l-Carnitine conjugated chitosan-stearic acid polymeric micelles for improving the oral bioavailability of paclitaxel

Autor: Hailan Mo, Wei Zhang, Tan Yang, Wei Wu, Jianfang Feng, Lanzhen Huang, Qian Zhang
Rok vydání: 2020
Předmět:
Male
Paclitaxel
Administration
Oral
Biological Availability
Pharmaceutical Science
RM1-950
macromolecular substances
02 engineering and technology
Conjugated system
030226 pharmacology & pharmacy
Micelle
Rats
Sprague-Dawley
Chitosan
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Carnitine
medicine
Animals
Humans
Particle Size
Solute Carrier Family 22 Member 5
Micelles
Drug Carriers
Polymeric micelles
technology
industry
and agriculture
General Medicine
021001 nanoscience & nanotechnology
l-carnitine
Antineoplastic Agents
Phytogenic
Bioavailability
Drug Liberation
oral bioavailability
Intestinal Absorption
chemistry
Female
lipids (amino acids
peptides
and proteins)
Therapeutics. Pharmacology
Stearic acid
Caco-2 Cells
0210 nano-technology
Stearic Acids
Research Article
medicine.drug
Nuclear chemistry
Zdroj: Drug Delivery
Drug Delivery, Vol 27, Iss 1, Pp 575-584 (2020)
ISSN: 1521-0464
1071-7544
Popis: A delivery system based on l-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 μg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.
Databáze: OpenAIRE
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