a Department of Pharmaceutics, Bombay College of Pharmacy , Mumbai , Maharashtra , India.
b SPP School of Pharmacy and Technology Management , NMIMS University , Mumbai , India.
Curr Eye Res. 2019 May;44(5):575-582. doi: 10.1080/02713683.2019.1567793. Epub 2019 Jan 28.
A major challenge in ocular therapeutics is poor bioavailability of drug, 1% or even less of the instilled dose is absorbed and frequent administration of conventional products leads to poor adherence to therapy. Hence, the present study is to synthesize N-trimethyl chitosan (TMC), a water-soluble chitosan derivative and to prepare flurbiprofen (FLU):hydroxyl propyl-β-cyclodextrin (HP-β-CD) complex-loaded nanoparticles for treatment of bacterial conjunctivitis which aims to increase the residence time in ocular tissue, thus enhancing patient compliance and improved efficacy.
TMC was synthesized and characterized by H NMR and FT-IR. TMC and chitosan (CS) nanoparticles containing inclusion complex were prepared by ionic gelation using sodium tripolyphosphate (TPP). The nanoparticles thus obtained were evaluated for particle size, zeta potential, drug entrapment, in-vitro release, in-vitro mucoadhesion, and TEM for morphology and irritation potential was evaluated by the HET-CAM technique.
N-methyl quaternization of CS was confirmed by H NMR. The particle size and zeta potential of the TMC nanoparticles were found to be 201 ± 1.55 nm and +13.9 ± 1.697 mV and that of CS nanoparticles were 361.2 ± 1.55 nm and +10.9 ± 0.424 mV, respectively. The entrapment of FLU- HP-β-CD inclusion complex in polymeric nanoparticles was found to be 10.91 ± 1.541%. The observed in-vitro release profile of TMC nanoparticles indicated characteristic burst release followed by delayed release. HET-CAM studies demonstrated the ocular safety of TMC nanoparticles.
The developed TMC nanoparticles offered prolonged release potential for transmucosal ocular delivery of hydrophobic flurbiprofen.
眼部治疗的一个主要挑战是药物生物利用度差，只有 1%甚至更少的滴入剂量被吸收，而常规产品的频繁给药导致治疗依从性差。因此，本研究旨在合成 N-三甲基壳聚糖（TMC），一种水溶性壳聚糖衍生物，并制备氟比洛芬（FLU）：羟丙基-β-环糊精（HP-β-CD）复合物负载的纳米粒，用于治疗细菌性结膜炎，以增加在眼部组织中的停留时间，从而提高患者的依从性并提高疗效。
通过 H NMR 和 FT-IR 对 TMC 进行了合成和表征。TMC 和壳聚糖（CS）纳米粒包含包合复合物，通过使用三聚磷酸钠（TPP）的离子凝胶化法制备。所得纳米粒的粒径、Zeta 电位、药物包封率、体外释放、体外黏膜黏附性进行评价，并通过 HET-CAM 技术评价形态和刺激性。
CS 的 N-甲基季铵化通过 H NMR 得到证实。TMC 纳米粒的粒径和 Zeta 电位分别为 201±1.55nm 和+13.9±1.697mV，CS 纳米粒的粒径和 Zeta 电位分别为 361.2±1.55nm 和+10.9±0.424mV。FLU-HP-β-CD 包合物在聚合物纳米粒中的包封率为 10.91±1.541%。TMC 纳米粒的体外释放曲线呈特征性突释后延迟释放。HET-CAM 研究表明 TMC 纳米粒具有眼部安全性。
所开发的 TMC 纳米粒为疏水性氟比洛芬经黏膜眼部递药提供了延长释放的潜力。
