliance, super infections
caused by resistant organisms and gastrointestinal and systemic side-effects.28,
29
An ideal formulation should be easy to deliver, has good retention at
the target site, and provide sustained release of the drug. Muco/bioadhesive
polymers increase the residence time of the formulation in the oral cavity.
This will enhance drug penetration, localize the drug for local therapy, target
the diseased tissue, and improve efficacy and acceptability.30
Being a muco/bioadhesive polymer,
chitosan is considered a good candidate for oral cavity drug delivery.31,32
The antibacterial activity of chitosan could be due to the electrostatic
interactions between the amine groups of chitosan and the anionic sites on
bacterial cell wall because of the presence of carboxylic acid residues and
phospholipids.33 Chitosan is a biologically safe polymer and
prolongs the adhesion time of oral gels and drug release from them. Chitosan
also inhibits the adhesion of Candida albicans to human buccal cells and
has antifungal activity. Hydroxyapatite (HA) has been used as a bone substitute
in dental treatment for periodontal and endosteal implant repairs, implantation
of tooth extraction sockets to maintain alveolar ridges height and augmentation
of deficient alveolar ridges it improve denture support and stability.34,
35
but the major disadvantage of HA is that the particle can be leaked
through the incision or migrate to the surrounding soft tissues causing
inflammation.36-38 To overcome this problem, chitosan containing
quick-hardening paste was developed as a bone substitute. The use of this paste
will minimize the inflammation.39 Chitosan gel and chitosan film
containing chlorhexidine gluconate for local delivery were developed. A
monolayer and multilayered film of chitosan PLGA containing ipriflavone were
showed to prolong drug release for 20 days in vitro.40
Nasal Drug Delivery
The nasal mucosa presents an ideal site
for bioadhesive drug delivery systems.41 Bioavailability and residence time of the
drugs that are administered via the nasal route can be increased by bioadhesive
drug delivery systems. Chitosan drug delivery systems, such as microspheres,
liposomes, and gels, have been demonstrated to have good bioadhesive
characteristics and swell easily when in contact with the nasal mucosa. Various
chitosan salts (Chitosan lactate, chitosan aspartate, chitosan glutamate, and
chitosan hydrochloride) showed nasal sustained release of vincomycin
hydrochloride.42 Bioadhesive
chitosan microspheres of pentazocine for intranasal systemic delivery
significantly improved bioavailability with sustained and controlled blood
level profiles compared to intravenous, oral administration.44 Diphtheria
toxoid (DT) associated to chitosan microparticles results in protective
systemic and local immune response against DT, and enhances significant IgG
production after nasal administration.43
The nasal absorption of insulin after administration in chitosan
powder was the most effective formulation for nasal delivery of insulin in
sheep compared to Chitosan nanoparticles and chitosan solution. Different types
of nasal vaccine systems have been described to include cholera toxin,
microspheres, nanoparticles, liposomes, attenuated virus and cells, and outer
membrane proteins (proteosomes). Nasal formulations induced significant serum
IgG responses similar to and secretory IgA levels superior to what was induced
by a parenteral administration of the vaccine.45
Gastrointestinal (Floating) Drug Delivery
Floating systems have a density lower
than the density of the gastric juice. Thus, gastric residence time and hence
the bioavailability of drugs that are absorbed in the upper part of the GI
tract will be improved. Intragastric floating dosage forms are useful for the
administration of drugs that have a specific absorption site, area insoluble in
the intestinal fluid, or area used for the treatment of gastric diseases.
Chitosan granules having internal cavities were prepared by deacidification.
When added to acidic (pH 1.2) and neutral (deionized distilled water) media,
these granules were immediately buoyant and provided a controlled release of
the candidate drug prednisolone. Both chitosan granules and chitosan-laminated
preparations could be helpful in developing drug delivery systems that will
reduce the effect of gastrointestinal transit time. Floating hollow
microcapsules of melatonin produced have an interesting gastro retentive
controlled-release delivery system for drugs. Release of the drug from these
microcapsules was greatly retarded with release lasting for several hours (1.75
to 6.7 hours in simulated gastric fluid), depending on processing factors. Most
of the mucoadhesive microcapsules developed tended to retain in stomach for
more than 10 hours 46,47.( metoclopramide and glipizide loaded
chitosan micropsheres)
Peroral Drug Delivery
Chitosan is an excellent candidate for
the treatment of oral mucositis. Its bioadhesive and antimicrobial properties offer
the palliative effects of an occlusive dressing and the potential for
delivering drugs, including anticandidal agents.48 Nifedipine embedded
in a chitosan matrix in the form of beads showed prolonged-release of drug
compared to granules.49 The chitosan-coated nanospheres reduced
significantly the blood calcium level compared with uncoated nanospheres, and
the reduced calcium level was sustained for a period of 48 hours.50 A novel
mucoadhesive
DL-lactide/glycolide copolymer (PLGA) nanospheres system to improve peptide
absorption and prolong the physiological activity following oral administration
was prepared. Chitosan has a mucoadhesive properties and most of its
derivatives, a presystemic metabolism of peptides on the way between the dosage
form and the absorption membrane can be strongly reduced. Based on these unique
features, the coadministration of chitosan and its derivatives leads to a
strongly improved bioavailability of many perorally given peptide drugs, such
as insulin, calcitonin, and buserelin.51
Intestinal Drug Delivery
Sustained intestinal delivery of drugs,
such as 5-fluorouracil (choice for colon Carcinomas) and insulin (for diabetes
mellitus) seems to be a feasible alternative to injection therapy.52 A formulation
was developed that could bypass the acidity of the stomach and release the
loaded drug for long periods into the intestine by using the bioadhesiveness of
polyacrylic acid, alginate, and chitosan. Bromothymol blue was taken as a model
drug. The formulation exhibited bioadhesive property and released the drug for
an 80-day period in vitro. Chitosan/calcium alginate microcapsules
containing nitrofurantoin (NF) showed sustained release of drug. Drug release
into the gastric medium is found to be relatively slow compared to that into
the intestinal medium.53
Colon Drug Delivery
Chitosan was used in oral drug
formulations to provide sustained release of drugs. Recently, it was found that
chitosan is degraded by the microflora that are available in the colon. As a
result, this compound could be promising for colon-specific drug delivery.
Chitosan esters, such as Chitosan succinate and Chitosan phthalate have been
used successfully as potential matrices for the colon-specific oral delivery of
diclofenac sodium.54 Recently the same researchers also developed an
iron-cross-linked derivative of hydroxamated Chitosan succinate, as a matrix
for oral theophylline beads.55 Systems for colon delivery containing
paracetamol, mesalazine, and insulin have been studied and give satisfactory
results.56-59
Transdermal Drug Delivery
Chitosan has good film-forming
properties. The drug release from the devices are depends on the membrane
thickness and cross-linking of the film.60 Chitosan-alginate
poly electrolyte complex (PEC) has been prepared in situ in beads and
microspheres for potential applications in packaging, controlled release
systems, and wound dressings.61 Chitosan gel was used as the drug
reservoir. The drug-release profiles showed that drug delivery is completely
controlled by the devices. The rate of drug release was found to be dependent
on the type of membrane used.62 A combination of Chitosan membrane and
Chitosan hydrogel containing lidocaine Hcl, a local anesthetic, is a good
transparent system for controlled drug delivery and release kinetics.63
Chitosan
gel beads containing the anti-inflammatory drug prednisolone showed sustained
release of drug with reduced inflammation indexes that resulted in improved
therapeutic efficacy.64
Vaginal Drug Delivery
Chitosan vaginal tablet containing
metronidazole, acriflavine, and other excipients give adequate release and good
adhesion properties.65,66 Chitosan, modified by the introduction of
thioglycolic acid to the primary amino groups of the polymer, embeds
clotrimazole, an imidazole derivative widely used for the treatment of mycotic
infections of the genitourinary tract. By introducing thiol groups, the
mucoadhesive properties of the polymer were strongly improved, and this
resulted in an increased residence time of the vaginal mucosa tissue (26 times
longer than the corresponding unmodified polymer), guaranteeing a controller
drug release in the treatment of mycotic infections.67
Gene Delivery
The course of many hereditary
diseases could be reversed by gene delivery. In addition, many acquired diseases
such as multigenetic disorders and those diseases caused by viral genes could
be treated by genetic therapy.68 Gene delivery systems include viral
vectors, cationic liposomes, polycation complexes, and microencapsulated
systems.69,70 Viral vectors are advantageous for gene delivery
because they are highly efficient and have a wide range of cell targets.
However, when used in vivo they cause immune responses and oncogenic effects.
To overcome the limitations of viral vectors, non-viral delivery systems are
considered for gene therapy. Non-viral delivery system has advantages such as
ease of preparation, cell/tissue targeting, low immune response, unrestricted
plasmid size, and large-scale reproducible production.71 Chitosan
has been used as a carrier of DNA for gene delivery applications. Also,
Chitosan could be a useful oral gene carrier because of its adhesive and
transport properties in the GI tract. MacLaughlin et al.72 Showed
that plasmid DNA containing cytomegalo virus promoter sequence and a luciferase
reporter gene could be delivered in vivo by Chitosan and depolymerized Chitosan
oligomers to express a luciferase gene in the intestinal tract.
Vaccine Delivery
Bovine serum albumin and diphtheria
toxoid loaded Chitosan microspheres give good tissue compatibility with a
long-lasting drug delivery system in wistar rats for several days.73
Diphtheria toxoid associated to chitosan microparticles results in protective
systemic and local immune response against diphtheria toxoid after oral
vaccination, and in significant enhancement of IgG production after nasal
administration.74 Various Chitosan-antigen nasal vaccines have been
prepared. These include cholera toxin, diphtheria toxoids, liposomes,
nanoparticles, attenuated virus and cells, and proteosomes (outer membrane
proteins). They induced significant serum IgG responses similar to and
secretory IgA levels superior to what was induced by a parenteral
administration of the vaccine.45
Miscellaneous Applications
Amiji et al.75 modified
chitosan membranes surface by complexation and interpenetration of anionic
polysaccharides,
heparin and dextran sulfate for improved blood compatibility in haemodialysis.
The permeability of urea and creatinine did not change significantly upon
modification with heparin and dextran sulfate. However it did decrease the
permeability coefficients of glucose, vitamin B2 and Vitamin B12. In addition
the modifications significantly shorten the plasma recalcification time leading
to fibrin clot formation. The study showed that the modified membranes resist
complement activation and platelet adhesion and activation.
Jing et al.76 have investigated
the effect of chitosan in patients with chronic renal failure undergoing long
term stable haemodialysis treatment. Ingestion of chitosan effectively reduced
serum cholesterol level and increased serum hemoglobin levels. Significant reduction
in urea and creatinine levels in serum was observed after 4 weeks of chitosan
ingestion. The data suggests that chitosan might be effective treatment for
oral renal failure patients.
N-Carboxybutyl chitosan was studied
in wound healing in rabbits; where complete re-epithelialization was observed
with all the epithelial layers represented on 30th day of treatment.
N-Carboxybutyl chitosan thus presented an interesting role in tissue
reconstruction.77 Chitosan has also been used to prepare bandages
for wound healing.78 Malette
et al.79 showed that treating
various dog tissues with chitosan solution resulted in the inhibition of
fibroplasia with enhanced tissue regeneration. For veterinary wound healing
significant progress has been made and the company sunfive Inc. (Japan)
has now developed and marketed a chitosan cotton (Chitopak TMC) and chitosan
suspension (Chitofine TMS). The 3M company in UK
has marketed TegasorbTM a wound healing product containing
chitosan.
Malette et al.80 have shown
that chitosan solution formed a coagulum in contact with whole blood, where the
possible mechanism appeared to be a reaction between red cell membrane and the
chitosan solution leading to cross linkage or repolymerization. In further
experiments they have found that such homeostatic coagulum formed withstands
arterial pressure in vascular grafts and leads to the growth of vascularised
smooth muscle vessel wall with an andothelial intima. In addition they have
drawn the conclusion from the experiment that the chitosan solution used to
treat various tissues results in the inhibition of fibroplasia and the
regeneration of normal tissue elements.
Fradel et al.81 have demonstrated
that chitosan is an effective and adequate homeostatic agent even under the
most severe conditions of anticoagulation. However their observations regarding
role of chitosan in graft healing process seem to support Mackenzie’s82 hypotheses of
graft
healing and pseudo intimal formation. The initial event of healing involves
platelet and fibrin aggregates followed by red blood, white blood cells and
finally by monocytes that differentiate into fibroblasts, then myofibroblasts
and finally pseudo endothelial cells. From the observations their final
conclusion is that chitosan is a good substitute for blood for graft
homeostasis.
Muzzarelli et al.83 have attempted to prepare N-Carboxymethyl chitosan
which then was submitted to sulfation. In this study they have shown that
N-Carboxymethyl chitosan (NCMC) sulfates are blood anticoagulants, the best of
them being N-Carboxymethyl chitosan 3,6 disulfate of low molecular weight. The
said compound exhibited the same blood anticoagulant activity as heparin and showed
no adverse effects on the cellular structures when added to blood to be used in
vitro.
An interesting application of
carboxymethyl chitin was reported in the preparation of artificial red blood
cells.84 A o/w type emulsion obtained from sheep hemolysate and
lecithin in dichloromethane was dispersed in an aqueous carboxymethyl chitin
solution to form a w/o/w type emulsion. Removal of the organic solvent results
in an aqueous suspension of artificial red blood cells.
Glucosamine (Chitosamine) found in
chitin, mucoproteins and muco-polysaccharides is isolated from chitin or
prepared synthetically. Glucosamine sulphate or hydriodide has been given in
treatment of rheumatic disorders including osteoarthriris.85 Water
insoluble membranes can be prepared fron cationic chitosan and anionic algin
polysaccharides, which are quite useful for encapsulation of cells e.g. those
of Pancrease (insulin producing) for implantation. Thus it offers a very good
material for artificial organ production.86
Summary
Chitosan is the most abundant polysaccharide, infact second only cellulose, it is
obtained by alkaline
N-deacetylation of chitin. Chitosan has been widely investigated as a drug
carrier for many possible routes of administration because of chitosan has
favorable biological properties, such as non-toxicity, biocompatibility,
biodegradability, and antibacterial characteristics. The physical and chemical
properties of Chitosan, such as inter- and intramolecular hydrogen bonding and
the cationic charge in acidic medium, makes this polymer more attractive for
the development of conventional and novel pharmaceutical product. Chitosan can
serve a number of purpose, including as a coating agent, gel former,
controlled-release matrix, in addition to including desirable properties, such
as mucoadhesion and permeation enhancement to improve oral bioavailability of
drug. The microbial floras that are present in the colon degrade Chitosan; as a
result Chitosan is a good candidate for site-specific drug delivery. Chitosan
has been found to be of use many clinical situations for ameliorating variety
of human ailments, ranging from wound healing glomerulonephritis up to
substitute of artificial red blood cells. These multiform aspects of chitosan
parallel to those as a drug carrier make it a unique polymer in pharmaceutical
field. Additional safety and toxicology studies in accordance with the FDA’s
guidelines for new excipient development would however be desire to further
promote the use of this polymer as a pharmaceutical excipient.
References
1. Skaugrud, O, Drug Cosmetic Ind., 1991;148:24-29.
2. IIIum, L, Pharm. Res., 1998;15:1326-1331.
3. Akbuga, J, Int. J. Pharm. Adv., 1995;1:1-18.
4. Muzzarelli RAA, Baldassare V, Conti F, Gazzanelli G, Vasi V, Ferrara P,
Biangini G. Biomaterial, 1988;8:247-252.
5. Lehr CM, Bouwstra JA, Schacht EH, Junginger HE, Int. J. Pharm, 1992;78:43-48.
6. Felt O, Furrer P, Mayer JM, Plazonnet B, Buri P, Gurny R. Int. J. Pharm.,
1999; 180:185-193
7. Henriksen, I, Sminstad, G, and Karslen, J, Int. J. Pharm., 1994;101:227-236.
8. Imai, T, Shiraishi, S, Saito H, and Otagiri, M, Int. J. Pharm., 1991;67:11-20.
9. Chandy T, and Sharma CP, Biomat, Art cells, Art Org., 1990;18:1-24.
10. Kas HS, J. Microencapsulation, 1997;14:689-711.
11. Kristmundsdottir T, Ingvarsdottir K, and Saemundsdottir G, Drug Dev. Ind.
Pharm., 1995;21:1591-8.
12. Roberts GAF, In: Chitin Chemistry edited by G.A.F. Roberts, Macmillan
Press, Haundmills; 1992:274.
13. Roberts GAF, Structure of chitin and chitosan, In: Roberts GAF, ed. Chitin
Chemistry, Macmillan, Houndmills. 1992:1-53
14. Kurita K, Chemical modification of chitin and Chitosan, In: Muzzarelli
RAA, Jeuniaux C, Gooday GW, eds, Chitin in Nature and Technology, Plenum:
New York, NY. 1986:287-293.
15. Rha CK, Rodriguez-Sanchez D, Kienzle-Sterzer C, Novel application of chitosan.
In: Coiwell RR, Pariser ER, Sinskey AJ, eds. Biotechnology of Marine Polysaccharides.
Hemisphere: Washington, DC. 1984:284-311.
16. Struszezyk H, Warwro D, Niekraszewiez A, Biodegradability of chitosan
fibres. In: Brine CJ, Sandford PA, Zikakis JP, eds. Advances in chitin and
chitosan, Elsevier Applied in Chitin and Chitosan, Elsevier Applied Science:
London, UK. 1991:580-585.
17. Sanford PA, Chitosan: Commercial uses and potential applications. In:
Skjak G, Anthonsen T, Sanford P, eds. Chitin and Chitosan - sources, Chemistry,
Biochemistry, Physical Properties and Applications, Elsevier: London, UK,1989:51-69.
18. Sakurai K, Maegawa T, Takahashi T, polymer, 2000;41:7051-7056.
19. Lonso MJ, Sanchez A, J. Pharm. Pharmacol., 2003;55:1451-1463.
20. Kaur, I, and Smitha, R, Drug Dev. Ind. pharm., 2002;28:353-369.
21. Genta I, Conti B, Perugini P, Pavanetto F, Spadaro A, Puglisi G, J. Pharm.
Pharmacol., 1997;49:737-742.
22. K. Muthusamy, TK. Ravi, G. Govindharajan, S. Gopalakrishnan, Ind. Journal
of Pharm. Edu., 2004;38:138-140.
23. Needleman IG, and Smales, FC, Biomaterials, 1995;16:617-624.
24. Nagai T, Machida Y, Adv. Drug Deliv. Rev., 1993;11:179-191.
25. Anders R, Merkle HP, Int. J. Pharm., 1989;49:231-240.
26. Giunchedi, p., et al, Eur. J. Pharm. Biopharm., 2002;53:233-239.
27. Miyazaki S, Nakayama A, Oda M, Takada M, Attwood D, Biol. Pharm. Bull.,
1994; 17:745-747.
28. Genco RJ. J. periodontal., 1981;52:545-558.
29. Golomb G, Friedman M, Soskoline A, Stabholz A, Sela MN, J. dent. res.,
1984;63:1149-1153.
30. Robinson JR, Rationale of bioadhesion /mucoadhesion, In: Gurny R, Junginger
HE, eds. Bioadhesion: Possibilities and future Trends. Wissenschaftliche:
Stuttgart, Germany. 1990; 13-15.
31. Needleman IG, Martin GP, Smales FC, J Clin. Periodontal. 1998; 25:74-82.
32. Senel S, Kremer MJ, Kas S, Wertz PW, Hincal AA, Squier CA. Biomaterials.
2000; 21:2067-2071.
33. Seo H, shoji A, Isoh Y, Kawamura M, Sakagami Y, Antibacterial fiber blended
with chitosan. In:Karnicki ZS, Brzeski MM, Bykowski PJ, Wojtasz-Pajak A, eds.
Chitin world Wirtschaftverlag, Germany. 1994;623-631.
34. A. Oglivie, RM. Frank, EP. Benque, M. Gineste, M. Heughebaert, J. Hemmerle,
J. Periodontal Res. 1987;22:270-283.
35. HW. Denissen, K. de Groot, J. Prosthet. Dent. 1979; 42:551-556.
36. JN. Kent, JH. Quinn, MF. Zide, IM. Finger, M. Jarcho, SS. Rothstein, J.
Am. Dent. Assoc. 1982;105:993-1001.
37. HD. Larsen, IM. Finger, IR. Guerra, JN. Kent, J. Prosthet. Dent., 1983;49:461-470.
38. Y. Takagi, Nihon Shika Hyoron. 1988;543:57-68.
39. Radi Hejazi, Mansoor Amiji, J. of Controlled Release, 2003:89:151-165.
40. Perugini P, Genta I, Conti B, Modena T, Pavanetto F. Int. J. Pharm. 2003;252:1-
9,38.
41. Turker S, Onur E, Ozer Y,. Pharm World Sci. 2004;26:137-142.
42. Cerehiara T, Luppi B, Bigueei F, Zeeehi V, J Pharm Pharmacol. 2003;55;1623-
1627.
43. Vander Lubben IM, Kersten G, Fretz MM, Beavery C, Coos Verthoef J, Janginger
HE, Vaccine. 2003;28:1400-1408.
44. Sankar C, Rani M, Srivastava AK, Mishra B, Pharmazie. 2001;56:223-226
45. IIlum L, Jabbal-Gill I, Hinchcliffe M, Fisher AN, Davis SS, Adv Drug Deli
Rev. 2001;23; 51(1-3):81-96.
46. JK. Patel, MS. Bodar, AF. Amin, MM. Patel, Indian J. Pharm. Sci., 2004;66:300-
305.
47. Jayvadan Patel, Praful Bharadia, Avani Amin, Madhabhai Ptael, Drug Del.
Tech., 2004; 4:48-53.
48. Aksungur P, Sungur A, Unal S, skit AB, Squier CA, Enel S . J. Controlled
Release., 2004; 98:269-279.
49. Chandy T, Sharma CP. Biomaterials, 1992;13:949-952.
50. Kawashima Y, Yamamoto H, Takeuchi H, Kuno Y. Pharm Dev Technol.,
2000;5:77-
85.
51. Bernkop-Schnurch A. Int. J. Pharm., 2000; 20:1-13.
52. Ramdas M, Dileep KJ, Anitha Y, Paul W, Sharma CP. J. Biomater Appl., 1999;
13:290-206.
53. Hari PR, Chandy T, Sharma CP. J. Microencapsul., 1996;13:319-329.
54. Aiedeh K, Taha MO, Arch. Pharm, Weinheim, 1999;332:103-107.
55. Aiedeh K, Taha M.O, Eur. J. Pharm. Sci., 2001;13:159-168.
56. Sinha, VR, Kumria R. Int. J. Pharm., 2002;249:23-31.
57. Tozaki H, et al. J Controlled Release, 2002;82:51-61.
58. Tozaki H. J. Pharm. Sci., 1997;86:1016-1021.
59. Zhang H, Alsarra IA, Neau SH. Int. J. Pharm., 2002;239:197- 205.
60. Thacharodi D, Rao KP, Biomaterials, 1995;16:145-148.
61. Yan X, Khor E, Lim LY. Chem. Pharm. Bull. (Tokyo), 2000;48:941-946.
62. Thacharodi D, Rao KP, Biomaterials, 1995;16:145-148.
63. Thein-Han WW, Stevens WF. Drug Dev. Ind. Pharm., 2004;30:397-404.
64. Kofuji K, Akamine H, Qian CJ, Watanabe K, Togan Y, Nishimura M, Sugiyama
I, Murata Y, Kawashima S. Int. J. Pharm., 2004;19:65-78.
65. El-Kamel A, Sokar M, Naggar V, Gamal SA, AAPS PharmSci.Tech., 2002; 4:44.
66. Gavini E, Sanna V, Juliano C, Bonferoni MC, Giunchedi P. AAPS Pharm Sci
Tech., 2002; 3:E20.
67. Kast CE. J. Controlled Release, 2002;81:354-374.
68. RC. Mulligan, Science.1993;260:926-932
69. PL. Chang, N. Shen, AJ. Westcott , Hum. Gene Ther., 1993;4:433-440.
70. KY. Lee, IC. Kwon, YH. Kim, WH. Jo, SY. Jeong, J. Controlled Release,
1998;51:213-220.
71. KW. Leong, HQ. Mao, VL. Truong-Le, K. Roy, SM. Walsh, J. T. J. Controlled
Release. 1998;53:183-193.
72. FC. MacLughlin. RJ. Mumper, J. Wang, J. M. Tagliaferri, I. Gill, M. Hinchcliffe,
AP. Rollad, J. Controlled Release, 1998;56:259-272.
73. Jameela S R, Misra A, Jayakrishnan A. J. Biomater. Sci. Polym. Ed., 1994;6:621-
632.
74. Van der Lubben IM, Kersten G, Fretz MM, Beuvery C, Coos Verhoef J, Junginger
HE. Vaccine. 2003; 28:1400-1408.
75. Amiji MM, J. Biomat. Sci. Polym. Ed., 8(4);1996:281-298.
76. Jing SB,….et al., J. Pharm. Pharmacol., 49(7);1997:721-723.
77. Muzzarelli RAA. and Biagini M., J. Biomat. Compat. Polym., 5(4);1990:396-411.
78. Takagi….et al., JP 02268766 A, 1990 11 Heisei Japan.
79. Malette WG, Quigley J. and Adickes E.D., Plenum press, 1986.
80. Malette WG., ….et. al., Ann. Tho. Sirg., 36;1983:55.
81. Fradet G…..et al., Chitin in nature and technology, Muzzarelli R.
Jeunix, Gooday Eds., New York: Plenum, 1986:443-451.
82. Mackenzie JR., Arch. Surg., 97;1968:879.
83. Muzzarelli RAA, Chitin in nature and technology, Muzzarelli R., Jenuiaux,
Gooday Eds., New York: Plenum, 1986.
84. Kato A. Arakawa M. and Kondo T., J. Microencapsulation, 1;1984:105.
85. Reynolds, James EF. ed., Martindale’s the extra pharmacopoeia, 1993:1374.
86. Mathur NK. and Mathur, Vandana, Chemical Weekly, 10;1999:163-164.
About Authors
Sanjay S. Patel1, Natavarlal M. Patel1,
Girish N. Patel2, Kanu R. Patel1
1. Shri B. M. Shah College of Pharmaceutical Education and Research, Modasa
2. Shri S.
K. Patel College
of Pharmaceutical Education and Research, Kherva
Correspondence Address

Sanjay S. Patel (M. Pharm)

Mr. Sanjay S. Patel earned his M. Pharm. in Pharmaceutical Technology from
S. K. Patel college of Pharmaceutical Education and Research, Ganpat University,
Kherva, Gujarat, India. Presently he is working as a lecturer in the department
of Pharmaceutics and Pharmaceutical Technology at Shri B. M. Patel College
of Pharmaceutical Education and Research, Modasa, Gujarat, India. He is also
working towards his PhD.
Office-912774249587, Fax- 912774249482, E-MAIL:-onlysanju2004@yahoo.co.in

Natavarlal M. Patel
Principal in Shri B. M. Shah College of Pharmaceutical Education and Research,
Modasa, Gujarat, India
Girish N. Patel
Lecturer in pharmaceutical technology department, S. K. Patel College of
Pharmaceutical Education and Research,
Ganpat University, Kherva, Gujarat

Kanu R. Patel
Lecturer in pharmaceutical technology department, Shri B. M. Shah College
of Pharmaceutical Education and Research,
Modasa-383315, Gujarat
Quick Links
 Blogs
 Pharmacy Colleges
 Online Presentations
 PharmaTV
 Contests (PharmaGlow)
 GPAT
 Ask a Question
What's New ?
Free Webinar
Cleaning Validation
Free Download
Audio lectures on Statistics and ANOVA

Copyright © 2005 - 2011 Pharmainfo.net.