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.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Sandra Elisa
SE
Haas
Clarissa Cassini
CC
Bettoni
Laura Kausburg
LK
de Oliveira
Sílvia Stanisçuaski
SS
Guterres
Teresa
T
Dalla Costa
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers / Q000008:administration & dosage*; D004912:Erythrocytes / Q000737:chemistry; D007275:Injections, Intravenous; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D010962:Plasmodium berghei / Q000187:drug effects*; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D016896:Treatment Outcome
D000962:Antimalarials; D004337:Drug Carriers; D011803:Quinine