title: Docetaxel-loaded thermosensitive and bioadhesive nanomicelles as a rectal drug delivery system for enhanced chemotherapeutic effect.
abstract: OBJECTIVE
  To investigate the potential of thermosensitive and biadhesive nanomicelles in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect.
  
  
  METHODS
  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/cm²) 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 mm³) with a reduced toxicity profile when compared to orally administered DCT (950 mm³). 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.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1 Dae-Dong, Gyongsan 712-749, South Korea.
authors.forename: Youn Gee
authors.initials: YG
authors.lastname: Seo
authors.forename: Dong-Wuk
authors.initials: DW
authors.lastname: Kim
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Yeo
authors.forename: Thiruganesh
authors.initials: T
authors.lastname: Ramasamy
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Park
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Oh
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Jin Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077143:Docetaxel; D016503:Drug Delivery Systems; D005260:Female; D008297:Male; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D043823:Taxoids; D000077143:Docetaxel
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