Sintzel M B, Heller J, Ng S Y, Tabatabay C, Schwach-Abdellaoui K, Gurny R
School of Pharmacy, University of Geneva, 30, quai Ernest-Ansermet, CH-1211-Geneva 4, Switzerland.
J Control Release. 1998 Nov 13;55(2-3):213-8. doi: 10.1016/s0168-3659(98)00051-0.
Self-catalyzed poly(ortho esters) are a new variation of linear poly(ortho esters) prepared by the addition of diols to the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5,5]undecane where dimer segments of lactic acid or glycolic acid are built into the polymer backbone. By varying the concentration of these segments, polymer erosion rate can be controlled. The present investigation describes the in vitro drug release characteristics from these new polymers. Because poly(ortho esters) have potential applications for the delivery of antifibroblastic agents for example after glaucoma-filtering surgery, the in vitro release studies were evaluated using 5-fluorouracil as the active compound. It was shown that a mole ratio of 90/10 or 80/20 diol/diol-lactate incorporated into the polymer lead to a release of 5-fluorouracil by an erosion process. Smaller amounts of diol-lactate lead to a concomitant drug release by diffusion and erosion. It was also shown that the release rate depends on the alkyl chain length of the diol in the polymer backbone but it does not depend on the drug loading.
自催化聚原酸酯是线性聚原酸酯的一种新变体，它是通过将二醇添加到双乙烯酮缩醛3,9 - 二亚乙基 - 2,4,8,10 - 四氧杂螺[5,5]十一烷中制备而成，其中乳酸或乙醇酸的二聚体片段被构建到聚合物主链中。通过改变这些片段的浓度，可以控制聚合物的侵蚀速率。本研究描述了这些新型聚合物的体外药物释放特性。由于聚原酸酯在例如青光眼滤过手术后递送抗成纤维细胞药物方面具有潜在应用，因此使用5 - 氟尿嘧啶作为活性化合物对体外释放研究进行了评估。结果表明，掺入聚合物中的二醇/二醇 - 乳酸的摩尔比为90/10或80/20时，5 - 氟尿嘧啶通过侵蚀过程释放。较少量的二醇 - 乳酸会导致药物通过扩散和侵蚀同时释放。还表明，释放速率取决于聚合物主链中二醇的烷基链长度，但不取决于药物负载量。
