Einmahl Suzanne, Ponsart Stéphanie, Bejjani Riad A, D'Hermies François, Savoldelli Michelle, Heller Jorge, Tabatabay Cyrus, Gurny Robert, Behar-Cohen Francine
School of Pharmacy, University of Geneva, 30 quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
J Biomed Mater Res A. 2003 Oct 1;67(1):44-53. doi: 10.1002/jbm.a.10597.
The biocompatibility of autocatalyzed poly(ortho ester) (POE(70)LA(30)), a viscous, hydrophobic, bioerodible polymer, was investigated. POE(70)LA(30) was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE(70)LA(30) bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE(70)LA(30) biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE(70)LA(30) were reproducible and well tolerated. POE(70)LA(30) triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE(70)LA(30) appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance.
对自催化聚原酸酯(POE(70)LA(30))——一种粘性、疏水性、可生物降解的聚合物——的生物相容性进行了研究。合成了POE(70)LA(30),通过γ射线辐照进行灭菌,并通过结膜下、前房内、玻璃体内和脉络膜上腔途径以适当体积注入兔眼。术后定期进行6个月的临床检查,并进行组织病理学分析以确认组织生物相容性。结膜下注射后,聚合物耐受性良好,在结膜下间隙持续存在约5周。在前房内注射的情况下,聚合物生物相容性良好;注射后POE(70)LA(30)气泡在前房内仍可存在长达6个月。除了局部Descemet膜增厚外,未检测到重大组织病理学异常。玻璃体内给药后,POE(70)LA(30)生物相容性极佳,在观察期内未检测到炎症反应。聚合物在大约3个月内降解。脉络膜上腔注射POE(70)LA(30)具有可重复性且耐受性良好。临床观察发现POE(70)LA(30)引起视网膜和脉络膜轻微升高。聚合物在脉络膜上腔中可检测到约6个月。组织学检查未发现炎症反应和重大视网膜异常。总之,POE(70)LA(30)似乎是一种有前景的眼内应用生物材料,有可能在较长时间内提供持续的药物递送,且耐受性良好。