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1.
J Mater Chem B ; 7(42): 6592-6603, 2019 11 14.
Article in English | MEDLINE | ID: mdl-31589221

ABSTRACT

Management of infected wounds is one of the most costly procedures in the health care sector. Burn wounds are of significant importance due to the high infection risk that can possibly lead to severe consequences such as sepsis. Because antibiotic wound treatments have caused increasing antibiotic resistance in bacteria, there is currently a strong need for alternative strategies. Therefore, we developed new antimicrobial wound dressings consisting of pH-responsive human serum albumin/silk fibroin nanocapsules immobilized onto cotton/polyethylene terephthalate (PET) blends loaded with eugenol, which is an antimicrobial phenylpropanoid. Ultrasound-assisted production of eugenol-loaded nanocapsules resulted in particle sizes (hydrodynamic radii) between 319.73 ± 17.50 and 574.00 ± 92.76 nm and zeta potentials ranging from -10.39 ± 1.99 mV to -12.11 ± 0.59 mV. Because recent discoveries have indicated that the sweat glands contribute to wound reepithelialisation, release studies of eugenol were conducted in different artificial sweat formulas that varied in pH. Formulations containing 10% silk fibroin with lower degradation degree exhibited the highest release of 41% at pH 6.0. After immobilization, the functionalized cotton/PET blends were able to inhibit 81% of Staphylococcus aureus and 33% of Escherichia coli growth. Particle uniformity, silk fibroin concentration, and high surface-area-to-volume ratio of the produced nanocapsules were identified as the contributing factors leading to high antimicrobial activities against both strains. Therefore, the production of antimicrobial textiles using nanocapsules loaded with an active natural compound that will not contribute to antibiotic resistance is seen as a potential future alternative to commercially available antiseptic wound dressings.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cotton Fiber , Eugenol/pharmacology , Nanocapsules/chemistry , Polyethylene Terephthalates/chemistry , Smart Materials/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Bandages , Carboxylic Ester Hydrolases/chemistry , Cell Line , Cellulase/chemistry , Cotton Fiber/toxicity , Drug Delivery Systems , Drug Liberation , Escherichia coli/drug effects , Eugenol/chemistry , Eugenol/toxicity , Fibroins/chemistry , Fibroins/toxicity , Humans , Nanocapsules/toxicity , Polyethylene Terephthalates/toxicity , Serum Albumin, Human/chemistry , Serum Albumin, Human/toxicity , Smart Materials/chemistry , Smart Materials/toxicity , Staphylococcus aureus/drug effects
2.
Eur J Pharm Biopharm ; 133: 176-187, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30291964

ABSTRACT

Inflammation processes are associated with significant decreases in tissue or lysosomal pH from 7.4 to 4, a fact that argues for the application of pH-responsive drug delivery systems. However, for their design and optimization a full understanding of the release mechanism is crucial. In this study we investigated the pH-depending drug release mechanism and the influence of silk fibroin (SF) concentration and SF degradation degree of human serum albumin (HSA)-SF nanocapsules. Sonochemically produced nanocapsules were investigated regarding particle size, colloidal stability, protein encapsulation, thermal stability and drug loading properties. Particles of the monodisperse phase showed average hydrodynamic radii between 438 and 888 nm as measured by DLS and AFM and a zeta potential of -11.12 ±â€¯3.27 mV. Together with DSC results this indicated the successful production of stable nanocapsules. ATR-FTIR analysis demonstrated that SF had a positive effect on particle formation and stability due to induced beta-sheet formation and enhanced crosslinking. The pH-responsive release was found to depend on the SF concentration. In in-vitro release studies, HSA-SF nanocapsules composed of 50% SF showed an increased pH-responsive release for all tested model substances (Rhodamine B, Crystal Violet and Evans Blue) and methotrexate at the lowered pH of 4.5 to pH 5.4, while HSA capsules without SF did not show any pH-responsive drug release. Mechanistic studies using confocal laser scanning microscopy (CLSM) and small angle X-ray scattering (SAXS) analyses showed that increases in particle porosity and decreases in particle densities are directly linked to pH-responsive release properties. Therefore, the pH-responsive release mechanism was identified as diffusion controlled in a novel and unique approach by linking scattering results with in-vitro studies. Finally, cytotoxicity studies using the human monocytic THP-1 cell line indicated non-toxic behavior of the drug loaded nanocapsules when applied in a concentration of 62.5 µg mL-1. Based on the obtained release properties of HSA-SF nanocapsules formulations and the results of in-vitro MTT assays, formulations containing 50% SF showed the highest requirements arguing for future in vivo experiments and application in the treatment of inflammatory diseases.


Subject(s)
Fibroins/chemistry , Nanocapsules/chemistry , Serum Albumin, Human/chemistry , Silk/chemistry , Diffusion , Drug Compounding/methods , Drug Delivery Systems/methods , Drug Liberation/drug effects , Evans Blue/chemistry , Gentian Violet/chemistry , Humans , Hydrogen-Ion Concentration , Particle Size , Rhodamines/chemistry , Scattering, Small Angle , Surface Properties , X-Ray Diffraction/methods
3.
Biotechnol Bioeng ; 113(12): 2553-2560, 2016 12.
Article in English | MEDLINE | ID: mdl-27241438

ABSTRACT

There is a strong need for simple and fast diagnostic tools for the detection of wound infection. Immune system-derived enzymes like myeloperoxidase are efficient biomarkers for wound infection that emerge in the early stage infection process. In this study, 5-amino-2-methoxyphenol was functionalized with alkoxysilane to allow visual detection of MPO on carrier materials, for example, in test strips. Indeed, MPO activity was visually detectable in short time in wound background. Oxidation of the substrate was followed spectrophotometrically and proved via HPLC. LC-ESI TOF and NMR analyses unveiled the reaction mechanism and a dimeric reaction product responsible for the visualization of MPO activity. The substrate specificity and sensitivity toward MPO detection was proved and tests with infected wound fluids were successfully performed. The study demonstrates the suitability of the novel MPO substrate for the detection of wound infection and the covalent immobilization on diagnostic carrier materials. Biotechnol. Bioeng. 2016;113: 2553-2560. © 2016 Wiley Periodicals, Inc.


Subject(s)
Biomarkers/analysis , Colorimetry/methods , Guaiacol/chemistry , Peroxidase/analysis , Wound Infection/diagnosis , Wound Infection/metabolism , Adsorption , Biocompatible Materials/chemistry , Biosensing Techniques/methods , Humans , Reproducibility of Results , Sensitivity and Specificity
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