黏膜黏附性可注射布丁型复合水凝胶膀胱灌注给药系统

批准号:
21965021
项目类别:
地区科学基金项目
资助金额:
40.0 万元
负责人:
彭志平
依托单位:
学科分类:
医用材料化学
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
彭志平
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中文摘要
针对膀胱灌注化疗中存在的药物停留时间短、黏膜渗透性差和难于精确定位病灶区给药等不足,围绕有效调控给药系统与膀胱黏膜的相互作用这一关键科学问题,设计构建黏膜黏附性的“布丁”型可注射复合水凝胶膀胱灌注给药系统:以黏膜黏附的巯基化壳聚糖(CS-SH)作为凝胶骨架,定点于病灶部位灌注,利用凝胶化动力学可控的酶催化交联反应包埋载药的壳聚糖/PluronicF127(CS/PF127)纳米凝胶,原位快速形成复合凝胶。由黏膜黏附的水凝胶基体将载药纳米凝胶定位于病灶部位,结合复合水凝胶对药物的多层次控释和壳聚糖可暂时性削弱膀胱黏膜渗透屏障的生理功能,有效地提高药物在膀胱黏膜的停留时间和渗透性。通过调控给药系统的结构、黏膜黏附性和药物释放动力学,并结合细胞实验和膀胱内灌注实验,实现膀胱内定点、长效时控型灌注化疗,为膀胱内载药系统的设计与制备提供创新思路,为浅表性膀胱肿瘤术后治疗和临床前研究提供实验基础。
英文摘要
The current intravesical drug delivery systems for chemotherapy of superficial or non-muscle invasive bladder cancers exhibit some inherent drawbacks, such as short residence time and low penetration of the drug within the bladder, imprecise lesion location control during the therapeutic process. These shortcomings result in a need for frequent drug instillation. Development of novel intravesical drug delivery systems to enhance the interaction between the drug carriers and bladder mucosal, improve the penetration of drugs into the bladder wall are crucial to overcome these drawbacks. The object of this project is to design, preparation, in vitro and in vivo characterization of a novel mucoadhesive injectable plum-pudding composite hydrogel for the application in intravesical instillation chemotherapy of superficial bladder cancer. A core-shell drug-loaded chitosan/Pluronic F127 (CS/PF127) nanogel will be synthesized by the combination of emulsification/solvent evaporation method and thiol-maleimide click between maleimide functioned PF 127(mal-PF127-mal) and thiolated chitosan (CS-SH). A mucoadhesive composite hydrogel with controlled gelation rate and network structure is formed by embedding the drug-loaded CS/PF127 nanogel using thiolated chitosan via enzymatically crosslinking reaction. The composite hydrogel is in suit formed rapidly at lesion location by instilling precisely the precursor solution to the lesion location. The drug-loaded nanogel is located at lesion location which was controlled by the mucoadhesive composite hydrogel. The release of loaded-drug in composite hydrogel will be controlled by both nanogel and hydrogel and the time-controlled release profile is expected. Combined multilevel controlled release of drug and the capability of chitosan to transitorily abolish the barrier function of urothelium, we hypothesize that the mucosdhesive plum pudding composite hydrogel would result in prolonged drug residence time, improved penetration of the drug within the bladder and enhanced antitumor activity. The mucoadhesion and the property of controlled drug release will be tailored by controlling the structure of composite hydrogel. We believe that the novel injectable plum pudding composite hydrogel intravesical drug delivery systems will effectively prevent recurrent and disease progression of superficial bladder cancers. A site-specific and sustained time-controlled release of loaded drug will be obtained. The purpose of this project is to provide an innovative idea for designing and developing of intravesical drug delivery systems to improve the therapeutic effect of superficial bladder cancers. This project will generate key experimental basis and research samples for further preclinical application in the treatment of superficial bladder cancer.
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DOI:10.1016/j.electacta.2024.143785
发表时间:2024-01
期刊:Electrochimica Acta
影响因子:6.6
作者:Haichao Xu;Qing Wang;Yinyan Deng;Zhiping Peng;Tao Wang
通讯作者:Haichao Xu;Qing Wang;Yinyan Deng;Zhiping Peng;Tao Wang
DOI:--
发表时间:2022
期刊:精细化工
影响因子:--
作者:袁帆;廖曦;陈献煌;彭志平
通讯作者:彭志平
酶固定化的杂化微凝胶的可控制备及其吸附与降解染料研究
- 批准号:21664010
- 项目类别:地区科学基金项目
- 资助金额:40.0万元
- 批准年份:2016
- 负责人:彭志平
- 依托单位:
基于载药微胶囊构筑的多孔复合水凝胶和电纺纤维的制备及其蛋白质控释应用
- 批准号:51263017
- 项目类别:地区科学基金项目
- 资助金额:50.0万元
- 批准年份:2012
- 负责人:彭志平
- 依托单位:
蛋白质药物控释载体用可生物降解水凝胶的合成及其时控型释药特性研究
- 批准号:51003046
- 项目类别:青年科学基金项目
- 资助金额:20.0万元
- 批准年份:2010
- 负责人:彭志平
- 依托单位:
国内基金
海外基金
