A potential nanoparticle-loaded in situ gel for enhanced and sustained ophthalmic delivery of dexamethasone.

Increasing the permeability of drugs across the cornea is key to improving drug absorption by the eye. This study presents a newly developed in situ gel loaded with nanoparticles, which could achieve controlled drug release and high ocular drug bioavailability by avoiding rapid precorneal clearance. The physicochemical parameters of the formulation were investigated and showed uniform size, physical stability, and favorable rheological and gelling properties. Ex vivo permeation studies revealed significantly higher drug release from the in situ gel loaded with nanoparticles compared to the conventional poloxamer in situ gel and the drug solution. When compared with a marketed formulation, the in situ gel loaded with nanoparticles provided slower controlled release and higher ocular bioavailability of dexamethasone. In conclusion, the developed nanoparticle-loaded in situ gel can successfully increase drug ocular bioavailability by enhancing contact time with the ocular surface and permeation through the cornea.

Effect of a 2-HP-ß-Cyclodextrin Formulation on the Biological Transport and Delivery of Chemotherapeutic PLGA Nanoparticles.

BACKGROUND: The aim of this work was to develop a novel and feasible modification strategy by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-ß-CD) for enhancing the biological transport efficiency of paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles. METHODS: PTX-loaded 2-HP-ß-CD-modified PLGA nanoparticles (2-HP-ß-CD/PLGA NPs) were prepared using the modified emulsion method. Nano-characteristics, drug release behavior, in vitro cytotoxicity, cellular uptake profiles and in vivo bio-behavior of the nanoparticles were then characterized. RESULTS: Compared with the plain PLGA NPs, 2-HP-ß-CD/PLGA NPs exhibited smaller particle sizes (151.03±1.36 nm), increased entrapment efficiency (~49.12% increase) and sustained drug release. When added to A549 human lung cancer cells, compared with PLGA NPs, 2-HP-ß-CD/PLGA NPs exhibited higher cytotoxicity in MTT assays and improved cellular uptake efficiency. Pharmacokinetic analysis showed that the AUC value of 2-HP-ß-CD/PLGA NPs was 2.4-fold higher than commercial Taxol® and 1.7-fold higher than plain PLGA NPs. In biodistribution assays, 2-HP-ß-CD/PLGA NPs exhibited excellent stability in the circulation. CONCLUSION: The results of this study suggest that the formulation that contains 2-HP-ß-CD can prolong PTX release, enhance drug transport efficiency and serve as a potential tumor targeting system for PTX.

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.

Characterisation of 2-HP-ß-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles.

Aim: 2-HP-ß-cyclodextrin-PLGA nanoparticle complexes were prepared to enhance the aqueous humour delivery of Triamcinolone acetonide.Materials & methods: Drug-loaded 2-HP-ß-CD/PLGA nanoparticle complexes prepared by adapting a quasi-emulsion solvent evaporation technique. In vitro drug release, in vitro transcorneal permeation study, histopathological study and in vivo transcorneal penetration of PLGA nanoparticles and 2-HP-ß-CD/PLGA nanoparticle complexes were evaluated. Results: Particle size distributions of 2-HP-ß-CD/PLGA nanoparticle complexes were 149.4 ± 3.7 nm and presented stable system. Corneal penetration studies revealed steady sustained drug release (First-order); 2-HP-ß-CD/PLGA nanoparticle complexes increased ocular bioavailability by increasing dispersion in the tear film and improving drug release. Conclusion: 2-HP-ß-CD/PLGA nanoparticle complex formulation is a promising alternative to conventional eye drops.

Ruthenium complex delivery using liposomes to improve bioactivity against HeLa cells via the mitochondrial pathway.

AIM: The aim of this study was to encapsulate a ruthenium complex [Ru(ttbpy)2PIP](ClO4)2 (Ru) in liposomes to enhance their antitumor effect on human cervical cancer. METHODS: The Ru-loaded PEGylated liposomes (Ru-Lip) were prepared using thin-film hydration method. The mechanism of action was studied. RESULTS: A novel Ru was successfully synthesized. Ru-Lip showed stronger cytotoxic activity against HeLa cells than Ru. Ru-Lip demonstrated a more significant increase in apoptosis, reactive oxygen species production and apoptosis-associated processes (intracellular calcium concentration, cytochrome c release and activation of Bax and caspase-3) than Ru. Ru-Lip exhibited greater blockade efficacy in the cell cycle G1 phase and greater DNA damage than Ru. CONCLUSION: Ru-Lip significantly elevates the anticancer effect via reactive oxygen species-mediated mitochondrial dysfunctional pathway.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery.

AIM: The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. METHODS: In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. RESULTS: The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. CONCLUSION: The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.