Javed Sadaf, Abbas Ghulam, Shah Shahid, Rasul Akhtar, Irfan Muhammad, Saleem Ammara, Hosny Khaled M, Bukhary Sahar M, Safhi Awaji Y, Sabei Fahad Y, Majrashi Mohammed A, Alkhalidi Hala M, Alissa Mohammed, Khan Sajid Mehmood, Hanif Muhammad
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad 38000, Pakistan.
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University Faisalabad 38000, Pakistan.
Heliyon. 2023 Sep 7;9(9):e19877. doi: 10.1016/j.heliyon.2023.e19877. eCollection 2023 Sep.
The present work aimed to develop nanoparticles of tobramycin (TRM) using thiolated chitosan (TCS) in order to improve the mucoadhesion, antibacterial effect and pharmacokinetics. The nanoparticles were evaluated for their compatibility, thermal stability, particle size, zeta potential, mucoadhesion, drug release, kinetics of TRM release, corneal permeation, toxicity and ocular irritation. The thiolation of chitosan was confirmed by H NMR and FTIR, which showed peaks at 6.6 ppm and 1230 cm, respectively. The nanoparticles had a diameter of 73 nm, a negative zeta potential (-21 mV) and a polydispersity index of 0.15. The optimized formulation, NT8, exhibited the highest values of mucoadhesion (7.8 ± 0.541h), drug loading (87.45 ± 1.309%), entrapment efficiency (92.34 ± 2.671%), TRM release (>90%) and corneal permeation (85.56%). The release pattern of TRM from the developed formulations was fickian diffusion. TRM-loaded nanoparticles showed good antibacterial activity against . The optimized formulation NT8 (0.1% TRM) greatly increased the AUC (1.5-fold) while significantly reducing the clearance (5-fold) compared to 0.3% TRM. Pharmacokinetic parameters indicated improved ocular retention and bioavailability of TRM loaded nanoparticles. Our study demonstrated that the TRM-loaded nanoparticles had improved mucoadhesion and pharmacokinetics and a suitable candidate for effective treatment of ocular bacterial infections.
本研究旨在使用硫醇化壳聚糖（TCS）制备妥布霉素（TRM）纳米颗粒，以改善其粘膜粘附性、抗菌效果和药代动力学。对纳米颗粒的相容性、热稳定性、粒径、zeta电位、粘膜粘附性、药物释放、TRM释放动力学、角膜渗透性、毒性和眼部刺激性进行了评估。通过1H NMR和FTIR证实了壳聚糖的硫醇化，分别在6.6 ppm和1230 cm处出现峰。纳米颗粒的直径为73 nm，zeta电位为负（-21 mV），多分散指数为0.15。优化后的制剂NT8表现出最高的粘膜粘附值（7.8±0.541 h）、载药量（87.45±1.309%）、包封率（92.34±2.671%）、TRM释放率（>90%）和角膜渗透率（85.56%）。TRM从所开发制剂中的释放模式为菲克扩散。载有TRM的纳米颗粒对……显示出良好的抗菌活性。与0.3%的TRM相比，优化后的制剂NT8（0.1%的TRM）使AUC大幅增加（1.5倍），同时显著降低清除率（5倍）。药代动力学参数表明载有TRM的纳米颗粒的眼部滞留和生物利用度得到改善。我们的研究表明，载有TRM的纳米颗粒具有改善的粘膜粘附性和药代动力学，是有效治疗眼部细菌感染的合适候选物。
