Introduction: 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 significant increase in t_1/2 for all NC evaluated compared to that of Free-QN, due to changes in Vdss. PopPK analysis showed that NCP80 acted as a covariate to Q (intercompartmental clearance) and V2 (volume of distribution in the peripheral compartment). For NCEUD, V1 and Q were modified after QN nanoencapsulation. Regarding in vivo efficacy, NCEUD increased the survival of mice unlike Free-QN. Conclusion: Cationic nanocapsules modified the pharmacology of QN, presenting a potential alternative for malaria treatment.

The unloaded polymeric nanocapsules (NCs) present incredible characteristics as drug carriers. However, the toxicity caused by NCs with different coatings is still a challenge for contemporary toxicology. Allied to this, preclinical studies are performed in males, disregarding possible gender-dependent toxicity. Thus, the aim of present study was to evaluate the influence of different NCs coatings on toxicological and behavioral parameters in female rats. The physicochemical characterization of NCs with different surface coatings: NC1 (Polysorbate 80), NC2 (PEG), NC3 (Eudragit®RS 100) and NC4 (Chitosan) were performed. Female rats were treated with saline, NC1, NC2, NC3 or NC4 daily for 14 days, p.o. After 24 h of last treatment, animals were submitted to behavioral tests. Only after behavioral tests, female rats were euthanized, organs were removed and weighted. After, histopathological, biochemical and oxidative stress analysis were performed. All NCs-coatings did not cause alterations in behavioral tests. For markers of hepatic, renal damage and lipid profile, the different coatings showed a low toxicity. NCs did not alter weight of organs and histopathological analysis. Also, all NCs-coatings did not modify redox balance in organs studied, only NC2 induced a increase of FRAP levels in intestine. This study demonstrated that the different NCs-coatings did not cause behavioral changes and showed a low toxicity in female rats.