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局部药物递送系统:负载地塞米松的聚氨酯植入物抑制小鼠海绵模型中的炎症性血管生成。

Local drug delivery system: inhibition of inflammatory angiogenesis in a murine sponge model by dexamethasone-loaded polyurethane implants.

机构信息

Center of Research in Biological Science, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil.

出版信息

J Pharm Sci. 2011 Jul;100(7):2886-95. doi: 10.1002/jps.22497. Epub 2011 Jan 31.

Abstract

Implants are defined as controlled sustained release delivery systems of therapeutic agents incorporated or dispersed into a polymeric carrier. These systems can be implanted in specific organs and delivered by the therapeutic agents at the target site to treat various pathological processes. In the present study, the effects of dexamethasone-loaded polyurethane implants [PU ACT (dexamethasone acetate) implants] on inflammatory angiogenesis in a murine sponge model were investigated. PU ACT implants were inserted into nonbiocompatible sponges, used as a framework for fibrovascular tissue growth, and implanted into subcutaneous tissue located on the back of mice. After 7 days of implantation, the implant system was collected and processed for the assessment of hemoglobin (Hb; vascular index), myeloperoxidase (MPO), and N-acetyl-β-D-glucosaminidase (NAG; inflammatory enzymes activities) and collagen content. ACT released from the polymeric implants provided a significant decrease in the neovascularization in the sponge (Hb content). PU ACT implants provided no effects on neutrophil infiltration (MPO activity) but macrophage recruitment was affected by the glucocorticoid delivered by implants (NAG activity). ACT released from implants was able to reduce the collagen deposition. The qualitative histological findings corroborated with the measured biochemical parameters. These local drug delivery systems derived from polyurethane efficiently modulated the key components of inflammation, angiogenesis, and fibrosis induced by sponge discs in an experimental animal model.

摘要

植入物被定义为将治疗剂掺入或分散到聚合物载体中的受控持续释放递送系统。这些系统可以植入特定的器官,并在靶部位释放治疗剂,以治疗各种病理过程。在本研究中,研究了载有地塞米松的聚氨酯植入物[PU ACT(地塞米松醋酸酯)植入物]对小鼠海绵模型中炎症性血管生成的影响。PU ACT 植入物被插入非生物相容性海绵中,用作纤维血管组织生长的框架,并植入位于小鼠背部的皮下组织中。植入 7 天后,收集植入系统并进行处理,以评估血红蛋白(Hb;血管指数)、髓过氧化物酶(MPO)和 N-乙酰-β-D-氨基葡萄糖苷酶(NAG;炎症酶活性)和胶原含量。聚合物植入物释放的 ACT 显著减少了海绵中的新生血管化(Hb 含量)。PU ACT 植入物对中性粒细胞浸润(MPO 活性)没有影响,但植入物释放的糖皮质激素影响了巨噬细胞的募集(NAG 活性)。植入物释放的 ACT 能够减少胶原沉积。定性组织学发现与测量的生化参数相符。这些源自聚氨酯的局部药物递送系统有效地调节了实验动物模型中由海绵盘诱导的炎症、血管生成和纤维化的关键成分。

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