Effects of Surface Characteristics of Polymeric Nanocapsules on the Pharmacokinetics and Efficacy of Antimalarial Quinine

Luana Roberta Michels,1 Tamara Ramos Maciel,1 Kelly Ayumi Nakama,1 Flavia Elizabete Guerra Teixeira,1 Felipe Barbosa de Carvalho,1 André Gundel,2 Bibiana Verlindo de Araujo,3 Sandra Elisa Haas1 1Pharmaceutical Sciences Post Graduate Program, Pharmacy Course, Federal University of Pampa, UNIPAMPA, Uruguaiana, RS, Brazil; 2Campus Bagé, Federal University of Pampa, UNIPAMPA, Bagé, RS 1650, Brazil; 3Pharmaceutical Sciences Post Graduate Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 2752, BrazilCorrespondence: Sandra Elisa HaasCurso de Farmácia, Universidade Federal do Pampa, UNIPAMPA, Uruguaiana, BrazilTel +55 55 39110200Email sandrahaas@unipampa.edu.brIntroduction: The surface charge of nanoparticles, such as nanospheres (NS) and nanocapsules (NC), has been studied with the purpose of improving the in vivo performance of drugs. The aim of this study was to develop, characterize, and evaluate the in vitro antimalarial efficacy of NCP80 and NSP80 (polysorbate coated) or NCEUD and NSEUD (prepared with Eudragit RS 100) loading quinine (QN).Methods: Formulations were prepared by the nanoprecipitation method, followed by wide physicochemical characterization. Antimalarial activity in Plasmodium berghei-infected mice and populational pharmacokinetics (PopPK) in rats were evaluated.Results: The formulations showed a nanometric range (between 138 ± 3.8 to 201 ± 23.0 nm), zeta potential (mV) of −33.1 ± 0.7 (NCP80), −30.5 ± 1 (UNCP80), −25.5 ± 1 (NSP80), −20 ± 0.3 (UNSP80), 4.61 ± 1 (NCEUD), 14.1 ± 0.9 (UNCEUD), 2.86 ± 0.3 (NSEUD) and 2.84 ± 0.6 (UNSEUD), content close to 100%, and good QN protection against UVA light. There was a twofold increase in the penetration of QN into infected erythrocytes with NC compared to that with NS. There was a sign