Pluronic block copolymers and Pluronic poly(acrylic acid) microgels in oral delivery of megestrol acetate

Abstract

Several Pluronic-based formulations were studied in-vitro and in a rat model with respect to the release and bioavailability of megestrol acetate (MA) after oral administration. It was demonstrated that an aqueous, micellar formulation comprising a mixture of a hydrophobic (L61) and a hydrophilic (F127) Pluronic copolymer, significantly enhanced the bioavailability of MA administered orally at relatively low doses (1-7 mg kg(-1)). Pluronic-based microgels (spherical gel particles of sub-millimetre size) were introduced as MA vehicles. The microgels comprised a cross-linked network of poly(acrylic acid) onto which the Pluronic chains were covalently attached. Microgels of Pluronic L92 and poly(acrylic acid) fabricated into tablet dosage forms exhibited dramatically lowered MA initial burst release. The MA release was pH-dependent owing to the pH sensitivity of the microgel swelling, with the drug retained by the microgel at pH 1.8 and released slowly at pH 6.8. In the rat model, a significant increase in MA bioavailability was observed when the microgel-formulated MA was administered orally at a high dose of 10 mg kg(-1), owing to the enhanced retention of the microgel. The study of the microgel passage through the gastrointestinal tract demonstrated the microgel retention characteristic of a very high molecular weight polymer and the absence of any systemic absorption of the polymer.

Polymeric micelles: authoritative aspects for drug delivery

“…This shape transition phenomenon was attributed to the increase in number of unimers per micelle. An 5-fold increase in solubility [237] Hydrochlorothiazide Pluronic P103, P123 and F127 Solubility of drug significantly enhanced by increasing copolymer concentration/salt concentration/temperature [238] Ibuprofen N-palmitoyl chitosan pH and temperature-sensitive micelles [38] Indomethacin Cholesteryl-bearing Carboxymethylcellulose pH-sensitive; controlled drug release [239] Megestrol Pluronic F127/L61 Enhanced bioavailability [240] Morphine Pluronic F127 Drug solubilized with prolonged delivery [241] Nimesulide Tetronic T904 Spontaneous micellar solubilization of drug [242] Nystatin Pluronics F68, F98, P105,…”

Thermosensitive Self-Assembling Block Copolymers as Drug Delivery Systems

“…Bromberg and coworkers carried out several and studies regarding the oral administration of doxorubicin, paclitaxel, and megestrol acetate using both cross-linked and uncross-linked Poloxamer-PAA copolymer [130,131].…”

Nanomemulsion of megestrol acetate for improved oral bioavailability and reduced food effect

“…As like other BCS class II drugs, oral bioavailability of MGA is very low and largely affected by food intake (Farinha et al 2000). This issues challenges physicians to optimize the dosage form of MGA to get reliable dose-response (Alakhov et al 2004;Deschamps et al 2009;Cho et al 2010).…”