Gadhave Dnyandev, Tupe Shrikant, Tagalpallewar Amol, Gorain Bapi, Choudhury Hira, Kokare Chandrakant
Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India; Department of Pharmaceutics, HSBPVTS, GOI, College of Pharmacy (Affiliated to Savitribai Phule Pune University), Kashti, Ahmednagar 414701, Maharashtra, India.
Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India.
Int J Pharm. 2021 Sep 25;607:121050. doi: 10.1016/j.ijpharm.2021.121050. Epub 2021 Aug 25.
Unfavorable side effects of available antipsychotics limit the use of conventional delivery systems, where limited exposure of the drugs to the systemic circulation could reduce the associated risks. The potential of intranasal delivery is gaining interest to treat brain disorders by delivering the drugs directly to the brain circumventing the tight junctions of the blood-brain barrier with limited systemic exposure of the entrapped therapeutic. Therefore, the present research was aimed to fabricate, optimize and investigate the therapeutic efficacy of amisulpride (AMS)-loaded intranasal in situ nanoemulgel (AMS-NG) in the treatment of schizophrenia. In this context, AMS nanoemulsion (AMS-NE) was prepared by employing aqueous-titration method and optimized using Box-Behnken statistical design. The optimized nanoemulsion was subjected to evaluation of globule size, transmittance, zeta potential, and mucoadhesive strength, which were found to be 92.15 nm, 99.57%, -18.22 mV, and 8.90 g, respectively. The AMS-NE was converted to AMS-NG using poloxamer 407 and gellan gum. Following pharmacokinetic evaluation in Wistar rats, the brain C for intranasal AMS-NG was found to be 1.48-folds and 3.39-folds higher when compared to intranasal AMS-NE and intravenous AMS-NE, respectively. Moreover, behavioral investigations of developed formulations were devoid of any extrapyramidal side effects in the experimental model. Finally, outcomes of the in vivo hematological study confirmed that intranasal administration of formulation for 28 days did not alter leukocytes and agranulocytes count. In conclusion, the promising results of the developed and optimized intranasal AMS-NG could provide a novel platform for the effective and safe delivery of AMS in schizophrenic patients.
现有抗精神病药物的不良副作用限制了传统给药系统的使用，在传统给药系统中，药物进入体循环的量有限，这可能会降低相关风险。鼻内给药的潜力正受到关注，通过将药物直接输送到大脑，绕过血脑屏障的紧密连接，同时使包封的治疗药物的全身暴露量有限，从而治疗脑部疾病。因此，本研究旨在制备、优化并研究载有氨磺必利（AMS）的鼻内原位纳米乳凝胶（AMS-NG）在治疗精神分裂症方面的疗效。在此背景下，采用水相滴定法制备了AMS纳米乳（AMS-NE），并使用Box-Behnken统计设计进行优化。对优化后的纳米乳进行了粒径、透光率、zeta电位和黏膜粘附强度的评估，结果分别为92.15 nm、99.57%、-18.22 mV和8.90 g。使用泊洛沙姆407和结冷胶将AMS-NE转化为AMS-NG。在Wistar大鼠中进行药代动力学评估后发现，与鼻内AMS-NE和静脉注射AMS-NE相比，鼻内AMS-NG的脑内药物浓度分别高出1.48倍和3.39倍。此外，对所开发制剂的行为学研究表明，在实验模型中没有任何锥体外系副作用。最后，体内血液学研究结果证实，鼻内给药该制剂28天不会改变白细胞和无粒细胞计数。总之，所开发和优化的鼻内AMS-NG的良好结果可为精神分裂症患者有效、安全地递送AMS提供一个新平台。
