El Sisi Amani M, Eissa Essam M, Hassan Ahmed H E, Bekhet Marina A, El-Ela Fatma I Abo, Roh Eun Joo, Kharshoum Rasha M, Ali Adel A
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Pharmaceuticals (Basel). 2025 Jan 3;18(1):46. doi: 10.3390/ph18010046.
: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repeated administration. The current inquiry intended to fabricate nose-to-brain chitosan-grafted cationic leciplexes of MRZ (CS-MRZ-LPX) to improve its pharmacokinetic weaknesses and boost the pharmacodynamics aspects. : Primarily, MRZ-loaded leciplexes (MRZ-LPXs) were fabricated and tailored employing a central composite design (CCD). Vesicle diameter size (VS), entrapment efficiency (EE %), cumulative MRZ release percentage (CMRZR %), and total quantity penetrating after twenty-four hours (Q24) were the four parameters assessed. Then, the determined optimum formulation was coated with chitosan (CS-MRZ-LPX) and utilized in pharmacodynamics investigations and in vivo biologic distribution studies in Wistar male rats. : The customized MRZ-LPX formulation had a diameter size of 186.2 ± 3.5 nm and drug EE of 45.86 ± 0.76%. Also, the tailored MRZ-LPX formulation had a cumulative amount of MRZ released of 76.66 ± 3.06% and the total Q24 permeated was 383.23 ± 13.08 µg/cm. Intranasal delivery of the tailored CS-MRZ-LPX revealed notably superior pharmacokinetic attributes inside the brain and circulation compared to the orally administered MRZ suspension and the intranasal free drug suspension ( < 0.05); the relative bioavailability was 370.9% and 385.6% for plasma and brain, respectively. Pharmacodynamics' and immunohistopathological evaluations proved that optimum intranasal CS-MRZ-LPX boosted antidepressant activity compared to the oral and free nasal drug administration. : CS-MRZ-LPX tailored formulation can potentially be regarded as a prospective nano platform to boost bioavailability and enhance pharmacodynamics efficacy. Ultimately, intranasal CS-MRZ-LPX can be considered a promising avenue for MRZ targeted brain delivery as an antidepressant.
米氮平（MRZ）是一种用于治疗重度抑郁症的精神药物。由于其广泛的首过代谢过程且水溶性差，口服时最终生物利用度仅为50%，需要重复给药。当前研究旨在制备米氮平的鼻脑靶向壳聚糖接枝阳离子脂质复合物（CS-MRZ-LPX），以改善其药代动力学弱点并增强药效学方面。：首先，采用中心复合设计（CCD）制备并定制了载米氮平脂质复合物（MRZ-LPXs）。评估了四个参数，即囊泡直径大小（VS）、包封率（EE%）、米氮平累积释放百分比（CMRZR%）和24小时后穿透总量（Q24）。然后，将确定的最佳制剂用壳聚糖包衣（CS-MRZ-LPX），并用于药效学研究以及Wistar雄性大鼠的体内生物分布研究。：定制的MRZ-LPX制剂直径大小为186.2±3.5nm，药物包封率为45.86±0.76%。此外，定制的MRZ-LPX制剂米氮平累积释放量为76.66±3.06%，24小时渗透总量Q24为383.23±13.08μg/cm。与口服米氮平混悬液和鼻内游离药物混悬液相比，定制的CS-MRZ-LPX鼻内给药在脑内和循环中的药代动力学特性显著更优（P<0.05）；血浆和脑的相对生物利用度分别为370.9%和385.6%。药效学和免疫组织病理学评估证明，与口服和鼻内游离药物给药相比，最佳鼻内CS-MRZ-LPX增强了抗抑郁活性。：CS-MRZ-LPX定制制剂有可能被视为提高生物利用度和增强药效学功效的潜在纳米平台。最终，鼻内CS-MRZ-LPX可被视为米氮平作为抗抑郁药靶向脑递送的有前景途径。
