PLGA公司
鼻腔给药
生物利用度
药理学
药代动力学
壳聚糖
渗透
化学
药效学
离体
最大值
口服
医学
有机化学
体外
生物化学
膜
作者
Heba F. Salem,Adel A. Ali,Yasmine K. Rabea,Fatma I. Abo El‐Ela,Rasha A. Khallaf
标识
DOI:10.1016/j.xphs.2022.08.034
摘要
Duloxetine HCl (DXH) is a psychiatric medicine employed for treating major depressive disorder. Nonetheless, its low water solubility, high first-pass metabolism, and acid instability diminish the absolute oral bioavailability to 40%, thus necessitating frequent administration. Therefore, the aim of the current study was to formulate DXH as nasal chitosan-grafted polymeric nanoparticles to improve its pharmacokinetic and pharmacodynamic properties. Applying the Box-Behnken design, DXH loaded PLGA-Chitosan nanoparticles (DXH-PLGA-CS-NPs) were fabricated and optimized using polylactide-co-glycolic acid (PLGA), chitosan (CS), and polyvinyl alcohol (PVA) as the independent factors. Particle size, entrapment efficiency, release percent, and cumulative amount permeated after 24 h of DXH-PLGA-CS-NPs (dependent variables) were evaluated. The in-vivo biodistribution and pharmacodynamic studies were done in male Wistar rats. The optimized DXH-PLGA-CS-NPs had a vesicle size of 122.11 nm and EE% of 66.95 with 77.65% release and Q24 of 555.34 (µg/cm2). Ex-vivo permeation study revealed 4-folds increase in DXH permeation from DXH-PLGA-CS-NPs after 24 h compared to DXH solution. Intranasal administration of optimized DXH-PLGA-CS-NPs resulted in significantly higher (p < 0.05) Cmax, AUCtotal, t1/2, and MRT in rat brain and plasma than oral DXH solution. Pharmacodynamics investigation revealed that intranasally exploited optimal DXH-PLGA-CS-NPs could be deemed a fruitful horizon for DXH as a treatment for depression.
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