Nanoencapsulation increases quinine antimalarial efficacy against Plasmodium berghei in vivo

The aims of this work were to develop quinine (QN)-loaded nanocapsules, to evaluate their efficacy in vivo and to determine their pharmacokinetics and erythrocyte partition coefficient. Plasmodium berghei-infected Wistar rats were used to evaluate the efficacy of QN-loaded nanocapsules using different dosing regimens. Pharmacokinetics was evaluated after intravenous administration of free or nanoencapsulated QN (25 mg/kg) to infected rats. The QN partition coefficient into P. berghei-infected erythrocyteswas evaluated. QN-loaded nanocapsules presented an adequate particle size (176 nm), narrowparticle distribution (0.19), negative zeta potential (-18 mV) and high drug content and encapsulation efficiency. Intravenous administration of QN-loaded nanocapsules at 75 mg/kg/day to infected rats resulted in 100% survival, representing an almost 30% reduction compared with the free QN effective dose (105 mg/kg/day). The pharmacokinetic parameters of nanoencapsulated QN were not significantly different from those determined for free drug (alpha = 0.05). The QN partition coefficient into infected erythrocytes doubled (6.25 +/- 0.25) when the drug was nanoencapsulated compared with the free drug (3.03 +/- 0.07). Therefore, nanoencapsulation increased the interaction between QN and the erythrocyte and this mechanism is responsible for the drug's increased efficacy when nanoencapsulated. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.,