Polycaprolactone-Vitamin E TPGS Micellar Formulation for Oral Delivery of Paclitaxel

• Published in: Polymers Vol. 16; no. 15; p. 2232
• Main Authors: Binkhathlan, Ziyad, Ali, Raisuddin, Yusuf, Osman, Alomrani, Abdullah H, Badran, Mohamed M, Alshememry, Abdullah K, Alshamsan, Aws, Alqahtani, Faleh, Qamar, Wajhul, Attwa, Mohamed W
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-08-2024
• Subjects: Bioavailability; block copolymer; Cancer; Chemotherapy; Copolymers; Fluorescent indicators; intestinal permeability; Laboratories; Micelles; oral; Oral administration; Paclitaxel; Permeability; Pharmaceutical industry; Polycaprolactone; polycaprolactone–vitamin E TPGS; Polydispersity; Polyethylene glycol; polymeric micelles; Polymerization; Rhodamine; Ring opening polymerization; Solvents; Tocopherol; Vitamin E; Saudi Arabia; Canada; United Kingdom > UK; United States > US; China; block copolymer; paclitaxel; intestinal permeability; polymeric micelles; pharmacokinetics; oral; polycaprolactone–vitamin E TPGS
• ISSN: 2073-4360; 2073-4360
• DOI: 10.3390/polym16152232

This study aimed to investigate the potential of polycaprolactone-vitamin E TPGS (PCL-TPGS) micelles as a delivery system for oral administration of paclitaxel (PTX). The PCL-TPGS copolymer was synthesized using ring opening polymerization, and PTX-loaded PCL-TPGS micelles (PTX micelles) were prepared via a co-solvent evaporation method. Characterization of these micelles included measurements of size, polydispersity, and encapsulation efficiency. The cellular uptake of PTX micelles was evaluated in
cells using rhodamine 123 (Rh123) as a fluorescent probe. Moreover, an everted rat sac study was conducted to evaluate the ex vivo permeability of PTX micelles. Additionally, a comparative pharmacokinetic study of PTX micelles versus the marketed formulation, Ebetaxel
(a Taxol generic), was performed after a single oral administration to rats. The results demonstrated that the micellar formulation significantly improved PTX solubility (nearly 1 mg/mL). The in vitro stability and release of PTX micelles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) demonstrated that PTX micelles remained stable for up to 24 h and significantly slowed the release of PTX in both media compared to Ebetaxel
. The in vitro cellular uptake, ex vivo intestinal permeability, and in vivo pharmacokinetic profile demonstrated that PTX micelles enhanced the permeability and facilitated a rapid absorption of the drug. Conclusively, the PCL
-TPGS
micelles exhibit potential as an effective oral delivery system for PTX.