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.

Objectives: Investigating how nanoparticle systems interact in whole blood (WB) is critical to evaluating the effectiveness of malaria therapy. Methods: We decided to establish a pharmacokinetic/pharmacodynamic (PK/PD) model of the quinine population in WB using Plasmodium berghei-infected mice, with a subsequent model comparison for nanocapsules coated with polysorbate (NCP80) or prepared with Eudragit^® RS (NCEUD). The WB quinine population pharmacokinetic model in rats was developed using plasma and partition coefficients for rat erythrocytes. Mouse WB quinine population PK/PD modeling was developed using allometrically scaled literature-free mouse quinine pharmacokinetic data and covariate values to obtain a WB population pharmacokinetic model for quinine and nanocapsules in mice. This allowed for PK/PD modeling of the quinine population with the WB concentration and parasitemia data in mice. All models were built in NONMEN. Results: The WB quinine concentration profiles in rats were characterized using a two-compartment model. Nanoencapsulation reduced clearance and central compartment volume and increased peripherical compartimental volume. A maximum effect model described the PK/PD of the quinine WB population in mice, demonstrating that NCEUD enhances the antimalarial effect. Conclusions: Quinine WB is a good surrogate for describing the response to exposure in malaria. NCEUD outperformed NCP80 and free quinine, suggesting that cationic surfaces improve the potential for treating malaria.

This study evaluated the antiseptic effect of 0.25% chlorhexidine nanoemulsion (NM-Cl) on cat skin and compare its effect with that of 2.0% chlorhexidine digluconate (CS-Cl). NM-Cl was synthesized using the spontaneous emulsification method, and physical and chemical properties were analyzed. The antiseptic effects of NM-Cl and CS-Cl were randomly tested on the thoracic limbs of 10 healthy male cats. After a wide trichotomy of the thoracic limbs, NM-Cl was randomly applied to the trichotomy area of the right (n = 5) or left (n = 5) thoracic limbs. Then, a catheter was inserted aseptically in the cephalic vein. Subsequently, the same procedure was performed using CS-Cl on the contralateral limb. Cutaneous microbiota swab samples were obtained before antisepsis (Tpre); immediately after antisepsis (Tpost); and 4, 8, and 24 h after antisepsis. The collected samples were immediately inoculated on blood agar plates and incubated at 35 ºC ± 2 ºC in aerobiosis. Colony-forming units (CFUs) were manually counted after 24 h of inoculation. The Kruskal-Wallis and Mann-Whitney U tests were performed between groups and within the same group at different sample times, respectively. The NM-Cl and CS-Cl groups showed a reduction in CFUs between Tpre and Tpost in all animals (P < 0.001). Both formulations presented an antiseptic effect 24 h of antisepsis (P < 0.05), and no difference was observed between formulations at different times (P < 0.05). With a lower concentration of chlorhexidine than CS-Cl, NM-Cl presents effective antiseptic action and prolonged residual effect in antisepsis for cat venipuncture.

Background/Objectives: Meloxicam (MLX) is a nonsteroidal anti-inflammatory drug (NSAID) recommended for treating acute and chronic pain in dogs, frequently administered prophylactically to mitigate postoperative pain; however, its utility is limited by characteristic NSAID-associated adverse effects, such as gastrointestinal side effects. Nanosystems offer the potential to minimize adverse effects by sustaining drug release. Therefore, this study assessed the pharmacokinetics of MLX nanoencapsulation in female dogs undergoing ovariohysterectomy using a population pharmacokinetic (PopPK) modeling approach. Methods: MLX-loaded polymeric nanocapsules (NC-MLX) were prepared using the nanoprecipitation method and characterized by zeta potential, pH, mean diameter, particle size distribution, and drug content. Dogs received 0.2 mg/kg of either NC-MLX or free MLX orally, 4 h before surgery, and plasma samples were analyzed using an HPLC-PDA method. Pharmacokinetics were characterized by non-compartmental analysis and PopPK modeling. Several compartmental structures, variability models, and residual error models were explored, and relevant covariates were investigated. Results: NC-MLX had an average diameter of 326 ± 13 nm, a zeta potential of −26.2 ± 6.4 mV, and drug loading of 99.47% ± 0.01%. NC-MLX showed a significant increase in the t_1/2 (36.99 ± 17.26 h) of MLX compared to the free drug (15.22 ± 4.4 h). The best-fitting PopPK model was a two-compartment model with double extravascular first-order absorption rate constants (Ka₁ and Ka₂), including a lag time for Ka₂ and linear elimination, describing the second peak observed in several animals. The nanoformulation was a significant covariate for Tlag₂, delaying the time for absorption (1.22 and 2.55 h for free MLX and NC-MLX, respectively) and increasing V₂ (0.134 and 0.402 L/kg for free MLX and NC-MLX, respectively). External model validation showed that the final PopPK model accurately predicted plasma concentrations, with MPE% and RMSE values below 15%. Conclusions: Our findings suggest that NC-MLX alters MLX absorption and distribution profiles, supporting its potential as an alternative for postoperative pain management in dogs.