<p>PLGA Nanoparticle Platform for Trans-Ocular Barrier to Enhance Drug Delivery: A Comparative Study Based on the Application of Oligosaccharides in the Outer Membrane of Carriers</p>

Abstract

The trans-ocular barrier is a key factor limiting the therapeutic efficacy of triamcinolone acetonide. We developed a poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) surface modified respectively with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), chitosan oligosaccharide and trehalose. Determination of the drug/nanoparticles interactions, characterization of the nanoparticles, in vivo ocular compatibility tests, comparisons of their corneal permeability and their pharmacokinetics in aqueous humor were carried out. Methods: All PLGA NPs were prepared by the single emulsion and evaporation method and the drug-nanoparticle interaction was studied. The physiochemical features and in vitro corneal permeability of NPs were characterized while the aqueous humor pharmacokinetics was performed to evaluate in vivo corneal permeability of NPs. Ocular compatibility of NPs was investigated through Draize and histopathological test. Results: The PLGA NPs with lactide/glycolide ratio of 50:50 and small particle size (molecular weight 10 kDa) achieved optimal drug release and corneal permeability. Surface modification with different oligosaccharides resulted in uniform particle sizes and similar drug-nanoparticle interactions, although 2-HP-β-CD/PLGA NPs showed the highest entrapment efficiency. In vitro evaluation and aqueous humor pharmacokinetics further revealed that 2-HP-β-CD/PLGA NPs had greater trans-ocular permeation and retention compared to chitosan oligosaccharide/PLGA and trehalose/PLGA NPs. No ocular irritation in vivo was detected after applying modified/unmodified PLGA NPs to rabbit's eyes. Conclusion: 2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.

Breaking Barriers in Eye Treatment: Polymeric Nano-Based Drug-Delivery System for Anterior Segment Diseases and Glaucoma

“…Their size and surface potential can be enhanced, which selectively alters their membrane permeability. Jiang et al compared several commonly used PLGA copolymeric nanoparticles and identified that copolymers consisting of hydroxypropyl-β-cyclodextrin and PLGA had the highest entrapment efficiency and trans-ocular permeation [ 15 ]. PLGA can also be modified with the use of polyethylene glycol (PEG), to construct biocompatible nanoparticles with sustained drug release and high entrapment efficiency profiles.…”

“…This is especially important for glaucoma drugs such as brinzolamide, which has low solubility and thereby limits its therapeutic efficacy. Various studies have formulated PLGA-modified (Polylactic-co-glycolic acid) nanoparticles to have a sustained release of brinzolamide that significantly reduced IOP in animal models with minimal toxicity [ 15 , 46 , 47 ]. Song et al (2020) used a coaxial electrospray technique to coat PLGA nanoparticles with phosphatidylserine (PS), improving entrapment efficiency and corneal permeation with topical delivery of brinzolamide.…”

Ethosomal Nanoformulations for Combinational Photothermal Therapy of Fungal Keratitis

“…After the final observation, the animals were euthanized, and the eyeballs were stained with H&E for histopathological study. [53][54][55][56]…”

Development of Chitosan–Tripolyphosphate Nanoparticles as Glycopeptide Antibiotic Reservoirs and Ex vivo Evaluation for Their Potential to Enhance the Corneal Permeation in Ocular Drug Delivery

“…The apparent corneal permeability coefficient (Papp) was calculated by the following equation where the ΔQ/Δt (μg/min) stands for the slope of the steady-state part of the cumulative permeation versus time graph, A stands for the effective corneal penetration area (cm 2 ) and C0 defined as the concentration of drug at the donor compartment (μg/mL). 26 𝑃 𝑎𝑝𝑝 = ∆𝑄 ∆𝑡.𝐴.𝐶 0 (Equation 4)…”