In this study, olanzapine-loaded lipid-core nanocapsules were successfully developed and coated with two different chitosan solutions (same concentration of chitosan but either in 1% acetic acid solution or in acetate buffer pH 5.5) aiming to increase the mucoadhesion and the brain delivery of olanzapine in order to improve the antipsychotic effect after oral administration. These nanoformulations underwent a full physicochemical characterization followed by efficacy evaluation in PPI in rats. The formulation selected for the PPI study (nanocapsules coated with chitosan solution in sodium acetate buffer pH 5.5, NCOLA-B) showed pH of 5.9 ± 0.2, diameter of 162 ± 12 nm with polydispersity index of 0.24 ± 0.01, zeta potential of +6.9 ± 0.7 mV, drug content of 1.06 mg.mL⁻¹ with 42.2% of encapsulation efficiency. Moreover, the nanocapsules showed spherical shape by transmission electron microscopy, suitable physical stability by multiple light scattering, control of drug release (dialysis bag method), low viscosity with Newtonian behavior and great mucin adhesion capacity. Unlike olanzapine solution (10 mg.mL⁻¹), NCOLA-B (1 mg.mL⁻¹) prevented the PPI disruption induced by apomorphine (4 mg.kg⁻¹, s.c.) when administered by the oral route. In conclusion, these findings open new possibilities for the nanoformulation composed of nanocapsules coated with chitosan as a novel strategy for olanzapine delivery.

在这项研究中，成功​​开发了装载奥氮平的脂质核心纳米胶囊，并用两种不同的壳聚糖溶液（相同浓度的壳聚糖，但在1％乙酸溶液中或在pH 5.5的乙酸盐缓冲液中）包被，旨在增加粘膜黏附和脑部递送口服奥氮平以改善抗精神病作用。对这些纳米制剂进行了完整的理化表征，然后在大鼠中对PPI进行了功效评估。用于PPI研究的制剂（在乙酸钠缓冲液pH 5.5中使用壳聚糖溶液包被的纳米胶囊，NCOLA-B）的pH为5.9±0.2，直径为162±12 nm，多分散指数为0.24±0.01，ζ电位为+6.9 ±0.7 mV，药物含量为1.06 mg.mL ^-1封装效率为42.2％。此外，纳米胶囊通过透射电子显微镜显示球形，通过多次光散射具有合适的物理稳定性，控制药物释放（透析袋法），具有牛顿行为的低粘度和大的粘蛋白粘附能力。与奥氮平溶液（10 mg.mL ^-1）不同，NCOLA-B（1 mg.mL ^-1）通过口服途径预防由阿扑吗啡（4 mg.kg ^-1，sc）引起的PPI破坏。总之，这些发现为由纳米胶囊包被壳聚糖组成的纳米制剂作为奥氮平释放的新策略开辟了新的可能性。