Cross-linked thermosensitive nanohydrogels for ocular drug delivery with a prolonged residence time and enhanced bioavailability.

AIM: A temperature-triggered, cross-linked nano hydrogel formulation (NPs-gel) was prepared to prolong the residence time of dexamethasone (DXM) in the eye and increase its bioavailability. RESEARCH DESIGN AND METHODS: The NPs-gel was prepared by combining a high pressure homogenization method with a cold solution method. Soy lecithin E200, lecithin oil, glycerol, kolliphor P188, kolliphor P407, and polycarbophil were the excipients used for the formation of NPs-gel containing DXM. The nanoparticle size, temperature-sensitive phase transition characteristics, in vitro and in vivo release behavior, corneal permeability, and eye irritation level of the NPs-gel were evaluated. RESULTS: The NPs-gel had slightly larger particle size than the DXM-loaded nanoparticles, yet it retained the properties of nanoparticles such as surface effect and size effect. The phase transition temperature was 33.2 °C, which is within the trigger conditions of intraocular temperature. Under physiological conditions, the adhesion and adhesion work of the NPs-gel were 1.1 and 2.1 times that of an in situ-formed gel, and the gel strength of NPs-gel was 1.8 times that of an in situ-formed gel. These results indicate that NPs-gel has greater adhesion and mechanical strength. The area under the curve of NPs-gel was 3.08 and 1.51 times that of DXM-loaded nanoparticles and in situ-formed gel, showing higher bioavailability. CONCLUSION: The NPs-gel is a suitable formulation to further enhance ocular drug delivery.

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.

PURPOSE: 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-ß-cyclodextrin (2-HP-ß-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-ß-CD/PLGA NPs showed the highest entrapment efficiency. In vitro evaluation and aqueous humor pharmacokinetics further revealed that 2-HP-ß-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-ß-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.