Department of Pharmaceutics, School of Pharmaceutical Education and Research, New Delhi, India.
University College of Medical Sciences, University of Delhi, Dilshad Garden, New Delhi, India.
Drug Deliv. 2022 Dec;29(1):1409-1422. doi: 10.1080/10717544.2022.2069880.
Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidone-loaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70-98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant ( < .05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant ( < .01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the performance, and diminish the associated side effects.
抗精神病药伴随着锥体外系副作用，这会影响治疗的依从性和患者的顺应性。帕利哌酮（PPD）是一种推荐用于治疗精神分裂症的新型（第二代）抗精神病药，具有生物制药方面的挑战和药理学限制，使其无法穿过血脑屏障。本研究旨在评估载帕利哌酮的脂质纳米结构（PPD-LNC），以提高抗精神病活性，用于治疗精神分裂症。Neuro-2a 细胞的高细胞存活率（70-98%）表明 PPD-LNC 的安全性。药代动力学数据显示，与药物混悬剂相比，PPD-LNC 在大脑中的相对生物利用度提高了 3.46 倍。药效学评价表明，PPD-LNC 可显著减少（<0.05）僵住行为，降低逃避潜伏期，并延长在开放臂中的停留时间，从而显示其在减少锥体外系症状方面的有效性。组织病理学图像进一步验证了该配方的安全性。免疫组织化学分析显示 NF-κB 水平降低，表明 PPD-LNC 具有抗炎作用。该配方显著改善了氧化应激参数的活性，并减轻了神经炎症标志物。根据研究结果，我们发现，将 PPD 制成 LNC 将克服药理学限制，提高性能，并减少相关的副作用。
