Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications

Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

https://tandfonline.com/doi/pdf/10.1080/10717544.2017.1279238

pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms

In the present work, a series of cross-linked LVCS/PVA hydrogels with various feed compositions were prepared using glutaraldehyde as cross-linking agent. The prepared hydrogels were used for dynamic and equilibrium swelling studies. The swelling behavior of these hydrogels was investigated as functions of effect of pH, polymeric compositions and degree of cross-linking. Swelling studies were performed in 0.05 M USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing PVA contents in the structure of hydrogels in solutions of higher pH values. This is due to the presence of more hydroxyl groups (–OH) in the PVA structure. On the other hand, by increasing LVCS contents, swelling increased in a solution of acidic pH and it is due to ionization of amino groups (–NH2), but this swelling was not significant. Swelling of hydrogels was decreased with increase in cross-linking ratio due to tighter hydrogel structure. Porosity and sol–gel fraction were also investigated. It was found that with increase in LVCS and PVA contents porosity and gel fraction increased, whereas by increasing glutaraldehyde content gel fraction increased and porosity decreased. Diffusion coefficient (D) and network parameters, i.e., the average molecular weight between cross-links (MC), solvent interaction parameters (χ), polymer volume fraction in swollen state (V2S) and cross-linked density (q) were calculated using Flory–Rehner theory. Selected samples were loaded with model drug diphenhydramine HCl. The release of diphenhydramine HCl was studied for 12 h period in 0.05 M USP phosphate buffer solutions of varying pH 1.2, 5.5 and 7.5. It was observed that drug release increased with increasing PVA contents in the hydrogels, while release of drug decreased as the ratio of cross-linking agent increased in the hydrogel structure owing to strong physical entanglements between polymers. The release mechanisms were studied by fitting experimental data to model equations like zero order, first order, Higuchi and Peppas. Results showed that the kinetics of drug release from hydrogels in buffer solutions of pH 1.2, 5.5 and 7.5 was mainly non-fickian diffusion. Hydrogels were characterized by Fourier transform infrared and X-ray diffraction to confirm the structure and study the crystallinity of hydrogel, respectively.

Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly(vinyl alcohol) hydrogels

This present work was aimed at synthesizing pH-sensitive cross-linked AA/Gelatin hydrogels by free radical polymerization. Ammonium persulfate and ethylene glycol dimethacrylate (EGDMA) were used as initiator and as cross-linking agent, respectively. Different feed ratios of acrylic acid, gelatin, and EGDMA were used to investigate the effect of monomer, polymer, and degree of cross-linking on swelling and release pattern of the model drug. The swelling behavior of the hydrogel samples was studied in 0.05 M USP phosphate buffer solutions of various pH values pH 1.2, pH 5.5, pH 6.5, and pH 7.5. The prepared samples were evaluated for porosity and sol-gel fraction analysis. Pheniramine maleate used for allergy treatment was loaded as model drug in selected samples. The release study of the drug was investigated in 0.05 M USP phosphate buffer of varying pH values (1.2, 5.5, and 7.5) for 12 hrs. The release data was fitted to various kinetic models to study the release mechanism. Hydrogels were characterized by Fourier transformed infrared (FTIR) spectroscopy which confirmed formation of structure. Surface morphology of unloaded and loaded samples was studied by surface electron microscopy (SEM), which confirmed the distribution of model drug in the gel network.

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Synthesis and Characterization of Chemically Cross-Linked Acrylic Acid/Gelatin Hydrogels: Effect of pH and Composition on Swelling and Drug Release

The aim of present study was to determine the efficacy of polyacrylic acid-based and chitosan-based hydrogels (synthesized via chemical crosslinking) for the adsorption and removal of cadmium contained in aqueous solutions. Reactive functional groups involved in the adsorption of cadmium were confirmed by Fourier-transform infrared spectroscopy and cadmium adsorbed to the hydrogel surface was confirmed by scanning electron microscopy coupled to energy-dispersive X-ray spectroscopy. The cadmium adsorption mechanism was evaluated using non-linear Langmuir, Freundlich, Redlich-Peterson and Sips isotherms, with the best fits found using the non-linear Sips and Redlich-Peterson isotherms for adsorption to polyacrylic acid-based and chitosan-based hydrogels, respectively. Maximum cadmium adsorption capacities of the polyacrylic acid-based and chitosan-based hydrogels were respectively 197.92 and 234.84 mg of metal per g of dried hydrogel at pH 6.0 and 343.0 ± 1.0 K. The best kinetic fit for adsorption to the chitosan-based hydrogel was found with the pseudo-second order kinetic model, whereas the best kinetic fit for adsorption to the polyacrylic acid-based hydrogel was found with the pseudo-first order kinetic model. The thermodynamic results indicated that the adsorption of cadmium to both hydrogels is a favorable, spontaneous process. The desorption studies suggested the formation of reversible chemical bonds between cadmium and active groups in the hydrogel network.

Polyacrylic acid-based and chitosan-based hydrogels for adsorption of cadmium: Equilibrium isotherm, kinetic and thermodynamic studies

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (Mc), polymer volume fraction in swollen state (V2s), number of repeating units between crosslinks (Mr) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

Introduction: Amphiphilic copolymers are capable of forming core shell-like structures at the critical micellar concentration (CMC); hence, they can serve as drug carriers. Thus, in the present work, polymeric micelles based on novel chitosan derivative were synthesized. Methods: Block copolymer of palmitoyl glycol chitosan sulfate (PGCS) was prepared by grafting palmitoyl and sulfate groups serving as hydrophobic and hydrophilic fractions, respectively. Then, fourier transform infrared spectra (FTIR) and spectral changes in iodine/iodide mixture were carried out. Results: FTIR studies confirmed the formation of palmitoyl glycol chitosan sulfate (PGCS) and spectral changes in iodine/iodide mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. Conclusion: Therefore, our study indicated that polymeric micelles based on palmitoyl glycol chitosan sulphate could be used as a prospective carrier for water insoluble drugs. A B S T R A C T A R T I C L E I N F O

Gohar Ayub

Papers

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

Assessment of Palmitoyl and Sulphate Conjugated Glycol Chitosan for Development of Polymeric Micelles