PLGA-g-PVP -based nanocapsules for the controlled delivery of antimalarials

Amphiphilic PLGA-g-PVP copolymers with different PLGA and PVP content were recently obtained by the radical polymerization of 1-vinylpyrrolidin-2-one in liquid poly(lactic-co-glycolic acid) (PLGA) (50:50) at 100°C. Saponification of the PLGA portion allowed isolating the PVP side chains and measuring their molecular weight, which turned to be lower than the threshold for glomerular filtration. The orthogonal solvent pair ethyl acetate-methanol gave PLGA-g-PVP fractions with different PLGA and PVP content. Following the same procedure, PLGA/PVP blends gave the two homopolymers. PLGA-g-PVP and PLGA/PLGA-g-PVP blends, but not PLGA/PVP blends, gave long-term stable nanodispersions in water. In this work, PLGA-g-PVP copolymers were employed to obtain novel artemisinin and curcumin formulations. Both drugs are endowed with potential and pitfalls for malaria treatment. Artemisinin is a potent Plasmodium falciparum malaria parasite inhibitor (IC50 = 10-8 - 10-7 M) but with low bioavailability, poor pharmacokinetic properties and high cost. Curcumin inhibits the growth of P. falciparum with a dose dependent trend and IC50 = 5 μM. Despite the absence of secondary effects in humans, the use of curcumin is limited by the low solubility in water, the high chemical instability and photosensitivity, resulting in low bioavailability. To increase bioavailability, artemisinin and curcumin were loaded into nanocapsules consisting of a biocompatible oily core acting as drug solvents, and a PLGA-g-PVP shell. Loaded nanocapsules were characterized in terms of morphology, physico-chemical properties and release tests. In particular, transmission electron microscopy (TEM) showed spherical morphologies and dynamic scattering measurements (DLS) revealed size in the range 50 - 100 nm. The encapsulation efficiency was very high with both drugs and in the case of artemisinin it approached 100%. All formulations showed long-term shelf stability in aqueous solution. In vitro activity tests as P. falciparum inhibitors are currently in progress.