A Low Molecular Weight Hyaluronic Acid Derivative Accelerates Excisional Wound Healing by Modulating Pro-Inflammation, Promoting Epithelialization and Neovascularization, and Remodeling Collagen.

Recent knowledge of the cellular and molecular mechanisms underlying cutaneous wound healing has advanced the development of medical products. However, patients still suffer from the failure of current treatments, due to the complexity of healing process and thus novel therapeutic approaches are urgently needed. Previously, our laboratories produced a range of low molecular weight hyaluronic acid (LMW-HA) fragments, where a proportion of the glucosamine moieties were chemically N-acyl substituted. Specifically, N-butyrylation results in anti-inflammatory properties in a macrophage system, and we demonstrate the importance of N-acyl substituents in modulating the inflammatory response of LMW-HA. We have set up an inter-institutional collaborative program to examine the biomedical applications of the N-butyrylated LMW-HA (BHA). In this study, the potentials of BHA for dermal healing are assessed in vitro and in vivo. Consequently, BHA significantly promotes dermal healing relative to a commercial wound care product. By contrast, the "parent" partially de-acetylated LMW-HA (DHA) and the re-acetylated DHA (AHA) significantly delays wound closure, demonstrating the specificity of this N-acylation of LMW-HA in wound healing. Mechanistic studies reveal that the BHA-mediated therapeutic effect is achieved by targeting three phases of wound healing (i.e., inflammation, proliferation and maturation), demonstrating the significant potential of BHA for clinical translation in cutaneous wound healing.

Docetaxel-loaded human serum albumin (HSA) nanoparticles: synthesis, characterization, and evaluation.

BACKGROUND: Docetaxel (DTX) is an anticancer drug that is currently formulated with polysorbate 80 and ethanol (50:50, v/v) in clinical use. Unfortunately, this formulation causes hypersensitivity reactions, leading to severe side-effects, which have been primarily attributed to polysorbate 80. METHODS: In this study, a DTX-loaded human serum albumin (HSA) nanoparticle (DTX-NP) was designed to overcome the hypersensitivity reactions that are induced by polysorbate 80. The methods of preparing the DTX-NPs have been optimized based on factors including the drug-to-HSA weight ratio, the duration of HSA incubation, and the choice of using a stabilizer. Synthesized DTX-NPs were characterized with regard to their particle diameters, drug loading capacities, and drug release kinetics. The morphology of the DTX-NPs was observed via scanning electron microscopy (SEM) and the successful preparation of DTX-NPs was confirmed via differential scanning calorimetry (DSC). The cytotoxicity and cellular uptake of DTX-NPs were investigated in the non-small cell lung cancer cell line A549 and the maximum tolerated dose (MTD) of DTX-NPs was evaluated via investigations with BALB/c mice. RESULTS: The study showed that the loading capacity and the encapsulation efficiency of DTX-NPs prepared under the optimal conditions was 11.2 wt% and 63.1 wt%, respectively and the mean diameter was less than 200 nm, resulting in higher permeability and controlled release. Similar cytotoxicity against A549 cells was exhibited by the DTX-NPs in comparison to DTX alone while higher maximum tolerated dose (MTD) with the DTX-NPs (75 mg/kg) than with DTX (30 mg/kg) was demonstrated in mice, suggesting that the DTX-NPs prepared with HSA yielded similar anti-tumor activity but were accompanied by less systemic toxicity than solvent formulated DTX. CONCLUSIONS: DTX-NPs warrant further investigation and are promising candidates for clinical applications.

Antitumor effect of a liposome-encapsulated ß1,4-galactosyltransferase inhibitor.

Galactosyltransferases are a family of enzymes responsible for the synthesis of glycan chains which are involved in cell proliferation, adhesion and apoptosis. A recently synthesized galactosyltransferase inhibitor, 2-naphthyl 2-butanamido-2-deoxy-1-thio-ß-D-glucopyranoside (612), has been found to selectively inhibit ß1,4-galactosyltransferase over ß1,3-galactosyltransferase and, therefore, has potential to suppress the synthesis of cancer associated epitopes. However, the application of this inhibitory activity in biological systems remains unknown. In this study, 612 was introduced into a cationic liposome (LP) delivery system, and the anti-proliferative effects of both free and the LP-incorporated 612 (612-LP) were investigated in A549 lung cancer cells, which actively express anionic sialic acid moieties on the surfaces of cells. The anti-proliferative effects were evaluated via MTT assays. The results revealed that free 612 and empty LP impose neither anti-proliferative nor apoptotic effects on cancer cells at low doses, whereas the 612-LP system inhibited cancer cell growth at a concentration as low as 0.1 µg/mL after 3 days of incubation, suggesting that this formulation enabled efficient delivery of 612 into cells and promoted the anti-proliferative activity of 612 against cancer cells. Therefore, this highly specific inhibitor 612 has the potential for development as an effective anti-cancer agent and merits further investigation.