The Influence of
Glass Transition Temperature
of PMMA-Based Nanoparticles
on the Release Profile of Praziquantel as a Strategy for Controlling
Drug Release
Version 2 2024-01-18, 19:05Version 2 2024-01-18, 19:05
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journal contribution
posted on 2024-01-18, 19:05authored byLys Hamond Regua Mangia, Flávia Yamashita, Camila Guindani, Helen Conceição Ferraz, José Carlos Pinto
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 (Tg’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 Tg 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.