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

Drug Delivery

Sae Kwang Ku¹  Dong Wuk Kim²  Han-Gon Choi²  Omer Mustapha²  Dong Shik Kim²  Fakhar ud Din²  Kyung Taek Oh³  Raj Kumar Thapa⁴  Ju Yeon Choi⁴  Chul Soon Yong⁴  Jong Oh Kim⁴  Yu Seok Youn⁵ 

[1] College of Oriental Medicine, Daegu Haany University;College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University;College of Pharmacy, Chung-Ang University;College of Pharmacy, Yeungnam University;School of Pharmacy, Sungkyunkwan University;

关键词: irinotecan;    double reverse thermosensitive nanocarrier;    rectal administration;    burst effect;    toxicity;    anti-tumor efficacy;   

DOI  :  10.1080/10717544.2016.1272651

来源: DOAJ

【 摘 要 】

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 intravenous injection in the treatment of rectum and colon cancer.

【 授权许可】

Unknown