3-羥基丁酸酯與3-羥基戊酸酯共聚物微粒製備與藥物制放

Preparation and Drug Delivery of Microspheres from 3-Hydroxybutyrate and 3-Hydroxyvalerate Copolymers

盧正慧(Jen-Hui Lu)

指導教授 ： 王賢達

國立臺北科技大學/工程學院/有機高分子研究所/碩士(2006年)

摘要

本研究是以雙乳化(W1/O/W2)溶劑揮發法製備含小牛血清蛋白(BSA)之3-羥基丁酸酯與3-羥基戊酸酯共聚物(PHBV)微粒。製備參數包括乳化溫度、攪拌速度、BSA濃度、PHBV濃度、界面活性劑種類和界面活性劑濃度曾被改變，以了解會對微粒產率、BSA含量、粒徑、表面形態和藥物釋放的影響。
乳化溫度和攪拌速度的改變並未造成微粒產率、BSA含量和粒徑較大的變動。BSA濃度的降低和PHBV濃度的增加，造成BSA含量和微粒產率的提升。PHBV的濃度增加也增大了粒徑。聚乙烯醇(PVA)界面活性劑濃度的增加降低了粒徑和BSA含量，但增加了粒子表面孔洞性。失水山梨醇單油酸酯(Span 80)界面活性劑濃度的增加，降低了粒徑和BSA含量，但增加了粒子表面平滑性。使用Pluronic F-68界面活性劑降低了BSA含量。
含BSA微粒的制放曲線大致開始以較大的釋放，隨後就是微緩的釋放或是趨近於零的釋放。微粒製備使用低濃度的PHBV、相對較高濃度的PVA或Pluronic F-68會有較高的BSA起始制放；使用Span 80界面活性劑製備的微粒，其BSA起始制放較小。使用低濃度PHBV製備微粒具有較多的孔洞，因而造成隨後BSA微緩釋放。

關鍵字

3-羥基丁酸酯與3-羥基戊酸酯共聚物 ； 微粒 ； 雙乳化溶劑揮發法 ； 藥物制放

並列摘要

Microspheres of 3-hydroxbutyrate and 3-hydroxyvalerate copolymers (PHBV) containing bovine serum albumin (BSA) have been prepared using double emulsion (W1/O/W2) solvent evaporation method in this research. Parameters including temperature of emulsification, stirring velocity, concentration of BSA or PHBV or emulsifier, and species of surfactants have been varied during microsphere preparation in order to investigate the influence on particle yield, BSA incorporation efficiency, microsphere diameter, surface morphology and drug delivery.
Changes in temperature of emulsification and stirring velocity during preparation would not cause much influence on BSA incorporation efficiency and average microsphere diameter in this study. Decrease of BSA concentration and increase of PHBV concentration in preparation procedures elevated BSA incorporation of microspheres and particle yield. In addition, increase in PHBV concentration in preparation method enlarged average particle diameter. With increase in concentration of polyvinyl alcohol (PVA) surfactant for microsphere preparation, average particle diameter and BSA incorporation efficiency decreased and surface porosity of microspheres increased. With the use of sorbitan monooleate (Span 80) surfactant in preparation, decrease in average microsphere diameter or BSA incorporation and increase in surface smoothness of particles has been found after characterization. The use of Pluronic F-68 (PF-68) surfactant also lowered BSA incorporation efficiency of prepared microspheres.
The cumulative BSA release curve for microspheres basically started with a burst effect of release and followed with a slow release or approaching zero release. The burst effect of BSA release of microspheres would be higher for application of low concentration of PHBV or relatively high concentration of PVA or PF-68 during preparation and lower for use of Span 80. The slow release following initially sudden BSA release for microsphere prepared with low concentration of PHBV was believed to be due to higher porosity of particles.

並列關鍵字

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) ； Microsphere ； Double Emulsion Solvent Evaporation Method ； Drug Delivery

參考文獻

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