C. U. Shah College of Pharmacy, SNDT Women's University, Santacruz (W), Mumbai, Maharashtra, 400049, India.
AAPS PharmSciTech. 2024 Oct 21;25(8):247. doi: 10.1208/s12249-024-02964-x.
Iloperidone, a second-generation USFDA approved antipsychotic and BCS class II drug shows poor oral bioavailability of 28%. The present research deals with optimization of transnasal nanoemulsions of Iloperidone using Design Expert (Version 11) and further surface functionalization with chitosan for potentiating nose to brain delivery. Chitosan functionalized transnasal Iloperidone nanoemulsions were developed using oleic acid, charge inducer, Tween 80, Transcutol HP and chitosan using ultrasonication technique and evaluated. Droplet size, polydispersity index and zeta potential of Iloperidone nanoemulsions was found to be 173 ± 0.5 nm, 0.413 ± 0.2 and - 22.5 ± 0.1 mV while that of chitosan functionalized Iloperidone nanoemulsions was 146.4 ± 0.5 nm, 0.291 ± 0.02 and + 23.6 ± 0.3 mV respectively. Ninhydrin assay, TEM and FTIR studies confirmed surface functionalization of Iloperidone nanoemulsion droplets with chitosan. In vitro release of Iloperidone from nanoemulsions and chitosan functionalized nanoemulsions was 90.41 ± 2.1% and 72.02 ± 0.21% while ex vivo permeation of Iloperidone across goat nasal mucosa was 1270.58 ± 0.023 μg/cm and 1096.13 ± 0.043 μg/cm respectively at the end of 8 h. Studies in RPMI 2650 nasal and Neuro2A brain cell line lines indicated safety of chitosan functionalized transnasal Iloperidone nanoemulsions. Studies in Wistar rats showed increased cataleptic effects, reduced cognitive impairment and anxiety-related behaviour with greater brain accumulation indicating promising potential of this approach in nose to brain drug delivery.
依匹哌唑，一种第二代美国食品和药物管理局批准的抗精神病药物和 BCS 分类 II 药物，其口服生物利用度仅为 28%。本研究旨在使用 Design Expert（版本 11）优化依匹哌唑的经鼻纳米乳，并进一步用壳聚糖进行表面功能化，以增强鼻内递药至脑内的效果。采用油酸、电荷诱导剂、吐温 80、Transcutol HP 和壳聚糖，通过超声技术制备并评价了壳聚糖功能化的经鼻依匹哌唑纳米乳。依匹哌唑纳米乳的粒径、多分散指数和 Zeta 电位分别为 173±0.5nm、0.413±0.2 和-22.5±0.1mV，而壳聚糖功能化的依匹哌唑纳米乳的粒径、多分散指数和 Zeta 电位分别为 146.4±0.5nm、0.291±0.02 和+23.6±0.3mV。茚三酮试验、TEM 和 FTIR 研究证实了依匹哌唑纳米乳滴的表面壳聚糖功能化。纳米乳和壳聚糖功能化纳米乳中依匹哌唑的体外释放分别为 90.41±2.1%和 72.02±0.21%，而依匹哌唑在山羊鼻黏膜中的体外渗透分别为 1270.58±0.023μg/cm 和 1096.13±0.043μg/cm，在 8 小时末。RPMI 2650 鼻细胞和 Neuro2A 脑细胞系的研究表明壳聚糖功能化的经鼻依匹哌唑纳米乳是安全的。在 Wistar 大鼠中的研究表明，该方法可增强猫瘫作用，减少认知障碍和焦虑相关行为，增加大脑积累，表明该方法在鼻内递药至脑内具有潜在的应用前景。
