TY - JOUR
T1 - Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery
T2 - Preparation, mucoadhesion and pharmacokinetic evaluation
AU - Javed, Sadaf
AU - Abbas, Ghulam
AU - Shah, Shahid
AU - Rasul, Akhtar
AU - Irfan, Muhammad
AU - Saleem, Ammara
AU - Hosny, Khaled M.
AU - Bukhary, Sahar M.
AU - Safhi, Awaji Y.
AU - Sabei, Fahad Y.
AU - Majrashi, Mohammed A.
AU - Alkhalidi, Hala M.
AU - Alissa, Mohammed
AU - Khan, Sajid Mehmood
AU - Hanif, Muhammad
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - Antimicrobial activity
KW - Mucoadhesion
KW - Ocular irritation test
KW - Pharmacokinetics
KW - Sustainability of natural resources
KW - Thiolated chitosan
KW - nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=85172885085&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2023.e19877
DO - 10.1016/j.heliyon.2023.e19877
M3 - Article
AN - SCOPUS:85172885085
SN - 2405-8440
VL - 9
JO - Heliyon
JF - Heliyon
IS - 9
M1 - e19877
ER -