The Influence of Glass Transition Temperature of PMMA-Based Nanoparticles on the Release Profile of Praziquantel as a Strategy for Controlling Drug Release

Abstract

In the present work, nanoparticles of poly(methyl methacrylate-co-butyl acrylate) (P(MMA-co-BA)) and poly(methyl methacrylate-co-vinyl acetate) (P(MMA-co-VAc)) were synthesized by miniemulsion polymerization with the in situ encapsulation of praziquantel (PZQ) as a hydrophobic drug model. The reactions produced nanoparticles with diameters ranging from 67 ± 0.5 to 130 ± 1.1 nm, with an encapsulation efficiency of at least 99%. The glass transition temperatures (T g 's) of the produced copolymer nanoparticles were successfully reduced from 121.5 to −9.3 °C in the absence of PZQ and from 100.7 to −13.7 °C in the presence of encapsulated PZQ. In vitro release assays carried out at 37 and 50 °C showed that the rate of drug release increased with temperature, reaching maxima of 56 ± 3.7 and 38 ± 2.9% of release in 6 h for copolymers containing 40 wt % BA and 60 wt % VAc. Modeling of the available release data indicated the occurrence of an anomalous release mechanism as the driver for the drug release from the produced nanoparticles. Empirical mathematical modeling confirmed the influence of both the T g and the test temperature on the rate of drug release. Finally, experimental results strongly suggested that PZQ exerts a plasticizer effect in the system, as confirmed by DSC analyses, suggesting the existence of specific interactions between the drug and the polymer matrix. Altogether, these results point out the occurrence of multifactorial effects on release of hydrophobic drugs from nondegradable polymer particles.