Poly(2-Methyl-2-Oxazoline)/Poly(2-Phenyl-2-Oxazine) Copolymers for Oral Drug Delivery: Effect of Copolymer Architecture
Year: 2025
Type: article
Abstract: Polymeric micelles formed from amphiphilic copolymers offer a promising approach to enhancing the aqueous solubility of hydrophobic drugs, thereby potentially improving their bioavailability. The microstructure of such copolymers can significantly affect their physicochemical and self-assembly properties. As a result, they can differently perform as drug carriers in vivo. In the present work, aqueous solutions of the triblock, diblock and statistical copolymers comprised of hydrophilic poly(2-methyl-2-oxazoline) (pMeOx) and hydrophobic poly(2-phenyl-2-oxazine) (pPheOzi) were comparatively studied for their colloidal properties and efficiency in solubilizing a poor water-soluble drug indomethacin (IND). A kinetic study confirmed the gradient architecture of the statistical pMeOx/pPheOzi copolymer. All copolymers effectively encapsulated IND in aqueous media, achieving loading capacities above 29%. Notably, the more easily synthesized gradient copolymer demonstrated drug solubilization performance only 1.5 times lower than that of the block counterparts, still showing sufficient potential as a viable alternative. Self-assembly studies indicated that differences in drug loadings for different copolymer architectures correlate with variations in the colloidal characteristics of the respective solutions. Finally, the aggregation behavior of (loaded) copolymer micelles was studied in the simulated intestinal fluid (FeSSIF). Exhibiting minimal interference with FeSSIF constituents, regardless of architecture, the pMeOx/pPheOzi copolymers were shown to significantly enhance IND solubility in the biorelevant media, presumably due to the drug interaction with taurocholate. Overall, the present study helps elucidate the influence of monomer arrangement in the amphiphilic pMeOx/pPheOzi copolymers on their properties as solubility enhancers for IND and contributes to improving the predictability of pMeOx/pPheOzi-based IND formulations for oral drug delivery.
Source: Työväentutkimus Vuosikirja
Author: Simagina, Liliia
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7198792294