Preparation and characterization of konjac glucomannan–poly(acrylic acid) IPN hydrogels for controlled release

In this paper, we reported the synthesis and properties of interpenetrating polymer network (IPN) hydrogel systems designed for colon targeted drug delivery. The gels were composed of konjac glucomannan (KGM) and cross-linked poly(acrylic acid) (PAA) by N,N-methylene-bis-(acrylamide) (MBAAm). It was possible to modulate the swelling degree of the gels. And the swelling ratio has sensitive respondence to the environmental pH value variation. The degradation tests show that the hydrogels retain the enzymatic degradation character of KGM. In vitro release of model drug VB₁₂ was studied in the presence of Cellulase E0240 in pH 7.4 phosphate buffer at 37 °C. The accumulative release percent of the model drug reached 85.6% after 48 h and the drug release was controlled by the swelling and the degradation of the hydrogels. The results indicated that the IPN hydrogels can be exploited as potential carriers for colon-specific drug delivery.     

Polyelectrolyte complexes of gum kondagogu and chitosan,as diclofenac carriers

Polyelectrolyte complexes (PEC) of gum kondagogu (GKG) and chitosan were prepared by mixing polymeric solutions of different concentrations (0.02–0.18% w/v). The complex formed were loaded with diclofenac sodium, and the release of the drug was measured in vitro and in vivo, along with the measurement of particle size, zeta potential, complex formation, flow properties, and loading efficiency. Maximum yield of PEC was observed at gum kondagogu concentrations above 80%. The PEC showed lower release of diclofenac sodium in 0.1 N HCl as compared to phosphate buffer (pH 6.8). Increasing the concentration of gum kondagogu in PEC led to an increase in drug release. However, PEC 1:3 (gum kondagogu: chitosan) with higher concentration of chitosan showed 98% release with in 4.5 h, owing to the fact that chitosan has a higher degree of swelling in acidic medium. PEC 5:1 and 3:1 showed a 5.3- and 5.8-fold increase in relative bioavailability compared to the free drug when administered orally to the rats.     

Synthesis and characterization of pH-sensitive hydrogel composed of carboxymethyl chitosan for colon targeted delivery of ornidazole

In the present study, carboxymethyl chitosan was prepared from chitosan, crosslinked with glutaraldehyde and evaluated in vitro as a potential carrier for colon targeted drug delivery of ornidazole. Ornidazole was incorporated at the time of crosslinking of carboxymethyl chitosan. The chitosan was evaluated for its degree of deacetylation (DD) and average molecular weight; which were found to be 84.6% and 3.5×10(4) Da, respectively. The degree of substitution on prepared carboxymethyl chitosan was found to be 0.68. All hydrogel formulations showed more than 85% and 74% yield and drug loading, respectively. The swelling behaviour of prepared hydrogels checked in different pH values, 1.2, 6.8 and 7.4, indicated pH responsive swelling characteristic with very less swelling at pH 1.2 and quick swelling at pH 6.8 followed by linear swelling at pH 7.4 with slight increase. In vitro release profile was carried out at the same conditions as in swelling and drug release was found to be dependant on swelling of hydrogels and showed biphasic release pattern with non-fickian diffusion kinetics at higher pH. The carboxymethylation of chitosan, entrapment of drug and its interaction in prepared hydrogels were checked by FTIR, (1)H NMR, DSC and p-XRD studies, which confirmed formation of carboxymethyl chitosan from chitosan and absence of any significant chemical change in ornidazole after being entrapped in crosslinked hydrogel formulations. The surface morphology of formulation S6 checked before and after dissolution, revealed open channel like pores formation after dissolution.     

Swelling behaviour of alginate–chitosan microcapsules prepared by external gelation or internal gelation technology

Swelling behaviour is one of the important properties for microcapsules made by hydrogels, which always affects the diffusion and release of drugs when the microcapsules are applied in drug delivery systems. In this paper, alginate–chitosan microcapsules were prepared by different technologies called external or internal gelation process respectively. With the volume swelling degree (S_w) as an index, the effect of properties of chitosan on the swelling behaviour of both microcapsules was investigated. It was demonstrated that the microcapsules with low molecular weight and high concentration of chitosan gave rise to low S_w. Considering the need of maintaining drug activity and drug loading, neutral pH and short gelation time were favorable. It was also noticed that S_w of internal gelation microcapsules was lower than that of external gelation microcapsules, which was interpreted by the structure analysis of internal or external gelation Ca–alginate beads with the aid of confocal laser scanning microscope.     

Microspheres of chitosan/carboxymethyl cashew gum (CH/CMCG): Effect of chitosan molar mass and CMCG degree of substitution on the swelling and BSA release

Chitosan/carboxymethyl cashew gum microspheres (CH/CMCG) were prepared with carboxymethyl cashew gum with two different degrees of substitution (DS) and loaded with bovine serum albumin (BSA). In water, for microspheres formed using low molar mass chitosan (LCH) sample swelling was observed for both CMCG samples and CMCG sample with higher DS showed greater swelling. Using high molar mass chitosan (HCH) sample swelling was observed only for microsphere with high DS of CMCG (DS = 0.44). At pH 7.4, the HCH sample led to a lower degree of swelling. The diffusion coefficients D_v were higher for the higher DS of CMCG in both media and the HCH sample had a lower D_v than LCH one. Faster BSA release rates were observed for beads prepared with the higher DS, whereas those prepared with DS = 0.16 took twice the time to reach similar release profiles. All microsphere systems investigated had a non-Fickian BSA release mechanism.     

Chitosan microcapsules loaded with either miconazole nitrate or clotrimazole,prepared via emulsion technique

In this paper, a simple and versatile coacervation technique has been developed by using an ultrasound-assisted oil/water emulsion method for the preparation of antifungal agent-loaded microcapsules. Two types of chitosan microcapsules are successfully prepared. The mean particle size of the chitosan/miconazole nitrate microcapsules is 2.6 μm and that of the chitosan/clotrimazole microcapsules is 4.1 μm. The encapsulation efficiency of the chitosan/miconazole nitrate microcapsules (77.58–96.81%) is relatively higher than that of the chitosan/clotrimazole microcapsules (56.66–93.82%). The in vitro drug release performance of the microcapsules shows that the chitosan/miconazole nitrate microcapsules release about 49.5% of the drug while chitosan/clotrimazole microcapsules release more than 66.1% of the drug after 12 h under a pressure of 5 kg at pH 5.5, which is similar to the pH of human skin. The prepared drug-loaded microcapsules could be applied onto bandages or socks, and will continuously release antifungal drugs in a controlled manner under pressure.     

Preparation and characterization of novel chitosan/gelatin membranes using chitosan hydrogel

Chitin and chitosan are novel biomaterials. The novel chitosan/gelatin membranes were prepared using the suspension of chitosan hydrogel mixed with gelatin. The prepared chitosan/gelatin membranes were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), mechanical, swelling, and thermal studies. The morphology of these chitosan/gelatin membranes was found to be very smooth and homogeneous. The XRD studies showed that the chitosan/gelatin membranes have good compatibility and interaction between the chitosan and gelatin. The stress and elongation of chitosan/gelatin membranes on wet condition showed excellent when the mixture ratio of gelatin was 0.50. The prepared chitosan/gelatin membranes showed good swelling, mechanical and thermal properties. Cell adhesion studies were also carried out using human MG-63 osteoblast-like cells. The cells incubated with chitosan/gelatin membranes for 24 h were capable of forming cell adhesion. Thus the prepared chitosan/gelatin membranes are bioactive and are suitable for cell adhesion suggesting that these membranes can be used for tissue-engineering applications. Therefore, these novel chitosan/gelatin membranes are useful for biomedical applications.     

Electric Field-Controlled Benzoic Acid and Sulphanilamide Delivery from Poly(Vinyl Alcohol) Hydrogel

The controlled release of benzoic acid (3.31 Å) and sulphanilamide (3.47 Å) from poly(vinyl alcohol), PVA, hydrogels fabricated by solution casting at various cross-linking ratios, were investigated. The PVA hydrogels were characterized in terms of the degree of swelling, the molecular weight between cross-links, and the mesh size. The drug release experiment was carried out using a modified Franz diffusion cell, at a pH value of 5.5 and at temperature of 37°C. The amount of drug release and the diffusion coefficients of the drugs from the PVA hydrogels increased with decreasing cross-linking ratio, as a larger mesh size was obtained with lower cross-linking ratios. With the application of an electric field, the amount of drug release and the diffusion coefficient increased monotonically with increasing electric field strength, since the resultant electrostatic force drove the ionic drugs from the PVA matrix. The drug size, matrix pore size, electrode polarity, and applied electric field were shown to be influential controlling factors for the drug release rate.KEY WORDS: electrophoresis force, ionic drug delivery, iontophoresis, poly(vinyl alcohol)     

One-step synthesis of interpenetrating network hydrogels: Environment sensitivities and drug delivery properties

A novel interpenetrating network hydrogel for drug controlled release, composed of modified poly(aspartic acid) (KPAsp) and carboxymethyl chitosan (CMCTS), was prepared in aqueous system. The surface morphology and composition of hydrogels were characterized by SEM and FTIR. The swelling properties of KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were investigated and the swelling dynamics of the hydrogels was analyzed based on the Fickian equation. The pH, temperature and salt sensitivities of hydrogels were further studied, and the prepared hydrogels showed extremely sensitive properties to pH, temperature, the ionic salts kinds and concentration. The results of controlled drug release behaviors of the hydrogels revealed that the introduction of IPN observably improved the drug release properties of hydrogels, the release rate of drug from hydrogels can be controlled by the structure of the hydrogels and pH value of the external environment, a relative large amount of drug released was preferred under simulated intestinal fluid. These results illustrated high potential of the KPAsp/CMCTS IPN hydrogels for application as drug carriers.     

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery

The covalently cross-linked chitosan-poly(ethylene glycol)₁₅₄₀ derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG₁₅₄₀-dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2 h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12 h. The results proved that the release-and-hold behavior of the cross-linked CS–PEG₁₅₄₀H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery.     

Synthesis of antibacterial PVA/CM-chitosan blend hydrogels with electron beam irradiation

A series of excellent hydrogels were prepared from poly(vinyl alcohol) (PVA) and carboxymethylated chitosan (CM-chitosan) with electron beam irradiation (EB) at room temperature. Electron spectroscopy analysis of the blend hydrogels revealed that good miscibility was sustained between CM-chitosan and PVA. The properties of the prepared hydrogels, such as the mechanical properties, gel fraction and swelling behavior were investigated. The mechanical properties and equilibrium degree of swelling improved obviously after adding CM-chitosan into PVA hydrogels. The gel fraction determined gravimetrically showed that a part of CM-chitosan was immobilized onto PVA hydrogel. The further analyses of FTIR and DSC spectra of the prepared gels after extracting sol manifested that there was a grafting interaction between PVA and CM-chitosan molecules under irradiation. The antibacterial activity of the hydrogels against Escherichia coli was also measured via optical density method. The blend hydrogels exhibited satisfying antibacterial activity against E. coli, even when the CM-chitosan concentration was only 3 wt%.     

Study of the near-neutral pH-sensitivity of chitosan/gelatin hydrogels by turbidimetry and microcantilever deflection

The fundamental properties and pH-sensitivity of chitosan/gelating hydrogels were investigated using spectroscopic and microelectro mechanical (MEMS) measurement approaches. Turbidimetric titration revealed that there were electrostatic attractive interactions between tripolyphosphate (TPP), chitosan, and gelatin in the acidic pH range, depending on their degree of ionization. The pH-sensitive swelling behavior of the hydrogels was investigated by monitoring the deflection of hydrogel-coated microcantilevers, which exhibited a sensitive and repeatable response to solution pH. The deflection of the microcantilever increased as the pH decreased, and the response speed of the system exhibited a nearly linear relationship with pH. The effects of the pH and concentration of TPP solution, as well as the ratio of chitosan to gelatin in gel precursor solutions, on the pH sensitivity of the hydrogels were also investigated. It was found that the swelling of the hydrogel is mainly a result of chain relaxation of chitosan-TPP complexes caused by protonation of free amino groups in chitosan, which depends on the crosslinking density set during the formation of the network. An increase in initial crosslink density induced a decrease in swelling and pH sensitivity. It can be concluded from this study that pH-sensitive chitosan gel properties can be tuned by preparatory conditions and inclusion of gelatin. Furthermore, microcantilevers can be used as a platform for gaining increased understanding of environmentally sensitive polymers.     

Polydimethylsiloxane modified chitosan. Part III: Preparation and characterization of hybrid membranes

The paper deals with the synthesis of organic–inorganic hybrid membranes, Hy, obtained by simultaneous grafting and crosslinking of chitosan with epoxy-terminated polydimethylsiloxane and γ-glycidoxypropyltrimethoxysilane. Porous membranes, HyP, were also obtained by acid decomposition, at different temperatures (25 and 50 °C), of calcium carbonate porogenic agent trapped inside the material. As proved by electron and atomic force microscopy, the non-porous membrane is a phase segregated material with spherical domains (10–40 μm) of silica core covered by hydrophobic siloxane in a hydrophilic chitosan matrix. The porous membranes showed different morphologies with irregular circular pores of 10–30 μm diameters for the membranes obtained at lower temperature, while the membranes prepared at 50 °C tend to adopt a plan-parallel porosity. The water contact angles of hybrid membranes (78°) and pure chitosan membranes (72°) indicated a lower hydrophilic character of modified chitosan. As a result of the crosslinking and of increased hydrophobicity, the hybrid membranes were characterized by a smaller water swelling degree (about 30%) as compared to pure chitosan membrane (700%). However, the presence of the pores in HyP membranes determined an increase of the water adsorption (maximum swelling degree, about 100%). The hybrid membranes possess a slightly higher thermal stability as compared to chitosan (first initial decomposition temperature, 147 and 175 °C for chitosan and hybrid membranes, respectively), but a lower one as compared to pure polydimethylsiloxane. The high storage modulus of chitosan (about 5.1 × 10⁹ Pa at 20 °C) is decreased by about one order of magnitude by the introduction of the highly flexible polysiloxane and the hybrid membranes are more flexible.     

Thermo-sensitive chitosan based semi-IPN hydrogels for high loading and sustained release of anionic drugs

Thermo-sensitive poly(N-isopropyl acrylamide-co-vinyl pyrrolidone)/chitosan [P(NIPAM-co-NVP)/CS] semi-IPN hydrogels with improved loading capacity and sustained release for anionic drugs NAP were prepared by free-radical polymerization. The LCST of hydrogels was adjusted to the vicinity of body temperature by introducing hydrophilic NVP. The presence of CS in semi-IPN networks improves the swelling behavior and provides a high affinity for anionic drug NAP due to the strong interactions between NAP molecules and CS chains. Release of NAP was suppressed at pH 2.2 and 5.0 and accelerated at pH 7.4 due to the deprotonation of amino groups in CS. Increasing temperature above LCST, hydrogels showed a continuous release of NAP without burst diffusion due to the shrinkage of PNIPAM restraining the drug release.     

Chemically cross-linked chitosan hydrogel loaded with gelatin for chondrocyte encapsulation

Composite hydrogels can be used as a scaffolding material for chondrogenesis, which requires a biomimetic environment to maintain chondrocyte morphology and phenotype. In this study, gelatin molecules were loaded into a hydrogel polymerized from a chitosan derivative (CML) to form a semi-interpenetrating polymer network. While the porous structure of the hydrogels in the dry state was not dependent on the gelatin content, the collapse extent and pore size decreased as the gelatin content increased. The gelatin loading also reduced the swelling ratio of the CML hydrogel and enhanced the hydrogel strength at 20°C due to gelation of the gelatin. The release behavior of the gelatin from the CML hydrogel could be controlled by many factors, such as the amount of gelatin, temperature, and solution pH. The weight loss of the composite hydrogel was expedited after gelatin loading and showed a positive relationship with the gelatin content. The results of in vitro cell culture in the hydrogels revealed that gelatin loading improved cell viability and promoted proliferation and glycosaminoglycans secretion of chondrocytes. This new scaffold production technology for chondrocyte encapsulation provides a further step towards CML applications in tissue engineering and other biomedical areas.     

Preparation and pharmacodynamics of low-molecular-weight chitosan nanoparticles containing insulin

Low-molecular-weight chitosan (LMWC) was obtained by enzymatic degradation and ultrafiltration separation. LMWC nanoparticles with LMWC having 20 kDa weight average molecular weight (M_w) were then prepared by solvent evaporation method. The resultant nanoparticles were spherical with a narrow particle size distribution. LMWC nanoparticles loaded with insulin as a model drug were prepared. The average entrapment efficiency of insulin could reach up to 95.54%. The in vitro drug release profiles from the nanoparticles showed an initial burst of release in the first 2 h, followed by zero order release kinetics. In vivo pharmacodynamics of chitosan nanoparticles containing insulin showed that the nanoparticles showed some hypoglycemic activity. Compared with an insulin solution, a relative bioavailability of 0.737 was observed for four times the dosage of insulin in the chitosan nanoparticles after pulmonary administration.     

Effect of PVA on the gel temperature of MC and release kinetics of KT from MC based ophthalmic formulations

The effect of molecular weight of poly(vinyl alcohol) (PVA) and sodium chloride on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ketorolac tromethamine a model ophthalmic drug. Pure MC showed sol-gel transition at 61.2 °C. In order to reduce the gelation temperature of MC and to increase the drug release time, PVA was used. Different techniques such as test tube tilting method, UV-vis spectroscopy, viscometry and rheometry were used to measure gelation temperature of all the binary combinations of MC and PVA. It was observed that the gelation temperature of MC was reduced with the addition of 4% PVA and also the extent of reduction of the gelation temperature of MC was dependent on the molecular weight of PVA. The strong interactions between MC and PVA molecules were established using Fourier transform infrared spectroscopy. To study the in vitro drug release properties of the MC-PVA binary combinations, 6% sodium chloride was used to reduce the gelation temperature further up to physiological temperature. It was observed that the drug release time increased from 5 to 8h with the increase of molecular weight of PVA from 9×10(3) to 1.3×10(5) and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3×10(5)) compared to PVA (9×10(3)). In order to have an idea about the nature of interactions between the functional moieties of the drug and the polymer unit of PVA, a theoretical study was carried out.     

Xanthan-g-poly(acrylamide): Microwave-assisted synthesis,characterization and in vitro release behavior

Xanthan-g-poly(acrylamide) was synthesized employing microwave-assisted and ceric-induced graft copolymerization, and was characterized by FT-IR, DSC, XRD and SEM studies. Matrix tablets of diclofenac sodium were formulated using graft copolymer as the matrix by direct compression technique. Release behavior of the graft copolymer was evaluated using USP type-II dissolution apparatus in 900 ml of phosphate buffer (pH 6.8), maintained at 37 °C and at 50 rpm. Microwave-assisted grafting provided graft copolymer with higher % grafting in a shorter time in comparison to the ceric-induced grafting. The % grafting was found to increase with the increase in the power of microwave and/or time of exposure. The matrix tablets were found to release the drug by zero-order kinetics, and the faster release of drug was observed from the graft copolymer matrix as compared to the xanthan gum matrix. It was observed that grafting reduces the swelling, but increases the erosion of xanthan gum.     

Preparation of vinylated polysaccharides and photofabrication of tubular scaffolds as potential use in tissue engineering

Polysaccharides, such as heparin, hyaluronan, and chitosan, were partially derivatized with a styryl or a methacryloyl group by condensation at a carboxyl or an amino group of the polysaccharides with 4-vinylaniline or 4-vinylbenzoic acid. The degree of substitution depended on the reaction conditions. These compounds with low degrees of derivatization produced water-swollen hydrogels only at relatively high concentrations (30-40 wt %) in the presence of a carboxylated camphorquinone upon visible light irradiation. A high degree of derivatization of heparin increased the gel yield and concomitantly reduced the degree of swelling. The copolymerization of these vinylated polysaccharides with styrenated gelatin considerably reduced the degree of swelling. Tubular photoconstructs were prepared by photocopolymerization of vinylated polysaccharide and vinylated gelatin. The mixing of diacrylated poly(ethylene glycol) with vinylated polysaccharide improved the burst strength of photogels against the gradual infusion of water. These photocurable polysaccharides may be used as photocured scaffolds in tissue-engineered devices.     

Photopolymerization of methacrylated chitosan/PNIPAAm hybrid dual-sensitive hydrogels as carrier for drug delivery

A series of hybrid hydrogels based on glycidyl methacrylated chitosan (CS-GMA) and N-isopropylacrylamide (NIPAAm) were designed and prepared via photopolymerization technology. The hydrogels were characterized by Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and optical transmittance. The interior morphology of hydrogels was investigated by scanning electron microscopy (SEM). The swelling experiment results revealed that hybrid hydrogel exhibited combined pH and temperature sensitivities. Acid orange 8 (AO8) and 5-flurouracil (5-Fu) were selected as model drugs for examining their release from hydrogels. The results suggested that hydrogel composition and pH value of buffer solution had great influences on release profiles.