Luzardo-Álvarez A, Blanco-Méndez J, Varela-Patiño P, Martín Biedma B
a Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
J Biomater Sci Polym Ed. 2011;22(1-3):329-42. doi: 10.1163/092050610X486937.
The difficulty of eliminating Enterococcus faecalis and other bacteria infecting dental root canals makes it desirable to develop formulations capable of sustained release of antibiotics within the canal. With this function in view, in this work we compared the mechanical, drug release and biocompatibility properties of amoxicillin-loaded collagen (CL) and CL complexed with poly[(methyl vinyl ether)-co-(maleic anhydride)] (PVMMA), with or without glutaraldehyde (GTA) or the natural product genipin (GN) as cross-linker. Collagen was not denatured by complexation with PVMMA. Only CL-PVMMA-GN sponges did not disintegrate during 7 days exposure to cell culture medium (un-cross-linked CL disintegrated within 24 h and un-cross-linked CL-PVMMA within 4 days), and CL-PVMMA-GN sponges also exhibited the most appropriate combination of mechanical properties (hardness, modulus of deformability and plasticity). CL-PVMMA-GN sponges absorbed aqueous medium faster than other cross-linked formulations, but their maximum uptake was less; and drug release from CL-PVMMA-GN sponges tended to be faster than from any other, except un-cross-linked CL-PVMMA, maximum release taking about 4 days. No formulation significantly altered the viability of L929 fibroblast-like mouse connective tissue cells, but cells growing on sponges showed signs of non-adherence. It is concluded that genipin-cross-linked CL-PVMMA sponges merit further investigation as antibiotics vehicles and aids to tissue regeneration in the dental root canal.
消除粪肠球菌和其他感染牙根管的细菌存在困难,因此需要开发能够在根管内持续释放抗生素的制剂。鉴于此功能,在本研究中,我们比较了负载阿莫西林的胶原蛋白(CL)以及与聚[(甲基乙烯基醚)-co-(马来酸酐)](PVMMA)复合的CL的机械性能、药物释放性能和生物相容性,其中使用或不使用戊二醛(GTA)或天然产物京尼平(GN)作为交联剂。胶原蛋白与PVMMA复合后不会变性。只有CL-PVMMA-GN海绵在暴露于细胞培养基7天期间不会崩解(未交联的CL在24小时内崩解,未交联的CL-PVMMA在4天内崩解),并且CL-PVMMA-GN海绵还表现出最合适的机械性能组合(硬度、变形模量和可塑性)。CL-PVMMA-GN海绵比其他交联制剂更快地吸收水性介质,但其最大吸收量较少;并且CL-PVMMA-GN海绵的药物释放往往比任何其他制剂都快,除了未交联的CL-PVMMA,最大释放时间约为4天。没有制剂显著改变L929成纤维细胞样小鼠结缔组织细胞的活力,但在海绵上生长的细胞显示出不粘附的迹象。得出的结论是,京尼平交联的CL-PVMMA海绵作为抗生素载体和牙根管组织再生辅助剂值得进一步研究。