Drug Solubilization and Delivery from Cyclodextrin-Pluronic Aggregates

Abstract

Colloidal systems based on Pluronic® F127 (PF127) and hydroxypropyl-beta-cyclodextrin (HPβCD) have been characterized with a view to their potential use as delivery systems of hydrophobic drugs. Complexation of PF127 and HPβCD was evaluated by surface tension measurements, 1H-NMR spectroscopy and transmission electron microscopy. The critical micellar concentration, CMC, at 25 °C of PF127 (0.39 mM in pH 5.8 and 7.4 phosphate buffers, and 0.59 mM in pH 4.5 acetic/acetate and lactic/lactate buffers) was shifted to higher values by the addition of 38.17 mM HP CD (CMCapp = 1.18 mM). This is related to the threading of HPβCD onto the PF127 chains, as confirmed by 1H NMR experiments. HPβCD at this concentration notably raised the sol–gel transition temperature; the minimum PF127 concentration required for providing gelling systems in physiological environments being 13.4 mM. Both HPβCD and PF127 by themselves are able to notably increase the solubility of sertaconazole (SN). At HPβCD concentrations below 80 mM, an additive effect of both components on SN solubility was observed. At greater HPβCD concentrations, a non-additive increase occurred, which is related to the complexation of some PF127 unimers with HPβCD molecules, decreasing the total number of micelles and HPβCD cavities available for interacting with SN. The 13.4 mM PF127/38.17 mM HPβCD system, able to increase up to 100 times the SN solubility in pH5.8 phosphate buffer, showed temperature-dependent drug diffusion coefficients, able to control the release for one week at 37 °C.