A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations

Abstract

ABSTRACT. Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

“…The average particle size of the cubosomes nanoparticles as well as their size distribution (polydispersity index; PDI) were measured by a particle analyzer (Zetasizer Nano ZS, Malvern (Salama et al, 2016) was dispersed in acetonitrile and were vortexed for 10 min (Reax top, Heidolph, Germany). The drug content was then analyzed by LC-MS/MS method following the procedure reported below.…”

Advances and limitations of drug delivery systems formulated as eye drops

“…For example, chitosan was used as a coating for PLGA NPs and showed a sustained delivery of forskalin and thus, a greater IOP lowering effect and duration compared to standard forskalin solution. Chitosan-coated PLGA NPs have also been used to deliver fluocinolone to the anterior segment of rabbit eyes [98]. Results showed that chitosan coating increased and sustained drug release by PLGA NPs.…”

Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

“…The results concerning both the coating with NACCS compared to CS oligosaccharides or carboxymethyl CS [312], as well as the content of thiol groups [313], were the same ( Figure 22B). Salama et al used PLGA 50/50 or 75/25 in NP formulation of fluocinolone acetonide (FA), which is an anti-inflammatory corticosteroid drug used for the treatment of intermediate, posterior, and pan uveitis [314]. NPs were prepared by an innovative thin film hydration process using P407 in a mass ratio of PLGA/P407 1:5 and 1:10.…”