Details

Autor(en) / Beteiligte

• Seo, Youn Gee
• Kim, Dong-Wuk
• Yeo, Woo Hyun
• Ramasamy, Thiruganesh
• Oh, Yu-Kyoung
• Park, Young-Joon
• Kim, Jung-Ae
• Oh, Dong Hoon
• Ku, Sae Kwang
• Kim, Jin Ki
• Yong, Chul Soon
• Kim, Jong Oh
• Choi, Han-Gon

Titel

Docetaxel-Loaded Thermosensitive and Bioadhesive Nanomicelles as a Rectal Drug Delivery System for Enhanced Chemotherapeutic Effect

Ist Teil von

• Pharmaceutical research, 2013-07, Vol.30 (7), p.1860-1870

Ort / Verlag

Boston: Springer US

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• ABSTRACT Purpose To investigate the potential of thermosensitive and biadhesive nanomicelles in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect. Method DCT-loaded nanomicelles were prepared by emulsufication and characterized in terms of physico-chemical and visco-elastic parameters. The optimzed formulation was evaluated for in vivo localization, pharmacokinetic and anti-tumor efficacy. Results The hydrodynamic size of DCT-loaded nanomicelles was approximately 13 nm and the nanomicelles exhibited a sufficient gelation strength (9250 mPa·s) and bioadhesive force (2100 dyn/cm 2 ) to be retained in the upper part of rectum. We observed a high rectal bioavailability of 29% DCT compared to that following oral administration in rats, as it successfully evaded the multidrug efflux transporters and hepatic first-pass metabolism. Plasma concentration around ∼50 ng/mL was maintained throughout the study period (12 h) while Taxotere® attained subtherapeutic range within 4 h of drug administration. Results also revealed that the rectally administered DCT-loaded nanomicelles exhibited a significant anti-tumor effect (200 mm 3 ) with a reduced toxicity profile when compared to orally administered DCT (950 mm 3 ). Furthermore, histological study showed that the rectal mucosa was completely intact with no signs of irritation upon treatment with DCT-loaded nanomicelles. Conclusions Taken together, our novel thermosensitive and biadhesive nanomicelles demonstrated the ability to improve the bioavailability and chemotherapeutic potential of DCT in vivo . To the best of our knowledge, this is the first report describing the rectal delivery of DCT-loaded nanomicelles.