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 erythrocytes was evaluated. QN-loaded nanocapsules presented an adequate particle size (176 nm), narrow particle 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.