Chitosan-Based Micro and Nanoparticles: A Promising System for Drug Delivery

 

Lanka Divya*, M. Bhagavan Raju, Sushil Y Raut

Gland Institute of Pharmaceutical Sciences, Kothapet, Medak, Telangana.

 

ABSTRACT:

Chitosan (CS) as a natural polymer has been fabulated into a number of formulations such as films, hydrogels and particles based on its excellent properties such as biodegradable, biocompatible, bioadhesive, permeation-enhancement, antibiotic, antitumor properties etc., apart from those properties chitosan microparticles (CSMP) found a lot of applications in pharmaceutics such as vaccine delivery, mucosal delivery and gene delivery, etc. Down to the nanoscale, chitosan nanoparticles (CSNP) have more attractive properties more than that of CSMP, which further widen the applications of chitosan particles in biomedicine and biopharmaceutics. Considerable research efforts have been directed towards developing of safe and efficient chitosan-based particulate drug delivery systems. The present review aims at providing a major outline related to new findings on the pharmaceutical applications of chitosan-based micro/nanoparticulate drug delivery systems published over the past decade. CSNP have gained more attention as drug delivery carriers because of their better stability, low toxicity, simple and mild preparation method and providing versatile routes of administration. Their sub-micron size not only suitable for parenteral application, but also applicable for mucosal routes of administration, i.e., oral, nasal, and ocular mucosa, which are non-invasive routes, drug loading, release characteristics and applications are covered in this review. This review emphasizes recent research on methods of CS preparation, applications and different aspects of chitosan based micro and nanoparticles in drug delivery.

 

 

1. INTRODUCTION:

Chitosan is a polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine and can be derived by the partial deacetylation of chitin. It is a biodegradable, biocompatible and hydrophilic polymer of low toxicity. It is a material found in abundance in shells of crustacean such as lobsters, prawns and crabs. It is insoluble under alkaline and neutral conditions, but can react with inorganic and organic acids such as hydrochloric acid, lactic acid, acetic acid and glutamic acid under acidic conditions. It has OH and NH2 groups that give rise to hydrogen bonding and these groups could act as nucleophilic agent to initiate the polymerization of methylmethacrylate leading to an irreversible attachment between chitosan and methylmethacrylate through different multipoint linkages. The cationic polyelectrolytic nature of chitosan could interact with a negatively charged mucosal surface.

 

It was also confirmed that coating liposomes with chitosan improved their adsorption to mucosal surfaces. Drug delivery formulations have gained huge support from emerging nanotechnology. Nanotechnology, which is still not a mature technology and thus, more appropriately called nanoscience, usually refers to research at the scale of 100 nm or less [1]. Nanotechnology has been evolving tremendously in last few decades and made enormous impact on many other research scopes. In the human health field, the introducing of nanotechnology gave rise to a novel concept ‘nanomedicine’. In definition, nanomedicine is the process of diagnosing, treating, and preventing disease and traumatic injury, relieving pain, and preserving and improving human health, using molecular tools and molecular knowledge of the human body [2]. Numerous nanomedicine research activities have been dedicated to drug delivery study. Many of the current ‘nano’ drug delivery systems which are remnants of conventional drug delivery systems that happen to be in the nanometer range, such as liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals.

 

Fig 1 Chemical synthesis of soluble chitosan from chitin

 

Due to the advantages of nanoscale size, these nanovehicles are capable of overcome tissue barriers in human body, reach specific disease sites and remain there longer to realize larger bioavailability. Some of them are even able to deliver loaded package to specific organelles. Even so, this research field develops so fast that all above mentioned nanocarriers are already called as ‘first generation’ nanomedicine. Conjugated with special target ligands, such as antibodies, peptides or other adaptors, these nanocarriers are able to target specific cell subsets. Functionalized with various functional groups, some of them become multifunctional nanocarriers, for instance, both capable of imaging and treating, both thermal and pH responsible, and so on. In addition, various nanocarriers such as organic and inorganic nanoparticles are combined to exert multiple functions. All of these refined mono or multiple nanocarriers could be termed as the second generation nano medicines or even are further subdivided to be ranked as more advanced generation. In current review, the preparation methods and biomedical applications of CSMP and CSNPs have been studied.

 

Crustacean Shells

Crustacean Shells

 

       

 

                              Demineralization

                                                 

 

                                 Deproteinization                                                               Deproteinization

 

 

 

 

 

 

                Hydrolysis                                            Deacetylation                                        Carboxymethylation

 

Oligosaccharide

Glucosamine

Carboxymethyl chitin

                                                                      

 

 

 

 

          Hydrolysis                                                  Acid solution                                                       Succinylation

Chitosan salts Soluble in water solution with pH 6

Chitosan succinamide solution with 7 to 12 pH

                                                         

	Oligosaccharide

 

 

 

Fig 2. Schematic Representation of Preparation of Chitosan from chitin

1.1 Chitosan and its Derivatives:

While chitosan provides a number of excellent properties, further derivatization of the amine functionalities can be carried out to obtain polymers with a range of properties.

 

A number of approaches, both chemical and enzymatic, have been tried to exploit the reactivity of the amine functional groups [3].

 

A) N-Trimethylene Chloride Chitosan (TMC):

A number of studies demonstrated that the charge on chitosan has a role in providing intestinal permeability. Hence, a quaternary derivatized chitosan (N-trimethylene chloride chitosan) was shown to demonstrate higher intestinal permeability than chitosan alone. The TMC derivative was used as a permeation enhancer for large molecules, such as octreotide, a cyclic peptide. Hamman and coworkers showed that the degree of quaternization of TMC influences its drug absorption-enhancing properties. ⁸Polymers with higher degrees of quaternization (> 22%) were able to reduce the transepithelial electrical resistance and thereby epithelial transport (in vitro) in a neutral environment (pH 7.4). The maximum reduction in transepithelial resistance was reached with TMC with a degree of quaternization of 48%. This degree of quaternization was also seen to be optimum for in vitro transport of model drugs across a Caco-2 monolayer [4].

 

B) Chitosan Esters:

Chitosan esters, such as chitosan succinate and chitosan phthalate have been used successfully as potential matrices for the colon-specific oral delivery of sodium diclofenac [5].  By converting the polymer from an amine to a succinate form, the solubility profile is changed significantly. The modified polymers were insoluble under acidic conditions and provided sustained release of the encapsulated agent under basic conditions. The same researchers also synthesized an iron cross-linked derivative of hydroxamated chitosan succinate, as a matrix for oral theophylline beads [6]. A similar colon-targeting application was suggested for this polymer.

 

C) Chitosan Conjugates:

Reactivity of the amine functionality can be exploited to covalently conjugate functional excipients to the polymer backbone. For example, Guggi and Bernkop attached an enzyme inhibitor to chitosan. The resulting polymer retained the mucoadhesivity of chitosan and further prevented drug degradation by inhibiting enzymes, such as trypsin and chymotrypsin [7]. This conjugated chitosan demonstrated promise for delivery of sensitive peptide drugs, such as calcitonin.

 

Chitosan structure and physicochemical Properties: 

Chitosan is a linear copolymer composed of Nacetyl-d-glucosamine and d-glucosamine units available in different proposion depending upon the degree of deacetylation. The history of chitosan dates back to the 19th century, when Rouget discussed the deacetylated form of chitin in 1859 [8]. It is obtained by the deacetylation of chitin which is an abundant natural source widely found in the shells in insects, crustaceans and several fungi. Chitin is insoluble in aqueous solution or organic solvents. However, chitosan can be dissolved in weekly acetic aqueous solution due to the protonation of amino groups. After refinement, chitosan has a rigid crystalline structure through inter- and intra-molecular hydrogen bonding. The primary amino groups offer chitosan some special properties such as water-solubility, hemocompatibility, and cationic groups which could react with a big number of anions or other negatively charged molecules. And also based on the cationic property, chitosan-based or coated formulations could adhere to negatively charged biosurfaces or membranes. The hydroxyl groups could serve as the modification sites by other molecules or polymers, by which a verity of chitosan derivatives have been developed [9].

 

Fig. 2.1 Chemical Structures of Chitin and Chitosan.

 

1.2.2 Biodegradability, Biological Properties and Toxicity of Chitosan:

Chitosan could be degraded by acid catalyzed degradation, for instance, in stomach. In addition, enzymes such as lysozyme, bacterial enzymes in the colon [10] and some chitosanases [11] can degrade chitosan by hydrolyzing the glucosamine–glucosamine, glucosamine–Nacetyl-glucosamine and N-acetyl-glucosamine–N-acetylglucosamine linkages in vertebrates [12]. Some studies revealed that the biodegradability of chitosan is deacetylation degree-dependent and the higher the deacetylation degree, the less the degradation is [13, 14]. Chitosan has some favorable biological properties including mucoadhesion, enhanced mucosal epithelial permeability, and immune adjuvant effects [15]. The mucoadhesive property of chitosan enhances or prolongs drug absorption and thus permits maximal drug availability to the mucosal epithelium. Smith et al. proposed that chitosan could enhance the epithelial permeability by transiently opening the cell tight junction [16]. While, chitosan as an immune adjuvant have been found to enhance local and systemic immune responses to influenza, tetanus toxoid, diphtheria and pertussis vaccines when delivered intranasally [17-20]. In addition, chitosan was found to be toxic for some bacteria [21]; therefore, it can serve as an antibiotic material.

1.2 MICROPARTICLES:

Microparticle, also called as ‘microsphere’ or ‘microcapsule’ have many applications in medicine. In most cases, microparticles are used as drug carriers to deliver drug to the areas of interest and slowly release encapsulated drug over a desired period of time to maintain an effective local drug concentration. Microparticles also has novel application in the foods, medical devices, chemical coatings, personal health testing kits, sensors for security systems, biochemical sensors water purification units for manned space craft, and high throughput screening techniques [22].

Chitosan particles have found a verity of applications in biomedical and pharmaceutical fields in past few decades. The Preparation Methods of Chitosan Microparticles also called microspheres were used to extend the life span of active drugs and control the drug release. The total dose and release kinetics can be manipulated to achieve desired result by varying the copolymer ratio, molecular weight, polymer concentration etc. First, the preparation methods of chitosan microparticles are discussed in this section. Fig. 2 represents these methods [23].

 

 

1.3 Chitosan Microparticles/nanoparticles

 

(A)                                                                                                         (B)

 

                                   (C)                                                                             (D)

Fig 3 (A) and (B) Chitosan microparticles, (C) and (D) Chitosan nano particles

 

Fig. 4 Methods for the Preparation of Chitosan Microparticles. (V.R. Sinha et al.2004, International Journal of Pharmaceutics)

1.4 Preparation methods of Chitosan Microparticles:

a) Ionotropic Gelation

The polycationic chitosan in weak acetic solution could be gelated by a verity of counterions including low molecular weight anions such as diphosphoric acid, tripolyphosphate, etc., hydrophobic17 counterions such as alginate, κ-carragenan, poly-1-hydroxy-1-sulphonate-propene-2, polyaldehydro-carbonic acid, high molecular weight ions such as octyl sulphate, lauryl sulphate, hexadecyl sulphate, and cetylstearyl sulphate [24]. Chitosan solution was extruded dropwise through a needle into various counterions aqueous solutions under magnetic stirring.

 

b) Emulsification and Ionotropic Gelation

In this method, water-in-oil (w/o) emulsion is obtained firstly by emulsifying chitosan aqueous solution in an oil phase containing proper surfactant. Thereafter, various counterions solutions are added to solidify chitosan emulsion droplets[25]. The particle size could be manipulated by controlling the size of chitosan emulsion droplets, which can be realized by using different emulsification means, i.e. magnetic stirring, homogenization or sonication. In addition, the quantity and concentration of cross-linking agents influence the final particle size as well. This method may have disadvantages of the use of organic solvent and harsh mechanical shear force.

 

 

c) Coacervation/ Precipitation

Since chitosan is insoluble in alkaline medium, chitosan microparticles can form when chitosan solution comes in contact with alkaline solution [26]. This method avoids the use of unfavorable organic solvent used in emulsification method. However, it still has the drawback of the use of strong base which could compromise the activity of biomolecules. Besides, chitosan microparticles could also be obtained by the addition of a precipitant, i.e., sulfate to precipitate chitosan out from solution [27]. This method avoids the use of toxic organic solvents and glutaraldehyde which is used as a covalent cross-linked. But, the obtained particles by this method may have a weak mechanical property and irregular morphology.

 

d) Spray-drying

Spray-drying method is commonly used to produce powders, granules from the mixture of drug and excipient. The microparticles are obtained by the atomization of drug-excipient mixture in a stream of hot air or by immediate evaporation of excipient. Several parameters could affect the particle size, for instance, the nozzle size, spraying flow rate, atomization pressure, inlet air temperature and extent of cross-linking. For preparing chitosan microparticles, the drug could be dissolved or dispersed in chitosan solution followed by the addition of a proper cross-linking agent. Afterwards, this solution or dispersion is atomized in a stream of hot air which leads to instantaneous formation of free flowing particles [28].

 

 

MARKETED DRUGS WHICH HAVE BEEN MICROENCAPSULATED USING CHITOSAN

 

                                                                                                    Nifedipine

                               Diltiazem hydrochloride                                                Isosorbide-5-mononitrate

 

 

 

                                          Taxol

	MARKETED DRUGS MICROEN CAPSULATED USING CHITOSAN

 

                        Fluorouracil (5-FU)

 

 

 

            

                Diclofenac sodium                                                                                                                 Cisplastin                                                                                                                           

                                                          Ketoprofen                        Ibuprofen                        Indomethacin

                                                                                                                               

 

2 APPLICATIONS OF MICRO PARTICLES IN DRUG DELIVERY:

Here the applications of microparticles will be overviewed on the aspect of drug delivery.

 

2.1 Immune Adjuvants

Recently microparticles have been well developed as effective immune adjuvants. In order to realize a strong and lasting immune response, many vaccination formulations need the assistance of adjuvants since many antigens couldn’t produce sufficient immune responses themselves.

Generally microparticles could serve as immune adjuvants via enhancing and/or facilitating the uptake of antigens by antigen-presenting cells (APCs) such as dendritic cells (DCs) or macrophages; storing and controlling the release of loaded antigens, consequently increasing the availability of antigens to the immune cells; induce multiple immune responses by loading antigens combination; protecting sensitive antigen molecules from the degradation effect of surround environment and so on [29]. To date, many polymers [30], copolymers [31], and lipids [32] have been applied to produce microparticulate carriers of many kinds of antigen. Several important factors like particle size, morphology, particle surface properties, antigen loading and release kinetics of microparticles dramatically affect the induced immune responses in the sense of antigen stability, antigen release, particle interaction with APCs, antigen presentation and processing by APCs [33].

 

2.2 Ocular Drug Delivery

Microparticles have also been applied as ocular drug delivery system. The major objective of ocular therapeutics is to maintain sufficient drug concentration and residence time at the site of action. Whereas, the protective mechanisms such as rapid turnover, lacrimal drainage, reflex blinking, and drug dilution by tears lead to poor drug availability and permeation through corner. Considering the efficiency of conventional ophthalmic formulations like eye drops, suspensions, and ointments are badly compromised by the above mentioned physiological barrier, various modern approaches have been proposed. For instance, in situ gel, ocuserts, nanosuspension, microparticles, nanoparticles, liposomes, niosomes, and implants improve the ophthalmic bioavailability of the drugs and controlled the release of the ophthalmic drugs to the anterior segment of the eye [34]. Among them, Microparticles extend precorneal residence time, which leads to continuous and sustain release of the drug and consequently improve ocular bioavailability of the drug and reduced dosing frequency. Some natural or synthetic materials with good biodegradability, biocompatibility and bioadhesion like gelatin [35], chitosan [36] and hyaluronate esters [37] have been used to prepare these microparticles.

 

2.3 Pulmonary Drug Delivery

Pulmonary drug delivery (PDD) has several advantages which the pulmonary route offers over the others routes of drug administration, i.e. reduces first-pass metabolism or gastrointestinal degradation (such as proteins and peptides). In addition, less invasiveness and lower side effects of pulmonary administration increase patient compliance and reduce systemic exposure. However, PDD may have limitations due to a series of defenses of respiratory tract against inhaled materials such as mucociliary clearance, alveolar macrophages clearance, enzymatic metabolism and low permeability. All these barriers could lead to insufficient drug local concentration or bioavailability and consequently frequent drug administration is required. Particulate drug carriers such as liposomes, microparticles and nanoparticles can be/have been used to improve the therapeutic index of new or established drugs by modifying drug absorption, reducing metabolism, prolonging biological half-life or reducing toxicity[38].

 

2.4 Nanoparticles

Nanotechnology has been vastly applied in fiber and textiles, agriculture, electronics, forensic science, space and medical therapeutics. The application of nanotechnology in medicine gave the birth of a new concept—nanomedicine. To date, many nanomedicine formulations have been developed, i.e., nanoparticles, nanocapsules, micellar systems and dendrimers [39]. These nanoscaled formulations improve drug bioavailability, prolong drug in vivo circulating half-live and decrease drug size effect as a DDS. In addition, nanomedicine has specific advantages due to its nanoscaled size and targeted drug delivery is one of them.

 

2.5 Chitosan nano particles Preparation methods:

2.5.1 Ionic Gelation Method

Chitosan nanoparticles can be prepared by the interaction of oppositely charged macromolecules. Tripolyphosphate (TPP) has often been used to prepare chitosan nanoparticles because TPP is nontoxic, multivalent and able to form gels through ionic interactions. The interaction can be controlled by the charge density of TPP and chitosan, which is dependent on the pH of the solution. Nasti et al. (2009) [40] studied the influence of a number of factors, such as pH, concentration, ratios of components, and method of mixing, on the preparation of chitosan/TPP nanoparticles. Lin et al. (Lin et al., 2007) [41] investigated the relationship between free amino groups on the surface and the characteristics of chitosan nanoparticles prepared by the ionic gelation method. These factors were unaffected by TPP concentration in these references.

 

2.5.2 Reverse Micellar Method

Ultrafine polymeric nanoparticles with a narrow size range can be prepared with this method. The surfactant is dissolved in an organic solvent to prepare reverse micelles. An aqueous solution of chitosan is added with constant agitation to avoid any turbidity. The aqueous phase is regulated in such a way as to keep the entire mixture in an optically transparent micro emulsion phase. More water should be added if nanoparticles of a larger size are to be prepared. Brunel et al. (2008) [42] used a reverse micellar method to prepare chitosan nanoparticles. The lower the molar mass of chitosan, the better the control over particle size and size distribution, probably as a result of either a reduction in the viscosity of the internal aqueous phase or an increase in the disentanglement of the polymer chains during the process.

 

2.6 Medical Applications of Nanoparticles

Nanoparticles have been widely applied in therapeutics, diagnostics and imaging in medical and pharmaceutical fields. In therapeutics, surface-modified or multifunctional nanoparticles have been used to delivery various therapeutic drugs such as cancer therapeutics, vaccines, nucleic acids. They increase the effective drug concentration at desired diseased sites and decreased undesirable side effects of the current therapeutic. For example, the most frequently used chemotherapeutic antitumor drugs such as carboplatin, paclitaxel, doxorubicin and etoposide, etc., have been successfully loaded onto NPs and dramatically decrease their side effect to tumor-suffered patients. Molecular diagnostics and imaging emerged with the combination of nanomaterials, nanotechnology and modern advanced analysis instrumentation. The emergence of molecular diagnostics not only tremendously improves the medical diagnostic lever, provides more solid evidences for doctors, and also accelerates the development of cell and molecular biology. Nanoparticle is a major member of molecular diagnostics agents, i.e., gold (Au) NPs [43] and quantum dots (QDs). They are capable to detect cancer markers in blood assays or cancer tissue biopsies at pg/mL scale. On the other hand, the conjugation of various fluorescent molecules on nanoparticles could be as imaging agents to track and image nanoparticles from systemic to sub cellular lever.

 

3. Previous Research work on Chitosan:

Chitosan capsules for colon-specific delivery to treat ulcerative colitis. A 5-amino salicylic acid was encapsulated into Chitosan capsules and delivered in vivo to Male Wistar rats after induction of colitis. It was observed that Chitosan capsules disintegrated specifically in the large intestines as compared to the control formulation (in absence of Chitosan), which demonstrated absorption of the drug in small intestines. This data is a representative example of utility of Chitosan for colon-specific delivery [44].

 

During a study chitosan, nanoparticles including hydroxylpropylcyclodextrins prepared by the ionic cross linking of chitosan with sodium tripolyposphate in the presence of cyclodextrins. Two hydrophobic drugs, triclosan and furosemide, were selected as models for complexation with the cyclodextrin and further entrapment in the chitosan Nano carrier. The resulting Nano systems were thoroughly characterized for their size and zeta potential and also for their ability to associate and deliver the complexed drugs. So this new Nano system with chitosan offers an interesting potential for the transmucosal delivery of hydrophobic compounds [45]

 

Microcrystalline Chitosan (MCCh) may be particularly valuable as an excipient. As a highly crystalline grade of chitosan base. One specific property of MCCh is its high capacity for retaining water. This property could be advantageous in relation to the development of slow-release formulations because it might facilitate the formation of gels that would control drug release. The pronounced ability of MCCh to form hydrogen bonds could theoretically result in efficient mucoadhesion by MCCh. The properties of MCCh mentioned made it particularly interesting for study as a hydrophilic excipient-controlling rate of drug release from formulations that were also intended to be mucoadhesive in the stomach [46].

 

Intratumoral and local drug delivery strategies have gained momentum recently as a promising modality in cancer therapy. In order to deliver paclitaxel at the tumour site in therapeutically relevant concentration, Chitosan films were fabricated. Paclitaxel could be loaded at 31% wt/wt in films, which were translucent and flexible. Chitosan films containing paclitaxel were obtained by casting method with high loading efficiencies and the chemical integrity of molecule was unaltered during preparation according to study [47].

 

A quaternary derivative chitosan (N-trimethylene chloride Chitosan) was shown to demonstrate higher intestinal permeability than chitosan alone. The TMC derivative was used as a permeation enhancer for large molecules, such as octreotide, a cyclic peptide. Hamman and co-workers showed that the degree of quaternization of TMC influences its drug absorption-enhancing properties [48].

 

Chitosan and randomly methylated b-cyclodextrin (RAMEB) were the most to be studied absorption enhancers for nasal administration recently. From where it has clear that Chitosan and randomly methylated cyclodextrin could combine to enhance the absorption and elevate the bioavailability of estradiol after nasal administration [64].

 

A cationic polymer like chitosan has potential for DNA complexation and may be useful as non-viral vectors for gene therapy application. Chitosan is a natural non-toxic polysaccharide, it is biodegradable and biocompatible, and protects DNA against DNase degradation and leads to its condensation. Hence chitosan can be used to improve the transfection efficiency in vivo and in vitro [49].

 

3.1 Applications of Chitosan

3.1.1 Preliminary study on film dosage form prepared from chitosan for oral drug delivery:

The potential of chitosan films containing diazepam as an oral drug delivery was investigated in rabbits. The results indicated that a film composed of a 1:0.5 drug-chitosan mixture might be an effective dosage form that is equivalent to the commercial tablet dosage forms. The ability of chitosan to form films may permit its use in the formulation of film dosage forms, as an alternative to pharmaceutical tablets.

 

3.1.2 Increase stability of drug:

Chitosan polymer is use to increase the stability of the drug in which the drug is complexes with chitosan and make slurry and kneading for 45 min. until dough mass. This dough mass is pass through sieve no.16 and make a granules is completely stable at different condition.

 

3.1.3 Solubility increase as well as taste masking:

Chitosan and cyclodextrins mixed in equal amount and make complexes with drug. The complexes were characterized by SEM, XRPD, FT-IR, & DSC. These complexes were check solubility in incubating shaking with different solvent so we identified that complexes solubility is more to compare pure drug. Chitosan is bio compatible polymer use for taste masking and cyclodextrins having cavity like structure so drug inclusion complex in cyclodextrins and make a complete complexes so it was not release in saliva so its complexes were also used for the taste masking purpose.

 

3.1.6 Chitosan as Permeation Enhancer

It has been reported that chitosan, due to its cationic nature is capable of opening tight junctions in a cell membrane. This property has led to a number of studies to investigate the use of chitosan as a permeation enhancer for hydrophilic drugs that may otherwise have poor oral bioavailability, such as peptides. Because the absorption enhancement is caused by interactions between the cell membrane and positive charges on the polymer, the phenomenon is pH and concentration dependant. Furthermore increasing the charge density on the polymer would lead to higher permeability. This has been studied by quaternizing the amine functionality on chitosan. Further details are discussed in the chitosan derivatives section [50].

 

3.1.7 Chitosan as Mucoadhesive Excipient

Bioadhesivity is often used as an approach to enhance the residence time of a drug in the GI tract, thereby increasing the oral bioavailability. A comparison between chitosan and other commonly used polymeric excipients indicates that the cationic polymer has higher bioadhesivity compared to other natural polymers, such as cellulose, Xantham gum, and starch [51].

 

3.1.8 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 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. [53] 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. The duration of efficacy of the ofloxacin was increased by using high MW chitosan [54], [55].

 

4. CONCLUSION:

Biologically degradable polymers can be loosely distinct as a class of polymers, which degrade to smaller fragments due to chemical present inside the body. Natural polymers are always biodegradable because they undergo enzymatically promoted degradation. Chitosan is one of them, which exhibits biodegradability, scrawny antigenicity and better-quality biocompatibility compared with supplementary natural polymer. Chitosan has the desired properties for safe use as a pharmaceutical excipient. This has prompted accelerated research activities worldwide on chitosan micro and nanoparticles as drug delivery vehicles. These systems have great utility in controlled release and targeting studies of almost all class of bioactive molecules as discussed in this review. Recently, chitosan is also extensively explored in gene delivery. However, studies toward optimization of process parameters and scale up from the laboratory to pilot plant and then, to production level are yet to be undertaken. Majority of studies carried out so far are only in in-vitro conditions. In-vivo studies need to be carried out. Chemical modifications of chitosan are important to get the desired physicochemical properties such as solubility, hydrophilicity, etc.

 

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Received on 27.08.2014          Modified on 06.09.2014

Accepted on 10.09.2014         © RJPT All right reserved