BIOADHESIVE MICROSPHERES

生物粘附微球

• 批准号: 6386332
• 负责人: Edith Mathiowitz
• 金额: $ 29.94万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6386332
• 关键词: acidity /alkalinity; alpha benzopyrone; biomaterial development /preparation; biomaterial interface interaction; biotransformation; cell adhesion; copolymer; drug delivery systems; drug design /synthesis /production; drug metabolism; endoscopy; high performance liquid chromatography; hydropathy; intestinal mucosa; laboratory rat; microcapsule; oral administration; paclitaxel; pharmacokinetics; polymers; scanning electron microscopy; spectrometry; swine; temperature; tensile strength

We propose to develop novel oral drug delivery systems based on microspheres capable of increased bioadhesion with mucus. The bioadhesive phenomenon has been classically attributed to the use of polymers containing high concentrations of carboxyl groups (believed to form hydrogen bonds with mucus) and the presence of flexible polymer chains (thought to interpenetrate biological structures). We found that hydrophobic bioerodible thermoplastics exhibit very high bioadhesive -properties despite the lack of flexible polymer chains. The strongest example of thermoplastic bioadhesion occurred with polyanhydride copolymers. We believe the mechanism for adhesion is the high density of carboxylic groups exposed during degradation, and that other hydrophobic polymers with high concentrations of surface hydrophilic moieties will exhibit strong bioadhesive measurements. It is our hypothesis that performance of these novel drug delivery systems can be predicted by in vitro measurements of bioadhesive forces using four different methods: everted sac biaossay and measurements from CAHN, EMFT and contact angle studies. The four methods can be utilized to predict the performance of polymer systems in both rats and in larger animals (pigs). The end goal is to overcome the trans-species barrier in order to potentiate our drug delivery systems for use in humans. The significance of the proposed research is that it seeks to apply fundamental findings, derived from basic research into microsphere bioadhesion, to the development of new drug delivery systems and apply this to in vivo experiments in different species. The end goal is to move these novel drug delivery systems from research to clinical applications for treatment of diseases.

我们建议开发基于微球的新型口服药物递送系统，该微球能够增加与粘液的生物粘附性。生物黏附现象被经典地归因于使用含有高浓度羧基的聚合物(据信与粘液形成氢键)和柔性聚合物链的存在(被认为可穿透生物结构)。我们发现，尽管缺乏柔性的高分子链，但疏水性生物可腐蚀性热塑性塑料表现出非常高的生物粘附性。热塑性生物粘附性最强的例子是聚酸酐共聚物。我们认为，粘附性的机制是降解过程中暴露出高密度的羧基，而其他表面亲水部分浓度较高的疏水聚合物将显示出很强的生物粘附性。我们的假设是，这些新型给药系统的性能可以通过使用四种不同的方法进行生物粘附力的体外测量来预测：外翻囊生物显微镜以及Cahn、EMFT和接触角研究的测量。这四种方法可以用来预测聚合物系统在大鼠和较大动物(猪)中的性能。最终目标是克服跨物种障碍，以加强我们的药物输送系统，用于人类。这项拟议研究的意义在于，它寻求将微球生物黏附基础研究得出的基本结果应用于开发新的药物输送系统，并将其应用于不同物种的体内实验。最终目标是将这些新型药物传递系统从研究转移到临床应用，用于治疗疾病。

项目成果

A microtensiometer for the analysis of bioadhesive microspheres.

用于分析生物粘附微球的微张力计。

• 发表时间: 1995
• 期刊: Biomedical instrumentation & technology
• 作者: Chickering3rd,DE;Harris,WP;Mathiowitz,E
• 通讯作者: Mathiowitz,E

Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.

通过减小粒径和添加粘合剂聚（富马酸-癸二酸）酐来提高双香豆素的相对生物利用度。

• DOI: 10.1023/a:1024474609667
• 发表时间: 2003
• 期刊: Pharmaceutical research
• 影响因子: 3.7
• 作者: Thanos,CG;Liu,Z;Reineke,J;Edwards,E;Mathiowitz,E
• 通讯作者: Mathiowitz,E

Evaluation of anhydride oligomers within polymer microsphere blends and their impact on bioadhesion and drug delivery in vitro.

评估聚合物微球共混物中的酸酐低聚物及其对体外生物粘附和药物递送的影响。

• DOI: 10.1016/s0142-9612(03)00219-9
• 发表时间: 2003
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Santos,CA;Freedman,BD;Ghosn,S;Jacob,JS;Scarpulla,M;Mathiowitz,E
• 通讯作者: Mathiowitz,E

Correlation of two bioadhesion assays: the everted sac technique and the CAHN microbalance.

两种生物粘附测定的相关性：外翻囊技术和 CAHN 微量天平。

• DOI: 10.1016/s0168-3659(99)00109-1
• 发表时间: 1999
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Santos,CA;Jacob,JS;Hertzog,BA;Freedman,BD;Press,DL;Harnpicharnchai,P;Mathiowitz,E
• 通讯作者: Mathiowitz,E