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Synthesis and Characterization of New Materials for Drug Slow Release

Author: GuoWenXun
Tutor: HuangKaiXun
School: Huazhong University of Science and Technology
Course: Biomedical Engineering
Keywords: biodegradable polymer unsaturated polyester Polyanhydride S180 tumour drug sustaining-release biocompatibility local chemotherapy ciprofloxacin hydrochloride gentamicin sulfate adriamycin hydrochloride 5-fluorouracil
CLC: R318.08
Type: PhD thesis
Year: 2004
Downloads: 921
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Abstract


Polyesters and polyanhydrides come under an increasingly recognition in medical application. In this article a new kind of injectable drug controlled release material of unsaturated polyester and several new type of polyanhydrides have been prepared by using C12~15 dibasic acids and other corresponding monomers, they have desired biocompatibility, absorbable biodegradability in vivo and bioactivity after mixed drugs. The main results are as follows:.1. Poly(dimer acid-dodecanedioic acid) copolymer, poly(dimer acid-brassylic acid) copolymer, poly(dimer acid-tetradecanedioic acid) copolymer and poly(dimer acid-pentadecanedioic acid) copolymer were prepared by melt polycondensation by using C12~15 dibasic acid copolymerized with dimer acid respectively, poly(dodecanedioic acid- tetradecanedioic acid) copolymer and poly(brassylic acid - pentadecanedioic acid) copolymer were also prepared by using prepolymer of C12~15 dibasic acid respectively. The copolymers in vitro degradation, drug release profiles of hydrophilic model drug, ciprofloxacin hydrochloride, from the copolyanhydrides in 0.1mol/L pH7.4 PBS at 37℃ were also investigated. The copolymers were characterized by FT-IR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), wide angle X-ray powder-diffraction, and thermal gravimetric analysis (TGA) etc. In vitro degradation, drug release profiles of hydrophilic model drug, ciprofloxacin hydrochloride,from the copolyanhydrides in 0.1mol/L pH 7.4PBS at 37℃ were also investigated. It showed that all the prepared copolyanhydrides meet the essential requirement for polyanhydrides as drug delivery material including high molecular weights, low melting points, and desired thermal stability. In vitro release profiles of gentamicin sulfate and ciprofloxacin hydrochloride from the copolyanhydrides showed relatively steady drug release rate, and followed first order release kinetics as a whole,in some definite monomer ratio conditions the release profiles followed zero order release kinetics,The in vitro degradable characterization of all the copolymers showed the desired erosion rate for drug release. The erosion rate and drug release rate seems in reverse to the content of DA and the degree of crystallinity. The synthesized polyanhydrides were preliminarily injected under mice skin, and the microscopically histopathologic observations revealed that the copolymers produced responses gently than the control, absorbable gelatin sponge. Preliminary in vivo studies under mice skin showed that adriamycin hydrochloride-polyanhydride controlled release preparation can be absorbed completely <WP=7>and no drugs can be checked out in blood of heart. The polymers possess good tissue compatibility,animal degradability and have proper standing drug release profiles and good security of drug release. 2. In vitro bacteriostatic activity of gentamicin sulfate-polyanhydride and in vivo anti-tumor activity of adriamycin hydrochloride-polyanhydride wafer were preliminarily determined. In vitro bacteriostatic activity studies demonstrated that the beads containing 5% gentamicin sulfate possessed desired bacteriostatic activity, and lasted for 45-60 days for staphylococcus aureus and escherichia coli, which are common bacteria for infections in bone, suggest that the biodegradable sustained-release beads may be promise as a new treatment device for osteomyelitis treatment. In vivo studies showed that antitumor efficacy of polyanhydride(150mg) containing 5% adriamycin hydrochloride in Sarcoma-180 mice bearing tumor exhibited increased volume doubling time between 24~35 days compared to plain subcutaneous injection of adriamycin hydrochloride (7days). All above demonstrated that the novel sustained-release wafer may be promising for the treatment of noumenon tumor. 3. The new unsaturated polyester resins were prepared by melt polycondensation of the corresponding mixed monomers: sebacic acid or C12~13 dibasic acid, fumaric acid or maleic anhydride and glycol. They were Poly(maleic anhydride-glycol-sebacic acid) cop

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CLC: > Medicine, health > Basic Medical > Medical science in general > Biomedical Engineering > General issues > Biomaterial
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