Irinotecan-encapsulated double-reverse thermosensitive nanocarrier system for rectal administration

作者：Fakhar ud Din, Ju Yeon Choi, Dong Wuk Kim, Omer Mustapha, Dong Shik Kim, Raj Kumar Thapa, Sae‐Kwang Ku, Yu Seok Youn, Kyung Taek Oh, Chul Soon Yong, Jong Oh Kim, Han‐Gon Choi · 发表于：Drug Delivery · 年份：2017 · DOI：10.1080/10717544.2016.1272651 · 被引用次数：110 · 研究领域：Nanoparticle-Based Drug Delivery、Advanced Drug Delivery Systems、Advancements in Transdermal Drug Delivery

Intravenously administered for the treatment of rectum cancer, irinotecan produces severe side effects due to very high plasma concentrations. A novel irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration was developed as an alternative. The DRTN was fabricated by dispersing the thermosensitive irinotecan-encapsulated solid lipid nanoparticles (SLN) in the thermosensitive poloxamer solution. Its gel properties, pharmacokinetics, morphology, anticancer activity and immunohistopathology were assessed after its rectal administration to rats and tumor-bearing mice. In the DRTN, the solid form of the SLN and the liquid form of the poloxamer solution persisted at 25 °C; the former melted to liquid, and the latter altered to gel at 36.5 °C. The DRTN was easily administered to the anus, gelling rapidly and strongly after rectal administration. Compared to the conventional hydrogel and intravenously administered solution, it retarded dissolution and initial plasma concentration. The DRTN gave sustained release and nearly constant plasma concentrations of irinotecan at 1-3 h in rats, resulting in improved anticancer activity. It induced no damage to the rat rectum and no body weight loss in tumor-bearing mice. Thus, this irinotecan-encapsulated DRTN associated with a reduced burst effect, lack of toxicity and excellent antitumor efficacy would be strongly recommended as a rectal pharmaceutical product alternative to commercial intrav...