Cayero-Otero M Dolores, Perez-Caballero Laura, Suarez-Pereira Irene, Hidalgo-Figueroa María, Delgado-Sequera Alejandra, Montesinos Juan Manuel, Berrocoso Esther, Martín-Banderas Lucía
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad de Sevilla, Sevilla, Spain.
Department of Psychobiology, University of Granada, Campus de Cartuja, Granada, Spain.
Int J Pharm. 2025 Jun 10;678:125692. doi: 10.1016/j.ijpharm.2025.125692. Epub 2025 May 13.
Current treatment of depression is hindered by the delayed onset of the action of antidepressant drugs, often resulting in treatment failure. Therefore, new therapeutic solutions are imperative.
Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were produced by a double emulsion-solvent evaporation method. Cellular safety assessment and internalization assays were carried out in vitro in human olfactory neuroepithelium cells. The antidepressant effect of intranasal (nose-to-brain) nanoparticle administration was assessed in animals submitted to an animal model of depression by behavioral tests, including open-field, sucrose preference test and tail suspension test.
The drug entrapment efficiency (55-65 %), particle size (190-210 nm), polydispersity index (<0.2), and zeta potential (-20 mV) of Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were determined to be adequate. Nanoparticles did not show cytotoxic effects. Cell viability was more than 90 % for all formulations and concentrations assayed. The results of the quantitative and qualitative cell uptake assays were consistent, showing an evident internalization of the nanoparticles into the cells. Furthermore, venlafaxine-loaded nanoparticles administered for just 7 days were able to reverse the phenotype induced by a depressive-like model, showing a significant antidepressant-like effect compared to those treated with free venlafaxine.
These findings indicated that intranasal venlafaxine-loaded poly(lactic-coglycolic acid) nanoparticles could become a viable technique for improving venlafaxine brain uptake via nose-to-brain. It could also be a promising nanoplatform for enhancing the treatment of depression.
抗抑郁药物作用起效延迟阻碍了当前抑郁症的治疗，常导致治疗失败。因此，新的治疗方案势在必行。
采用双乳液-溶剂蒸发法制备了载有文拉法辛的聚乳酸-羟基乙酸共聚物纳米粒。在人嗅神经上皮细胞中进行了体外细胞安全性评估和内化试验。通过行为测试，包括旷场试验、蔗糖偏好试验和悬尾试验，在建立了抑郁症动物模型的动物中评估了鼻内（鼻至脑）纳米粒给药的抗抑郁作用。
测定载有文拉法辛的聚乳酸-羟基乙酸共聚物纳米粒的药物包封率（55 - 65%）、粒径（190 - 210 nm）、多分散指数（<0.2）和zeta电位（-20 mV）均合适。纳米粒未显示出细胞毒性作用。所有测定的制剂和浓度下细胞活力均超过90%。定量和定性细胞摄取试验结果一致，表明纳米粒明显内化进入细胞。此外，仅给药7天的载文拉法辛纳米粒就能逆转抑郁样模型诱导的表型，与游离文拉法辛治疗组相比显示出显著的抗抑郁样效果。
这些发现表明，鼻内给予载有文拉法辛的聚乳酸-羟基乙酸共聚物纳米粒可能成为一种通过鼻至脑途径提高文拉法辛脑摄取的可行技术。它也可能是一种有前景的纳米平台，用于加强抑郁症的治疗。
