Chitosan-based Carriers Research Articles

Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid.

Gene therapy is an emerging therapeutic strategy for the cure or treatment of a spectrum of genetic disorders. Nevertheless, advances in gene therapy are immensely reliant upon design of an efficient gene carrier that can deliver genetic cargoes into the desired cell populations. Among various nonviral gene delivery systems, chitosan-based carriers have gained increasing attention because of their high cationic charge density, excellent biocompatibility, nearly nonexistent cytotoxicity, negligible immune response, and ideal ability to undergo chemical conjugation. However, a major shortcoming of chitosan-based carriers is their poor cellular uptake, leading to inadequate transfection efficiency. The intrinsic feature of cell penetrating peptides (CPPs) for transporting diverse cargoes into multiple cell and tissue types in a safe manner suggests that they can be conjugated to chitosan for improving its transfection efficiency. In this review, we briefly discuss CPPs and their classification, and also the major mechanisms contributing to the cellular uptake of CPPs and cargo conjugates. We also discuss immense improvements for the delivery of nucleic acids using CPP-conjugated chitosan-based carriers with special emphasis on plasmid DNA and small interfering RNA.

Advances in the Targeting Molecules Modified Chitosan-Based Nanoformulations

Chitosan, a cationic polysaccharide, has prompted the continuous impetus for the development of safe and effective drug delivery systems due to its unique properties such as mucoadhesive feature, absorption enhancement and active functional groups for chemical modifications. By using chitosan-based nanoformulations, many studies have attempted to improve the dispersion of loaded hydrophobic drugs in aqueous environment, protect the encapsulated proteins and genes against enzymatic degradation, and increase their absorption by target tissues. It's noteworthy that the derivatization of chitosan-based carriers with a ligand leads to the selective targeting of the nanoformulations to selected cells, thereby facilitating far more sensitive internalization and localization of nanoformulations for diseases' diagnosis and treatment. As such, this review focuses on some of the most poignant reports of the utility of targeting molecules such as carbohydrates, antibodies, peptides and some small molecules in chitosan-based nanoformulations for targeted delivery. Additionally, the affinity mechanism of different targeting molecules and the pros and cons of their conjugation strategies will be illustrated summarily.

The potential of chitosan for pulmonary drug delivery

The administration of drugs through the pulmonary route offers great advantages, but it also requires overcoming many challenges. There is a need to develop appropriate carriers to deliver active molecules to their desired sites in the lung for either a local or a systemic effect. The polysaccharide chitosan is a very promising material for this purpose, given its demonstrated properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation. In this review, the potential of chitosan for the development of drug carriers for the lung will be discussed. The most important features that support its selection will be explained. Additionally, different approaches to increase its performance, especially its solubility, its permeation-enhancing properties and gene transfection efficiency will be presented. Special emphasis will be placed on information on different chitosan-based carriers, namely nanoparticles and microparticles, intended for pulmonary drug delivery.

Enhanced Topical Delivery of Terbinafine Hydrochloride with Chitosan Hydrogels

Chitosan-based carriers have important potential applications for the administration of drugs. In the present study, topical gel formulations of terbinafine hydrochloride (T-HCl) were prepared using different types of chitosan at different molecular weight, and the antifungal inhibitory activity was evaluated to suggest an effective formulation for the treatment of fungal infections. The characteristics of gel formulations were determined with viscosity measurements and texture profile analysis. Stability studies were performed at different temperatures during 3 months. The ex vivo permeation properties were studied through rat skin by using Franz diffusion cells. The antifungal inhibitory activity of formulations on Candida species and filamentous fungi was also examined with agar-cup method. The microbiological assay was found suitable for determination of in vitro antifungal activity of T-HCl. A marketed product was used to compare the results. The antifungal activity of T-HCl significantly increased when it was introduced into the chitosan gels. A higher drug release and the highest zone of inhibition were obtained from gels prepared with the lowest molecular weight chitosan (Protasan UP CL 213) compared to that of other chitosan gels and marketed product. These results indicated the advantages of the suggested formulations for topical antifungal therapy against Candida species and filamentous fungi.

Preparation and properties of a chitosan-based carrier of corneal endothelial cells

A novel chitosan-based membrane that was made of hydroxypropyl chitosan, gelatin and chondroitin sulfate was used as a carrier of corneal endothelial cells. The characteristics of the blend membrane, such as transparency, equilibrium water content, permeability, mechanical properties, protein absorption ability, hydrophilicity and surface morphology, were determined. To study the effects of the membrane on cell attachment and growth, rabbit corneal endothelial cells were cultured on this artificial membrane. The biodegradability and biocompatibility of the blend membrane were in vivo evaluated by its implantation into the muscle of the rats. Glucose permeation results demonstrated that the blend membrane had higher glucose permeability than natural human cornea. Scanning electron microscopy (SEM) analysis of the membranes demonstrated that no fibrils were observed. As a result, the optical transparency of the membrane was as good as the natural human cornea. The average value of tensile strength of the membrane was 13.71 MPa for dry membrane and 1.48 MPa for wet membrane. The value of elongation at break of the wet was 45.64%. The cultured rabbit corneal endothelial cells formed a monolayer on the blend membrane which demonstrated that the membrane was suitable for corneal endothelial cells to attach and grow. In addition, the membranes in vivo showed a good bioabsorption property. The mild symptoms of inflammation at sites of treatment could be resolved as the implant was absorbed by the host. The results of this study demonstrated that the hydroxypropyl chitosan-chondroitin sulfate-gelatin blend membrane can potentially be used as a carrier for corneal endothelial cell transplantation.

Immobilized Alkaline Phosphatase for Molecular Cloning

Alkaline phosphatase from E. coli was immobilized on Sepharose-4B, macroporous cellulose and chitosan-based carriers. The yields of immobilization were over 60% in most cases. It was shown that immobilized alkaline phosphatase can be used for dephosphorylation of DNA 5'-termini.