Biocompatibility and <em>In Vivo</em> Tolerability of a New Class of Photoresponsive Alkoxylphenacyl-Based Polycarbonates

Potential toxicities of chromophoric or polymeric units of most photoresponsive delivery systems have impacted clinical relevance. Herein, we evaluated the biocompatibility and tolerability of alkoxylphenacyl-based polycarbonates (APPs) as a new class of photoresponsive polymers. The polymers were applied as homopolymer or copolymers of polyethylene glycol (10%, w/w) or polycaprolactone (10%, w/w). APP polymers were comparable to poly(lactic-co-glycolic acid) (PLGA) based on cytotoxicity, macrophage activation, and blood compatibility. Data from biodistribution studies in BALB/c mice showed preferential accumulation in kidney and liver. Meanwhile, potential application of APP polymers as immediate or sustained (implants) drug delivery systems indicated that liver and kidney functions were not distorted. Also, plasma levels of tumor necrosis factor-alpha and interleukin-6 were comparable to PLGA-treated mice (p > 0.05). A histological analysis of liver and kidney sections showed no detectable damage for APP polymers. The overall data strongly supported potential consideration of APP polymers as photoresponsive delivery systems especially as implantable or tissue-mimicking photopatterned biomaterials.

大多数光响应递送系统的发色团或聚合物单元的潜在毒性影响了其临床相关性。在此，我们评估了基于烷氧基苯甲酰基的聚碳酸酯（APPs）作为一类新型光响应聚合物的生物相容性和耐受性。这些聚合物作为均聚物或聚乙二醇（10%，w/w）或聚己内酯（10%，w/w）的共聚物使用。基于细胞毒性、巨噬细胞激活和血液相容性，APP聚合物与聚乳酸 - 羟基乙酸共聚物（PLGA）相当。在BALB/c小鼠体内生物分布研究的数据显示，其在肾脏和肝脏中优先聚集。同时，APP聚合物作为即时或持续（植入物）药物递送系统的潜在应用表明，肝脏和肾脏功能未受损害。此外，肿瘤坏死因子 -α和白细胞介素 - 6的血浆水平与PLGA处理的小鼠相当（p>0.05）。对肝脏和肾脏切片的组织学分析表明，APP聚合物未造成可检测到的损伤。总体数据有力地支持了将APP聚合物作为光响应递送系统的潜在考虑，特别是作为可植入或模拟组织的光图案化生物材料。