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Nanoscale Horizons Jun 2024Establishing scalable nanomaterials synthesis protocols remains a bottleneck towards their commercialisation and, thus, a topic of intense research and development....
Establishing scalable nanomaterials synthesis protocols remains a bottleneck towards their commercialisation and, thus, a topic of intense research and development. Herein, we present an automated machine-learning microfluidic platform capable of synthesising optically active nanomaterials from target spectra originating from prior experience, theorised or published. Implementing unsupervised Bayesian optimisation with Gaussian processes reduces the optimisation time and the need for prior knowledge to initiate the process. Using PTFE tubing and connectors enables facile change in reactor design. Ultimately, the platform substitutes the labour-intensive trial-and-error synthesis and provides a pathway to standardisation and volume synthesis, slowing down the translation and commercialisation of high-quality nanomaterials. As a proof-of-concept, Ag nanoplates and Prussian-blue nanoparticle protocols were optimised and validated for volume production.
PubMed: 38887909
DOI: 10.1039/d4nh00174e -
International Journal of Nanomedicine 2024Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is...
INTRODUCTION
Diabetes mellitus is frequently associated with foot ulcers, which pose significant health risks and complications. Impaired wound healing in diabetic patients is attributed to multiple factors, including hyperglycemia, neuropathy, chronic inflammation, oxidative damage, and decreased vascularization.
RATIONALE
To address these challenges, this project aims to develop bioactive, fast-dissolving nanofiber dressings composed of polyvinylpyrrolidone loaded with a combination of an antibiotic (moxifloxacin or fusidic acid) and anti-inflammatory drug (pirfenidone) using electrospinning technique to prevent the bacterial growth, reduce inflammation, and expedite wound healing in diabetic wounds.
RESULTS
The fabricated drug-loaded fibers exhibited diameters of 443 ± 67 nm for moxifloxacin/pirfenidone nanofibers and 488 ± 92 nm for fusidic acid/pirfenidone nanofibers. The encapsulation efficiency, drug loading and drug release studies for the moxifloxacin/pirfenidone nanofibers were found to be 70 ± 3% and 20 ± 1 µg/mg, respectively, for moxifloxacin, and 96 ± 6% and 28 ± 2 µg/mg, respectively, for pirfenidone, with a complete release of both drugs within 24 hours, whereas the fusidic acid/pirfenidone nanofibers were found to be 95 ± 6% and 28 ± 2 µg/mg, respectively, for fusidic acid and 102 ± 5% and 30 ± 2 µg/mg, respectively, for pirfenidone, with a release rate of 66% for fusidic acid and 80%, for pirfenidone after 24 hours. The efficacy of the prepared nanofiber formulations in accelerating wound healing was evaluated using an induced diabetic rat model. All tested formulations showed an earlier complete closure of the wound compared to the controls, which was also supported by the histopathological assessment. Notably, the combination of fusidic acid and pirfenidone nanofibers demonstrated wound healing acceleration on day 8, earlier than all tested groups.
CONCLUSION
These findings highlight the potential of the drug-loaded nanofibrous system as a promising medicated wound dressing for diabetic foot applications.
Topics: Diabetic Foot; Nanofibers; Animals; Moxifloxacin; Wound Healing; Bandages; Anti-Bacterial Agents; Pyridones; Fusidic Acid; Drug Liberation; Rats; Male; Diabetes Mellitus, Experimental; Povidone; Rats, Sprague-Dawley
PubMed: 38882541
DOI: 10.2147/IJN.S460467 -
Carbohydrate Polymers Oct 2024Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a...
Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a pH-responsive CMCS/PVP/TA (CPT) multifunctional hydrogel dressing by embedding the natural plant extract TA as a nonantibiotic and cross-linking agent in carboxymethyl chitosan (CMCS) and polyvinylpyrrolidone (PVP) to prompt wound healing. The CPT hydrogel demonstrated excellent self-healing, self-adaptive, and adhesion properties to match different wound requirements. Importantly, this hydrogel showed pH sensitivity and exhibited good activity against resistant bacteria and antioxidant activity by releasing TA in case of bacterial infection (alkaline). Furthermore, the CPT hydrogel exhibited coagulant ability and could rapidly stop bleeding within 30 s. The biocompatible hydrogel effectively accelerated wound healing in a full-thickness skin defect model by thickening granulation tissue, increasing collagen deposition, vascular proliferation, and M2-type macrophage polarization. In conclusion, this study demonstrates that multifunctional CPT hydrogel offers a candidate material with potential applications for infected skin wound healing.
Topics: Chitosan; Wound Healing; Hydrogels; Animals; Hydrogen-Ion Concentration; Mice; Bandages; Anti-Bacterial Agents; Povidone; Male; Staphylococcus aureus; Biocompatible Materials; Skin
PubMed: 38876718
DOI: 10.1016/j.carbpol.2024.122348 -
Nature Communications Jun 2024Generating 3D bone cell networks in vitro that mimic the dynamic process during early bone formation remains challenging. Here, we report a synthetic biodegradable...
Generating 3D bone cell networks in vitro that mimic the dynamic process during early bone formation remains challenging. Here, we report a synthetic biodegradable microporous hydrogel for efficient formation of 3D networks from human primary cells, analysis of cell-secreted extracellular matrix (ECM) and microfluidic integration. Using polymerization-induced phase separation, we demonstrate dynamic in situ formation of microporosity (5-20 µm) within matrix metalloproteinase-degradable polyethylene glycol hydrogels in the presence of living cells. Pore formation is triggered by thiol-Michael-addition crosslinking of a viscous precursor solution supplemented with hyaluronic acid and dextran. The resulting microporous architecture can be fine-tuned by adjusting the concentration and molecular weight of dextran. After encapsulation in microporous hydrogels, human mesenchymal stromal cells and osteoblasts spread rapidly and form 3D networks within 24 hours. We demonstrate that matrix degradability controls cell-matrix remodeling, osteogenic differentiation, and deposition of ECM proteins such as collagen. Finally, we report microfluidic integration and proof-of-concept osteogenic differentiation of 3D cell networks under perfusion on chip. Altogether, this work introduces a synthetic microporous hydrogel to efficiently differentiate 3D human bone cell networks, facilitating future in vitro studies on early bone development.
Topics: Humans; Hydrogels; Mesenchymal Stem Cells; Osteogenesis; Cell Differentiation; Osteoblasts; Extracellular Matrix; Porosity; Cell Culture Techniques, Three Dimensional; Polyethylene Glycols; Tissue Engineering; Hyaluronic Acid; Cells, Cultured; Tissue Scaffolds; Dextrans
PubMed: 38871693
DOI: 10.1038/s41467-024-49280-3 -
BMC Veterinary Research Jun 2024Antimicrobial resistance (AMR) is nowadays a major emerging challenge for public health worldwide. The over- and misuse of antibiotics, including those for cell culture,...
BACKGROUND
Antimicrobial resistance (AMR) is nowadays a major emerging challenge for public health worldwide. The over- and misuse of antibiotics, including those for cell culture, are promoting AMR while also encouraging the research and employment of alternative drugs. The addition of antibiotics to the cell media is strongly recommended in sperm preservation, being gentamicin the most used for boar semen. Because of its continued use, several bacterial strains present in boar semen have developed resistance to this antibiotic. Antimicrobial peptides and proteins (AMPPs) are promising candidates as alternative antibiotics because their mechanism of action is less likely to promote AMR. In the present study, we tested two AMPPs (lysozyme and nisin; 50 and 500 µg/mL) as possible substitutes of gentamicin for boar semen preservation up to 48 h of storage.
RESULTS
We found that both AMPPs improved sperm plasma membrane and acrosome integrity during semen storage. The highest concentration tested for lysozyme also kept the remaining sperm parameters unaltered, at 48 h of semen storage, and reduced the bacterial load at comparable levels of the samples supplemented with gentamicin (p > 0.05). On the other hand, while nisin (500 µg/mL) reduced the total Enterobacteriaceae counts, it also decreased the rapid and progressive sperm population and the seminal oxidation-reduction potential (p < 0.05).
CONCLUSIONS
The protective effect of lysozyme on sperm function together with its antimicrobial activity and inborn presence in body fluids, including semen and cervical mucus, makes this enzyme a promising antimicrobial agent for boar semen preservation.
Topics: Animals; Semen Preservation; Male; Anti-Bacterial Agents; Swine; Muramidase; Nisin; Semen; Spermatozoa; Antimicrobial Peptides; Cell Membrane; Gentamicins; Acrosome
PubMed: 38867200
DOI: 10.1186/s12917-024-04105-9 -
International Journal of Nanomedicine 2024The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to...
BACKGROUND
The healing of burn wounds is a complicated physiological process that involves several stages, including haemostasis, inflammation, proliferation, and remodelling to rebuild the skin and subcutaneous tissue integrity. Recent advancements in nanomaterials, especially nanofibers, have opened a new way for efficient healing of wounds due to burning or other injuries.
METHODS
This study aims to develop and characterize collagen-decorated, bilayered electrospun nanofibrous mats composed of PVP and PVA loaded with Resveratrol (RSV) and Ampicillin (AMP) to accelerate burn wound healing and tissue repair.
RESULTS
Nanofibers with smooth surfaces and web-like structures with diameters ranging from 200 to 400 nm were successfully produced by electrospinning. These fibres exhibited excellent in vitro properties, including the ability to absorb wound exudates and undergo biodegradation over a two-week period. Additionally, these nanofibers demonstrated sustained and controlled release of encapsulated Resveratrol (RSV) and Ampicillin (AMP) through in vitro release studies. The zone of inhibition (ZOI) of PVP-PVA-RSV-AMP nanofibers against ( and () was found 31±0.09 mm and 12±0.03, respectively, which was significantly higher as compared to positive control. Similarly, the biofilm study confirmed the significant reduction in the formation of biofilms in nanofiber-treated group against both and . X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis proved the encapsulation of RSV and AMP successfully into nanofibers and their compatibility. Haemolysis assay (%) showed no significant haemolysis (less than 5%) in nanofiber-treated groups, confirmed their cytocompatibility with red blood cells (RBCs). Cell viability assay and cell adhesion on HaCaT cells showed increased cell proliferation, indicating its biocompatibility as well as non-toxic properties. Results of the in-vivo experiments on a burn wound model demonstrated potential burn wound healing in rats confirmed by H&E-stained images and also improved the collagen synthesis in nanofibers-treated groups evidenced by Masson-trichrome staining. The ELISA assay clearly indicated the efficient downregulation of TNF-alpha and IL-6 inflammatory biomarkers after treatment with nanofibers on day 10.
CONCLUSION
The RSV and AMP-loaded nanofiber mats, developed in this study, expedite burn wound healing through their multifaceted approach.
Topics: Resveratrol; Nanofibers; Burns; Wound Healing; Animals; Collagen; Povidone; Staphylococcus aureus; Polyvinyl Alcohol; Humans; Escherichia coli; Ampicillin; Anti-Bacterial Agents; Rats; Biofilms; Male
PubMed: 38863647
DOI: 10.2147/IJN.S464046 -
AAPS PharmSciTech Jun 2024Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic...
Inclusion complexes require higher concentration of Beta cyclodextrins (βCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (K) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a βCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and β-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.
Topics: beta-Cyclodextrins; Chemistry, Pharmaceutical; Cyclodextrins; Drug Liberation; Excipients; Molecular Weight; Pilot Projects; Povidone; Solubility; Thermodynamics
PubMed: 38862663
DOI: 10.1208/s12249-024-02845-3 -
International Journal of Nanomedicine 2024Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor...
INTRODUCTION
Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.
METHODS
HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.
RESULTS
Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.
CONCLUSION
HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.
Topics: Animals; Nanoparticles; Hydroxyethyl Starch Derivatives; Luteolin; Mice; Caco-2 Cells; Hyperuricemia; Humans; Male; Particle Size; Disease Models, Animal; Solubility; Uric Acid; Biological Availability; Administration, Oral; Drug Stability
PubMed: 38859954
DOI: 10.2147/IJN.S464948 -
Journal of Food Science Jul 2024Polyvinylpolypyrrolidone (PVPP) is a synthetic, insoluble polymer that can be added to white wines to improve the chemical stability of the final product by...
Polyvinylpolypyrrolidone (PVPP) is a synthetic, insoluble polymer that can be added to white wines to improve the chemical stability of the final product by precipitating unstable low molecular weight phenolic compounds responsible for visual defects and undesirable flavor characteristics (e.g., excessive bitterness and/or astringency). The objective of this study was to characterize the effects of PVPP on the quality characteristics of Viognier wine when added pre- or post-fermentation as compared to an untreated control wine. Both PVPP-treated wines contained significantly lower concentrations of monomeric phenolics and browning pigments than the control wine (p ≤ 0.05). The addition of PVPP prior to fermentation conferred protection against oxidation of the wine as measured by acetaldehyde concentration (p ≤ 0.05). Analysis of the volatile aroma profile of each wine by headspace solid phase microextraction gas chromatographymass spectrometry (HS-SPME-GC-MS) revealed that the overarching aroma profiles of the PVPP-treated wines were significantly different from the control wine, but there was no difference between wines treated with PVPP pre-fermentation versus those treated post-fermentation. Specifically, statistically significant differences were observed in 9 of the 22 quantified aroma compounds, including those notably associated with the "stone fruit" aroma of Viognier. A negative correlation was identified between aroma compound concentration removal and the hydrophobicity of each compound, suggesting that the observed differences in aroma may be due to adsorption of aroma compounds by PVPP. The findings from this study present risks and benefits to wine quality upon treatment with PVPP at commercially recommended levels, and provide potentially valuable information for industrial wine producers.
Topics: Wine; Povidone; Odorants; Gas Chromatography-Mass Spectrometry; Fermentation; Volatile Organic Compounds; Phenols; Solid Phase Microextraction; Taste; Food Handling
PubMed: 38858776
DOI: 10.1111/1750-3841.17141 -
The Journal of Physical Chemistry... Jun 2024The effects of two macromolecular cosolutes, specifically the polysaccharide dextran-20 and the protein lysozyme, on the aggregation kinetics of a pathogenic huntingtin...
The effects of two macromolecular cosolutes, specifically the polysaccharide dextran-20 and the protein lysozyme, on the aggregation kinetics of a pathogenic huntingtin exon-1 protein (hht) with a 35 polyglutamine repeat, httQ, are described. A unified kinetic model that establishes a direct connection between reversible tetramerization occurring on the microsecond time scale and irreversible fibril formation on a time scale of hours/days forms the basis for quantitative analysis of httQ aggregation, monitored by measuring cross-peak intensities in a series of 2D H-N NMR correlation spectra acquired during the course of aggregation. The primary effects of the two cosolutes are associated with shifts in the prenucleation tetramerization equilibrium resulting in substantial changes in concentration of "preformed" httQ tetramers. Similar effects of the two cosolutes on the tetramerization equilibrium observed for a shorter, nonaggregating huntingtin variant with a 7-glutamine repeat, httQ, lend confidence to the conclusions drawn from the fits to the httQ aggregation kinetics.
Topics: Huntingtin Protein; Kinetics; Muramidase; Humans; Dextrans; Peptides; Nuclear Magnetic Resonance, Biomolecular; Protein Aggregates; Macromolecular Substances; Protein Multimerization; Magnetic Resonance Spectroscopy
PubMed: 38857530
DOI: 10.1021/acs.jpclett.4c01410