POLY(ETHYLENE OXIDE)-B-POLY(PROPYLENE OXIDE) POLYMERIC MICELLES WITH AN INORGANIC CORONA CROSSLINKING

Introduction. Polymeric micelles (PMs) can increase aqueous solubility of poorly water-soluble drugs. Two main drawbacks of PMs are disassembly under dilution in body fluids and poor control of the cargo release rate. Crosslinking the corona of PMs is a valuable approach to stabilize the micelles. In this work, poly(ethylene oxide)-b-poly(propylene oxide) copolymers (PEO-PPOs) were modified with 3-isocyanatopropyl triethoxysilane (IPTS) (1) and the corona crosslinked employing the sol-gel chemistry coupled to the spray drying technology.

Methods. The critical micellar concentration (CMC) and the micellar size and size distribution were measured by DLS and the micellar concentration by NTA. The morphology was visualized by SEM and the encapsulation and release in vitro of the highly hydrophobic antiretroviral tipranavir studied for the first time by UV.

Results. Crosslinking by condensation and freeze-drying brought to a massive crosslinking. More controlled crosslinking was achieved by condensation by spray-drying. Three populations of micelles of 7, 45-55 and 450-550nm were measured in pristine and modified polymers at room temperature and one population of 20-30nm at 37°C. After crosslinking one main population of 150 nm, at room temperature and 85 nm at 37°C was obtained. Encapsulation in pristine and modified copolymers increased the aqueous solubility of the model drug by three orders of magnitude. Moreover, crosslinking stabilized the micelles and enabled a more controlled release.

Conclusion. The present work introduces a novel approach to produce physically stable PMs that display a release-controlling membrane on the surface.

References. 1. Sosnik A, Cohn D, Biomaterials 25, 2851-2858 (2004).