Preparation And Characteristics Of PH-sensitive Derivated Dextran Hydrogel Nanoparticles

After Wichterleand and Lim's preparation of p-2-hydroxyethyl methacrylate (HEMA) hydrogel in 1960, hydrogel has been researched extensively because of its high water content, soft, mucosity and good biocompatibility et al. Hydrogel is divided into two kinds: synthetic pmer hydrogel, natural pmer hydrogel, according to materials. Nowadays, most hydrogel is made frome synthetic pmer. However, synthetic pmer hydrogel are not degradable in the body, which limited its application on clinics. Glycidyl methacrylate derivatized dextran (dex-GMA) and acrylic acid (AAc) were used to prepare hydrogel through copmerization. A new type of hydrogel having pH-sensitivity, partial degradability and mechanical strength was obtained. This study was to prepared nanogel by emulsion pmerization with modified dextran (dex) and (AAc) and study characteristics of obtained nanogel.1. Preparation of derived dextranGlycidyl methacrylate (GMA) was used to modify dex. The poduct was Glycidyl methacrylate derivatized dextran (dex-GMA). Degree of substitution (DS) was calculated by hydrogen nuclear magnetic resonance (HNMR) terms. DS of obtained products were 7, 10, and 13, respectively.2. Selection of optimized process of preparing nanogelP(dex-GMA/AAc) nanogel was prepared by radical pmerization reaction with dex-GMA and AAc. In this study emulsion pmerization was used to prepare nanogel, in order to filter the optimized process three continuous phase and three emulsifier. Three continuous phases were water, paraffin, and xylene (Xyl); three emulsifiers are Tween80, pethylene glycol (PEG), Span80. After comparison of the nanogel shape, particle diameter, encapsulation efficiency, drug loading efficiency, and so on indexes, finally the process using water as continuous phase and Tween80 as emulsifier was elected. The obtained nanogel showed spherical geometry and uniform appearance, with about 100 nm in size, encapsulation and drug loading efficiency were 90.7%, 1.06%, respectively.3. Characteristics of obtained nanogelDegradation behavior of nanogel was evaluated as mass loss of specimens in percent of initial dry weight. With the increase of AAc and DS of dex-GMA, degradation rate of nanogel became smaller. Size of nanogel in different pH was measured by laser scattering particle size distribution analyzer. At pH 1.2, the mean diameter of nanogel is about 60 nm; at higher pH 7.4 the mean diameter is about 260 nm. The dynamic dialysis was used to determine the drug release of nanogel in different pH value, erythromycin (EM) as model drug. In pH 1.2, pH 7.4 buffers, after 2 h cumulative release of nanogel is 7%, 18%, respectively. By ([3-(4, 5-dimethylthiazol-2-yl)] 2, 5-diphenyl tetrazolium bromide) (MTT) assay method the biocompatibility of nano-gel was evaluated, obtained results indicate that relative cell growth rate is over 90%.In conclusion, the size distribution and drug release profile at different pH demonstrated that P(dex-GMA/AAc) nanogel possessed pH-sensitivity. P(dex-GMA/AAc) nanogel could release EM slightly while passing through acerbic stomach, whereas in the alkaline intestine the drug is released considerably. This suggested that the P(dex-GMA/AAc) nanogel is potential colon-specific targeting carriers.4. Application of nanogel in wound dressingSustained release of P(dex-GMA/Aac) nanogel were introduced into KGM/CS film to maintain continuous release drug. Konjac glucomannan (KGM)/chitosan (CS) film containing EM-loaded nanogel was prepared by casting and solvent evaporation technique. This film became a gelatinous membrane, after the water was absorbed. The properties of the film for ideal wound dressing were examined, including equilibrium water content (EWC), water absorption (Aw), water vapor transmission rate (WVTR), and evaporative water loss of the film. Drug release of film containing nanogel or absent was compared; the biocompatibility was evaluated by MTT assay and hematoxylin and eosin (HE) stain method. Film was found to have equilibrium water content (EWC) 99.3% which could prevent exudates from accumulating and has excellent water adsorption, 2362.3±55.2%; the water vapor transmission rate (WVTR) was 2335±36 g.m-2.day-1 and evaporative water loss (EWL) was approximately 10% after 1 h and within 6 h it increased to 80%. These data indicated that the film could maintain moist environment of wound surface. Within 22 h, drug accumulative release of film containing nanoparticles or absent was 40.3%, 72.5% respectively. The results indicate that the obtained film containing nanogel had satisfactory biocompatibility and provide a continuous and sustained release of the antibacterial agent at the wound surface. The KGM/CS film containing P(dex-GMA/AAc) nanogel is potential ideal wound dressing.