Wound-healing with mechanically robust and biodegradable hydrogel fibers loaded with silver nanoparticles.

The objective of this study is to provide a novel synthetic approach for the manufacture of wound-healing materials using covalently cross-linked alginate fibers loaded with silver nanoparticles. Alginate fibers are prepared by wet-spinning in a CaCl(2) precipitation bath. Using this same approach, calcium cross-links in alginate fibers are replaced by chemical cross-links that involve hydroxyl groups for subsequent cross-linking by glutaraldehyde. The cross-linked fibers become highly swollen in aqueous solution due to the presence of carboxyl functional groups, and retain their mechanical stability in physiological fluids owing to the stabilized network of covalent bonds. Alginate fibers can then be loaded with silver ions via the ion-exchange reaction. Silver ions are reduced to yield 11 nm silver nanoparticles incorporated in the polymer gel. This method provides a convenient platform to incorporate silver nanoparticles into alginate fibers in controlled concentrations while retaining the mechanical and swelling properties of the alginate fibers. Our study suggests that the silver nanoparticles loaded fibers may be easily applied in a wound healing paradigm and promote the repair process though the promotion of fibroblast migration to the wound area, reduction of the inflammatory phase, and the increased epidermal thickness in the repaired wound area, thereby improving the overall quality and speed of healing.

Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria.

Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25-60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory-Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.

Thermosensitive dendrimer formulation for drug delivery at physiologically relevant temperatures.

A simple and versatile dendrimer based platform to deliver therapeutic agents at temperatures within the physiological range, is reported. Lipoic acid conjugated at the periphery of the thermosensitive dendrimer formulations undergoes slow and sustained release at 37-42 °C, and rescues the cells from oxidative stress and a pro-inflammatory endotoxic agent.

Short ligands affect modes of QD uptake and elimination in human cells.

In order to better understand nanoparticle uptake and elimination mechanisms, we designed a controlled set of small, highly fluorescent quantum dots (QDs) with nearly identical hydrodynamic size (8-10 nm) but with varied short ligand surface functionalization. The properties of functionalized QDs and their modes of uptake and elimination were investigated systematically by asymmetrical flow field-flow fractionation (AF4), confocal fluorescence microscopy, flow cytometry (FACS), and flame atomic absorption (FAA). Using specific inhibitors of cellular uptake and elimination machinery in human embryonic kidney cells (Hek 293) and human hepatocellular carcinoma cells (Hep G2), we showed that QDs of the same size but with different surface properties were predominantly taken up through lipid raft-mediated endocytosis, however, to significantly different extents. The latter observation infers the contribution of additional modes of QD internalization, which include X-AG cysteine transporter for cysteine-functionalized QDs (QD-CYS). We also investigated putative modes of QD elimination and established the contribution of P-glycoprotein (P-gp) transporter in QD efflux. Results from these studies show a strong dependence between the properties of QD-associated small ligands and modes of uptake/elimination in human cells.