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Synthesis, Characterization and Application in Drug Release of pH-and Tempareture-sensitive Hydrogel Beads/microparticles

Author: MaLiWei
Tutor: LiuMingZhu
School: Lanzhou University
Course: Polymer Chemistry and Physics
Keywords: Carboxymethyl chitosan Poly (N- vinyl pyrrolidone) Poly ( N , N - diethyl acrylamide ) Polymethyl methacrylate pH-sensitive Temperature sensitivity Microspheres Microgel Microcystis Micelle Critical phase transition Atom transfer radical polymerization Free emulsion polymerization Graft copolymer Drug release
CLC: R94
Type: PhD thesis
Year: 2010
Downloads: 821
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Abstract

This thesis carboxymethyl chitosan (CMCTS) and methacrylic acid (MAA) as the pH-sensitive functional monomer, N, N-diethyl acrylamide (DEA) to the temperature sensitive functional monomer, using different experimental methods were prepared having different sizes of the spherical structure of the gel; by changing the structure of the polymer and the composition to adjust the release rate of the drug-loaded gel in different physiological environments; through the gel biocompatible The preliminary study shows a good prospect in clinical oral drug carrier, especially targeting drug intestinal. The main results are: 1. Radical solution polymerization method, the synthesis of a series can be dissolved in an alkaline solution of carboxymethyl chitosan-graft-poly-N-vinyl pyrrolidone (CMCTS-g-PVP) polymerization objects, using the method of crosslinking of the ion obtain desired gel particles; swelling experiments showed that the gel particles have a significant pH sensitivity; VB2 drug release results show that the gel particles in a buffer solution of pH = 1.2 in the drug release rate was significantly lower than at pH = 7.4 when the drug release rate: graft ratio by increasing the concentration of crosslinker and CMCTS-g-PVP, can significantly reduce the release rate of the drug-loaded particles. 2 on the basis of the above work, synthetic series having different graft rates carboxymethyl chitosan-graft-poly-N, N-diethyl acrylamide (CMCTS-g-PDEA) polymer, crosslinking, in a mixed solution of HCl and CaCl2 to obtain the gel particles having a dual crosslinked key structure; swelling experiments showed that the hydrogel particles having a pH sensitivity and temperature sensitivity, and due to its double cross linked structure and high grafting rate, the gel particles at pH = 7.4 The medium is relatively stable; contrast simply using the calcium ion cross-linked gel particles and containing a double cross-linked bond structure of the gel particles in vitro drug release behavior, indicating that the drug-loaded particles with a double cross-linked network structure and its release is better than a single drug-loaded particles crosslinked; elevated temperature and increase the rate of graft CMCTS-g-PDEA graft, could significantly reduce the release rate of the drug-loaded particles. 3 using a soap-free emulsion polymerization method, is prepared in an aqueous solution having a core-shell structure of the P (DEA-co-MAA) hydrogel microspheres; TEM photos show that the gel particles having a core-shell structure; improve the solution pH value, P (DEA-co-MAA) microgels hydrodynamic diameter (Dv) at different pH environment significantly increased, increase in the amount and with MAA, particle diameter gradually increases; With the amount of the microsphere system MAA the increase of the volume of the hydrogel microspheres phase transition temperature (LCST) is gradually increased, and accessible the physiological temperature of the human body; drug release results show that P (DEA-co-MAA) micro ball than PDEA microspheres having better slow release effect, and the drug delivery system can reduce the bovine serum albumin (BSA) released in the gastric fluid, is released in the intestine positioning application prospect; cytotoxic experimental results demonstrate, P (DEA-co-MAA) has a good biocompatibility, is expected to be applied to the field of biomedicine. 4 prepared by the simple method of self-assembled CMCTS-g-PDEA microgel microcapsules and microparticles two forms can be obtained by the graft rate of change, the smaller the size of the microgel; drug release at different pH values, results showed micro-gel in the acidic environment of the drug release rate was significantly lower than the release rate in alkaline environment, while the micro-structure of the gel has a great influence on the drug release rate, the microgel having a vesicle structure, the The drug release rate is slowed, with the graft ratio increases while the cytotoxicity assay results for the particle shape of microgels, although having a higher grafting rate, but due to its network crosslink density, the rate of drug release; prove the drug delivery system, non-toxic, has good biocompatibility, and certain role in promoting cell proliferation, has good prospects used in the field of bio-medicine. 5 by atom transfer radical polymerization technique to prepare a triblock polymer of PHEMA-b-PDEA-b-PHEMA, the polymeric micelles in aqueous solutions can be self-assembled to form a uniform particle size of the nano-micelles, and the polymer lower critical micelle concentration of micelles; the loaded micelles vitro release kinetics study show that the the loaded micelles release process has a significant temperature response, the positioning of such drug delivery systems for injectable drug release certain application prospects.

Synthesis, Characterization and Application in Drug Release of pH-and Tempareture-sensitive Hydrogel Beads/microparticles

Abstract

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