Chitosan-phospholipid blend for sustained and localized delivery of docetaxel to the peritoneal cavity.
作者： Payam Zahedi , Raquel De Souza , Micheline Piquette-Miller , Christine Allen
DOI: 10.1016/J.IJPHARM.2009.05.003
关键词: Phospholipid 、 Dosage form 、 Chitosan 、 Peritoneal cavity 、 Drug carrier 、 Magic bullet 、 Toxicity 、 In vivo 、 Chemistry 、 Pharmacology
摘要: Localized and sustained delivery of chemotherapeutics presents a "magic bullet" effect by providing high drug concentrations at the target site, extended exposure reduced systemic toxicity. In present study, an injectable chitosan-phospholipid (PoLi(gel)) blend is put forth as strategy to achieve localized docetaxel (DTX) following intraperitoneal (IP) administration. The stability was confirmed in vitro, turbidity measurements attributed specific molecular interactions organization materials within blend, evidenced FTIR analysis confocal laser scanning microscopy, respectively. chitosan phospholipid were found colocalize regions surrounding mean object area 11.2mum(2) with colocalization coefficients 43% 46% for phospholipid, PoLi(gel) afforded release seen both vitro (2.4+/-0.7% DTX per day) vivo (4.4+/-0.7% day). Constant observed over 2-week period plasma relevant peritoneal tissues, no signs toxicity or inflammation, IP administration healthy CD-1 mice. At doses 28.8 19.2mg/kg, showed significant tumor inhibition 87.3+/-9.3% 74.1+/-25.9%, respectively, murine xenograft model human ovarian adenocarcinoma. This system has shown excellent potential treatment cancers, such ovarian, that reside cavity.
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