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

Area of Science:

• Pharmaceutical Sciences
• Biotechnology
• Oncology

Background:

• Intravenous irinotecan for rectal cancer causes severe side effects due to high plasma concentrations.
• A new rectal drug delivery system is needed to improve treatment efficacy and reduce toxicity.

Purpose of the Study:

• To develop and evaluate an irinotecan-encapsulated double reverse thermosensitive nanocarrier system (DRTN) for rectal administration.
• To assess the DRTN's physicochemical properties, pharmacokinetics, anticancer activity, and safety profile.

Main Methods:

• Fabrication of DRTN by dispersing thermosensitive irinotecan-loaded solid lipid nanoparticles (SLN) in a thermosensitive poloxamer solution.
• Evaluation of gelation properties, rectal administration in rats and tumor-bearing mice, pharmacokinetic studies, and assessment of anticancer efficacy and immunohistopathology.

Main Results:

• The DRTN demonstrated thermosensitive gelation at body temperature after rectal administration.
• Compared to conventional methods, DRTN showed sustained irinotecan release, reduced initial plasma concentration, and prolonged therapeutic levels.
• Improved anticancer activity was observed with no rectal damage or systemic toxicity in animal models.

Conclusions:

• The irinotecan-encapsulated DRTN is a promising rectal pharmaceutical product for treating rectal and colon cancer.
• This novel nanocarrier system offers reduced toxicity and enhanced antitumor efficacy compared to intravenous irinotecan.
• DRTN represents a viable alternative to conventional intravenous chemotherapy for rectal cancer treatment.