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

Title
Docetaxel-Loaded Thermosensitive and Bioadhesive Nanomicelles as a Rectal Drug Delivery System for Enhanced Chemotherapeutic Effect
Author(s)
용철순서윤기김동욱[김동욱]여우현티르거네쉬라마사미오유경[오유경]박영준[박영준]김정애오동훈구세광[구세광]김진기[김진기]최한곤[최한곤]김종오
Keywords
IN-VITRO EVALUATION; LIQUID SUPPOSITORY; ORAL BIOAVAILABILITY; CANCER-THERAPY; RATS; NANOPARTICLES; POLOXAMER; MICELLES; BIODISTRIBUTION; ACID
Issue Date
201307
Publisher
SPRINGER/PLENUM PUBLISHERS
Citation
PHARMACEUTICAL RESEARCH, v.30, no.7, pp.1860 - 1870
Abstract
To investigate the potential of thermosensitive and biadhesive nanomicelles in improving the bioavailability of docetaxel (DCT) and its chemotherapeutic effect. 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. The hydrodynamic size of DCT-loaded nanomicelles was approximately 13 nm and the nanomicelles exhibited a sufficient gelation strength (9250 mPa center dot 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 similar to 50 ng/mL was maintained throughout the study period (12 h) while TaxotereA (R) 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. 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.
URI
http://hdl.handle.net/YU.REPOSITORY/29475http://dx.doi.org/10.1007/s11095-013-1029-0
ISSN
0724-8741
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE