Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery: Preparation, mucoadhesion and pharmacokinetic evaluation

Sadaf Javed; Ghulam Abbas; Shahid Shah; Akhtar Rasul; Muhammad Irfan; Ammara Saleem; Khaled M Hosny; Sahar M Bukhary; Awaji Y Safhi; Fahad Y Sabei; Mohammed A Majrashi; Hala M Alkhalidi; Mohammed Alissa; Sajid Mehmood Khan; Muhammad Hanif

doi:10.1016/j.heliyon.2023.e19877

Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery: Preparation, mucoadhesion and pharmacokinetic evaluation

Heliyon. 2023 Sep 7;9(9):e19877. doi: 10.1016/j.heliyon.2023.e19877. eCollection 2023 Sep.

Authors

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad 38000, Pakistan.
² Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Government College University Faisalabad 38000, Pakistan.
³ Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad 38000, Pakistan.
⁴ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Biological Analysis, Neuroscience unit, King Abdulaziz University, Jeddah, Saudi Arabia.
⁶ Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
⁷ Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah 23890, Saudi Arabia.
⁸ Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
⁹ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
¹⁰ Faculty of Pharmacy and Alternative Medicine, The Islamia University Bahawalpur, Pakistan.
¹¹ Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan, Pakistan.

Abstract

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 ¹H NMR and FTIR, which showed peaks at 6.6 ppm and 1230 cm^-1, 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 Pseudomonas aeruginosa. The optimized formulation NT8 (0.1% TRM) greatly increased the AUC_(0-∞) (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.

Keywords: Antimicrobial activity; Mucoadhesion; Ocular irritation test; Pharmacokinetics; Sustainability of natural resources; Thiolated chitosan; nanoparticles.