Leong K W, D'Amore P D, Marletta M, Langer R
J Biomed Mater Res. 1986 Jan;20(1):51-64. doi: 10.1002/jbm.820200106.
The biocompatibility of bioerodible polyanhydrides and toxicology of the polymer breakdown products were assessed. Poly-[bis (p-carboxy-phenoxy) propane anhydride] (PCPP), Poly(terephthalic acid anhydride) (PTA), and their copolymers with sebacic acid were tested. The polymers did not provoke inflammatory responses in the corneas of rabbits over a six week implantation period. Subcutaneous implantation studies of PCPP in rats over a six month period showed no evidence of inflammatory cells and only slight tissue encapsulation by layers of fibroblastic cells. The degradation products of the polymers were nonmutagenic, noncytotoxic, and had a low teratogenic potential. The in vitro growth of mammalian cells on the polymers was unaffected as measured by cell morphology and cell growth rate. The chemical reactivity of the polyanhydrides with reactive model drugs, para substituted anilines, was also examined. Amides were formed when the drugs were injection molded with the polyanhydrides at 120 degrees C. However, no reaction was observed using compression molding at room temperature. No reaction occurred between the polymer and the drug during the hydrolytic degradation of the matrix at 37 degrees C.
评估了可生物蚀解的聚酸酐的生物相容性以及聚合物降解产物的毒理学。测试了聚[双（对羧基苯氧基）丙烷酐]（PCPP）、聚（对苯二甲酸酐）（PTA）及其与癸二酸的共聚物。在六周的植入期内，这些聚合物未在兔角膜中引发炎症反应。对大鼠进行的为期六个月的PCPP皮下植入研究表明，没有炎症细胞的迹象，仅见有成纤维细胞层形成的轻微组织包囊。聚合物的降解产物无致突变性、无细胞毒性且致畸潜力低。通过细胞形态和细胞生长速率测定，哺乳动物细胞在聚合物上的体外生长未受影响。还研究了聚酸酐与反应性模型药物对取代苯胺的化学反应性。当药物在120℃与聚酸酐注射成型时形成了酰胺。然而，在室温下进行压缩成型时未观察到反应。在37℃基质的水解降解过程中，聚合物与药物之间未发生反应。
