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1.
Acta Biomater ; 100: 142-157, 2019 12.
Article in English | MEDLINE | ID: mdl-31586728

ABSTRACT

To improve the efficacy of transdermal drug delivery systems, the physical and chemical properties of drugs need to be optimized to better penetrate into the stratum corneum and to better diffuse into the epidermis and dermis layers. Accordingly, dual-biological function ionic liquids composed of active pharmaceutical ingredients were synthesized, comprising both analgesic and anti-inflammatory properties, by combining a cation derived from lidocaine and anions derived from hydrophobic nonsteroidal anti-inflammatory drugs. Active pharmaceutical ingredient ionic liquids (API-ILs) were characterized through nuclear magnetic resonance, cytotoxicity assay, and water solubility assay. All properties were compared with those of the original drugs. By converting the analgesic and anti-inflammatory drugs into dual-function API-ILs, their water solubility increased up to 470-fold, without affecting their cytotoxic profile. These API-ILs were incorporated into a bilayer wound dressing composed of a hydrophobic polyvinylidene fluoride (PVDF) membrane to act as a drug reservoir and a biocompatible hyaluronic acid (HA) layer. The prepared bilayer wound dressing was characterized in terms of mechanical properties, membrane drug uptake and drug release behavior, and application in transdermal delivery, demonstrating to have desirable mechanical properties and improved release of API-ILs. The assessment of anti-inflammatory activity through the inhibition of LPS-induced production of nitric oxide and prostaglandin E2 by macrophages revealed that the prepared membranes containing API-ILs are as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assay confirmed improved the viability and adhesion of fibroblasts on PVDF/HA membranes. Finally, wound healing assay performed with fibroblasts showed that the bilayer membranes containing dual-function API-ILs are not detrimental to wound healing, while displaying increased and controlled drug delivery and dual therapeutic behavior. STATEMENT OF SIGNIFICANCE: This work shows the preparation and characterization of bilayer wound dressings comprising dual-biological function active pharmaceutical ingredients based on ionic liquids with improved and controlled drug release and dual therapeutic efficiency. By converting analgesic and anti-inflammatory drugs into ionic liquids, their water solubility increases up to 470-fold. The prepared bilayer wound dressing membranes have desirable mechanical properties and improved release of drugs. The prepared membranes comprising ionic liquids display anti-inflammatory activity as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assays show improved viability and adhesion of fibroblasts on PVDF/HA membranes, being thus of high relevance as effective transdermal drug delivery systems.


Subject(s)
Bandages , Drug Delivery Systems , Hyaluronic Acid/chemistry , Ionic Liquids/chemistry , Polyvinyls/chemistry , Wound Healing/drug effects , 3T3 Cells , Animals , Anti-Inflammatory Agents/pharmacology , Cell Adhesion/drug effects , Cell Survival/drug effects , Drug Liberation , Elastic Modulus , Mice , RAW 264.7 Cells , Solubility , Spectroscopy, Fourier Transform Infrared , Temperature , Tensile Strength , Water/chemistry
2.
Carbohydr Polym ; 222: 115033, 2019 Oct 15.
Article in English | MEDLINE | ID: mdl-31320054

ABSTRACT

Hyaluronic acid (HA), a naturally sourced polysaccharide, has shown remarkable effectiveness on wound healing, but its low mechanical strength and instability limits its frequent application in this field. In order to minimize this shortcoming, hyaluronic acid based wound dressings were blended with functionalized ZIF-8, which not only provides high mechanical strength, but also introduces antibacterial properties and promotes fibroblast migration and proliferation. To analyze physiochemical and biological characteristics of prepared wound dressings, tests including DLS, XRD, FTIR as well as antibacterial and cell adhesion assays were carried out. Results indicated that HA film modification boosted the Young's modulus from 138 to 176 K Pa, and reduced the water contact angle from 37.4 to 27.7 proving enhancement in hydrophilicity. Ameliorated antibacterial properties and better cell adhesion were also observed. Suitable cell viability was observed in samples with FZIF-8, since released Zn ions maintained within a safe concentration range.


Subject(s)
Anti-Bacterial Agents/pharmacology , Hyaluronic Acid/pharmacology , Metal-Organic Frameworks/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Cell Adhesion/drug effects , Cell Line , Elastic Modulus , Escherichia coli/drug effects , Hyaluronic Acid/chemistry , Imidazoles/chemistry , Metal-Organic Frameworks/chemistry , Mice , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Tensile Strength , Zinc/chemistry
3.
Mater Sci Eng C Mater Biol Appl ; 42: 443-50, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25063140

ABSTRACT

Polypropylene hollow fiber microporous membranes have been used in a wide range of applications, including blood oxygenator. The hydrophobic feature of the polypropylene surface causes membrane fouling. To minimize fouling, a modification consisting of three steps: surface activation in H2 and O2 plasma, membrane immersion in polyethylene glycol (PEG) and plasma graft polymerization was performed. The membranes were characterized by contact angle measurement, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), tensile test, scanning electron microscopy (SEM) and atomic force microscopy (AFM). Oxygen transfer of modified membranes was also tested. The stability of grafted PEG was measured in water and in phosphate buffer saline (PBS) at 37°C. Blood compatibility of modified surfaces was evaluated by the platelet adhesion method. Water contact angel reduction from 110° to 72° demonstrates the enhanced hydrophilicity, and XPS results verify the presence of oxygenated functional groups due to the peak existence in 286 eV as a result of PEG grafting. The results clearly indicate that plasma graft-polymerization of PEG is an effective way for antifouling improvement of polypropylene membranes. Also, the results show that oxygen transfer changes in PEG grafted membranes are not significant.


Subject(s)
Membranes, Artificial , Polyethylene Glycols/chemistry , Polypropylenes/chemistry , Surface Properties , Biocompatible Materials , Humans , Hydrophobic and Hydrophilic Interactions , Materials Testing , Oxygen/analysis , Oxygen/metabolism , Plasma Gases/chemistry , Platelet Adhesiveness/drug effects , Platelet-Rich Plasma/cytology , Polyethylene Glycols/toxicity , Polymerization , Polypropylenes/toxicity
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