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用于增强盐酸丁苯那嗪鼻脑递送的热可逆离子凝胶:采用中心复合设计进行优化及体外和离体评价

Thermoreversible Ionogel for Enhanced Nose-to-brain Delivery of Tetrabenazine Hydrochloride: Optimization by Central Composite Design and In Vitro Ex Vivo Evaluation.

作者信息

Jadhav Namdeo, Chavan Manali, Patil Prathamesh, Takale Pranali, Mane Megha, Mohite Suhas

机构信息

Krishna Vishwa Vidyapeeth (Deemed to Be University), Krishna Institute of Pharmacy, Karad, Maharashtra, India, 415539.

Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India, 416013.

出版信息

AAPS PharmSciTech. 2025 Aug 11;26(7):210. doi: 10.1208/s12249-025-03203-7.

Abstract

Bio-ionic liquid (BIL)-based ionogels have been researched for improved solubility, permeability, and bioavailability of poorly soluble drug/s. This study aimed to develop a thermoreversible ionogel for nose-to-brain delivery (NBD) of Tetrabenazine hydrochloride (TBZ), a BCS Class IV drug. Initially, a BIL-based micellar system of TBZ was developed using choline oleate ([Cho][Ole]) and decorated with Pluronic F-127 (PF-127). Further, the micellar system was formulated as a thermoreversible ionogel and optimized using central composite design (CCD). The resulting TBZ-[Cho][Ole]-PF-127, an optimized ionogel was evaluated for drug loading, particle size, polydispersity, zeta potential, morphology, pH, gelation behavior, mucoadhesive strength, and drug release (in vitro and ex vivo). All ionogel batches exhibited suitable physicochemical characteristics for NBD. TBZ-[Cho][Ole] micelles demonstrated a particle size of 94.23 ± 0.76 nm, whereas the optimized ionogel exhibited a size of 164.98 ± 0.89 nm, significantly smaller than the plain gel (247.65 ± 1.93 nm) at p < 0.05. The optimized ionogel showed a zeta potential of -38.12 ± 1.64 mV, drug loading of 37.92 ± 1.45%, and entrapment efficiency of 83.12 ± 2.53%. SEM and TEM studies confirmed that spherical micelles have the desired particle size. Ionogel in vitro and ex vivo evaluations divulged 1.37-fold and 1.42-fold enhancements in drug release and permeation, respectively, over plain gel (p < 0.05), following zero-order kinetics. Short-term stability studies further confirmed the robustness of the formulation. Conclusively, the ionogel demonstrated improved delivery of TBZ, opening up the vista of BIL and ionogel customizability for NBD for diverse drug/s used in the management of neurological disorders.

摘要

基于生物离子液体(BIL)的离子凝胶已被研究用于改善难溶性药物的溶解度、渗透性和生物利用度。本研究旨在开发一种用于盐酸丁苯那嗪(TBZ,一种BCS IV类药物)鼻脑递送(NBD)的热可逆离子凝胶。最初,使用油酸胆碱([Cho][Ole])开发了基于BIL的TBZ胶束系统,并用泊洛沙姆F - 127(PF - 127)进行修饰。进一步地,将该胶束系统制成热可逆离子凝胶,并采用中心复合设计(CCD)进行优化。对所得的TBZ - [Cho][Ole] - PF - 127优化离子凝胶进行载药量、粒径、多分散性、zeta电位、形态、pH值、凝胶化行为、粘膜粘附强度和药物释放(体外和离体)评估。所有离子凝胶批次均表现出适合鼻脑递送的理化特性。TBZ - [Cho][Ole]胶束的粒径为94.23±0.76 nm,而优化后的离子凝胶粒径为164.98±0.89 nm,在p < 0.05时显著小于空白凝胶(247.65±1.93 nm)。优化后的离子凝胶zeta电位为 - 38.12±1.64 mV,载药量为37.92±1.45%,包封率为83.12±2.53%。扫描电子显微镜(SEM)和透射电子显微镜(TEM)研究证实球形胶束具有所需的粒径。离子凝胶的体外和离体评估显示,与空白凝胶相比,药物释放和渗透分别提高了1.37倍和1.42倍(p < 0.05),遵循零级动力学。短期稳定性研究进一步证实了该制剂的稳定性。总之,该离子凝胶证明了TBZ递送的改善,为用于神经疾病管理的多种药物的鼻脑递送开辟了BIL和离子凝胶可定制性的前景。

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