betadex and Burns

Hydrogels formed through reversible supramolecular interactions may attain self-healing in the in situ environment. However, the low grafting degree of functional groups and steric hindrance effect of polymer backbones significantly reduced the self-healing efficacy and kinetics. To overcome these deficiencies, we designed a novel hydrogel via non-covalent host-guest interaction between β-cyclodextrin modified hyaluronic acid (HA-CD) and adamantane modified 4-arm-PEG (4-arm-PEG-Ad). The multi-armed monomer enabled to increase the number of functional groups and avoid steric hindrance effects, offering more efficient host-guest interaction. The insoluble dexamethasone could be loaded in the β-CDs' hydrophobic cavities. The designed hydrogels exhibited excellent self-healing properties. The mechanical strengths, swelling rate and release of dexamethasone could be adjusted by adding 4-arm-PEG-Ad. The novel hydrogels significantly improved the therapeutic effect of the dexamethasone in burn wound healing. Herein, these hydrogels had great potential for direct, convenient, and efficient delivery of hydrophobic drugs and improved their therapeutic effects.

Topics: 3T3 Cells; Adamantane; Animals; Anti-Inflammatory Agents; beta-Cyclodextrins; Burns; Cell Survival; Cross-Linking Reagents; Dexamethasone; Drug Delivery Systems; Drug Liberation; Hyaluronic Acid; Hydrogels; Hydrophobic and Hydrophilic Interactions; Mice; Polyethylene Glycols; Rats, Sprague-Dawley; Wound Healing

Excessive inflammation and reduced angiogenesis are two major obstacles in burn wound healing and skin regeneration. Here we report the fabrication and application of a sophisticated hydrogel from chemically modified hyaluronic acid (HA), dextran (Dex), and β-cyclodextrin (β-CD) integrating resveratrol (Res) and vascular endothelial growth factor (VEGF) plasmid as the anti-inflammatory and pro-angiogenic components for burn wounds. Firstly, covalent alterations were conducted to obtain methacrylic acid anhydride modified HA (HAMA), N-hydroxyethylacrylamide (HEAA) modified Dex (Dex-HEAA), and poly(ethylene glycol) methyl acrylate (526) modified β-CD (526-β-CD), respectively. Secondly, anti-inflammatory substance Res was embedded into the lipophilic central cavity of 526-β-CD to achieve a complex of 526-β-CD-Res. Then hydrogels with different HAMA, Dex-HEAA, and 526-β-CD-Res ratios were generated via UV irradiation. Lastly, plasmid DNA encoded with vascular endothelial growth factor (pDNA-VEGF) conjugating with polyethylenimine was loaded into the hydrogel scaffold. Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds. STATEMENT OF SIGNIFICANCE: Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds.

Topics: 3T3 Cells; Animals; Anti-Inflammatory Agents; beta-Cyclodextrins; Biocompatible Materials; Burns; Dextrans; Disease Models, Animal; DNA; Human Umbilical Vein Endothelial Cells; Humans; Hyaluronic Acid; Hydrogels; Interleukin-1beta; Male; Mice; Neovascularization, Physiologic; Plasmids; Rats, Sprague-Dawley; Resveratrol; RNA, Messenger; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Wound Healing

The present study was designed to determine the role of curcumin-β-cyclodextrin-loaded sponge on burn wound healing in rats. Curcumin-β-cyclodextrin complex was prepared by the solvent evaporation encapsulation method. Molecular inclusion complex of curcumin-β-cyclodextrin was incorporated into gelatin sponge. The developed sponge was characterized for drug entrapment, drug release and morphology. The biological activity of optimized formulation was determined on burn wounds which were made on rats. The burn wound healing efficacy was analyzed through physical and histological changes observed at the wound sites. There was a significant decrease in rate of wound contraction in experimental groups then the control group. Curcumin-β-cyclodextrin-loaded sponge treated wound was found to heal in rate comparable to marketed formulation with no sign of adverse consequence. The result clearly substantiates the beneficial effects of curcumin-β-cyclodextrin-loaded sponge in the acceleration of wound healing.

Topics: Animals; beta-Cyclodextrins; Burns; Chemistry, Pharmaceutical; Curcumin; Drug Delivery Systems; Porifera; Rats; Rats, Wistar; Wound Healing