Polymeric scaffold integrated with nanovesicle-entrapped curcuminoids for enhanced therapeutic efficacy.

Aim: Polymeric scaffolds were developed fortified with nanovesicle-encapsulated individual curcumin (CUR) and tetrahydrocurcumin (THC) for improved therapeutic efficacy due to their low stability and efficacy in native form. Method: Nanovesicle-encapsulated individual CUR and THC were fabricated using thin-film hydration techniques and characterized. Results & conclusion: CUR/THC in native and vesicle-encapsulated form demonstrated diminished LPS-instigate nitric oxide (NO) levels in macrophage cells in a concentration-dependent demeanor. However, vesicle-encapsulated CUR/THC inhibited NO production at lower concentrations, compared with the native CUR/THC form. Furthermore, the scaffold fortified with vesicle-encapsulated CUR/THC demonstrated improved physical properties with excellent antioxidant, biocompatibility, and human keratinocyte cell proliferation ability. The results recommended that nanovesicle-encapsulated THC can be retained as a potential substitute for CUR with improved therapeutic efficacy.

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Poly (vinyl alcohol)-gelatin-sericin copolymerized film fortified with vesicle-entrapped demethoxycurcumin/bisdemethoxycurcumin for improved stability, antibacterial, anti-inflammatory, and skin tissue regeneration.

Vesicle delivery carriers, used to stabilize hydrophobic drugs, are characterized by the propensity to aggregate, and fuse, limiting its applications. Fortifying vesicle-entrapped drugs within a biodegradable polymeric film constitutes a promising solution. In this study, biodegradable poly (vinyl alcohol) copolymerized with gelatin-sericin film and integrated alongside vesicle-entrapped demethoxycurcumin (DMC) or bisdemethoxycurcumin (BDMC) was developed, extensively characterized for improve efficacy, and compared. Vesicle-entrapped DMC or BDMC was spherical in shape with no changes in size, zeta-potential, and morphology after storing at 4 °C for 30 days. Antibacterial activity of vesicle-entrapped DMC formulations against Acinetobacter baumannii and Staphylococcus epidermidis was more effective than that of its free form. DMC and BDMC demonstrated dose dependent reduction in lipopolysaccharides (LPS)-induced nitric oxide (NO) levels either in free or in entrapped form. Moreover, vesicle-entrapped DMC/BDMC suppressed NO production at lower concentrations, compared with that of their free form and significantly improved the viability of RAW264.7 and HaCaT cells. Furthermore, functionalized film with vesicle-entrapped DMC/BDMC demonstrated excellent radical scavenging, biocompatibility, and cell migration efficacy. Thus, incorporating vesicle, entrapped DMC/BDMC within biodegradable polymeric film may comprised a promising strategy for improving stability, wound healing, and inflammation attenuation efficacy.

Poly (vinyl alcohol) copolymerized with xanthan gum/hypromellose/sodium carboxymethyl cellulose dermal dressings functionalized with biogenic nanostructured materials for antibacterial and wound healing application.

Effective treatment of infected wounds requires a comprehensive wound dressing with a combination of antibacterial, antioxidative, and anti-inflammatory effects. Biodegradable wound dressings incorporating nanostructured material were developed using polyvinyl alcohol with xanthan gum, hypromellose, or sodium carboxymethyl cellulose and extensively evaluated for antibacterial and wound healing efficacy. Synthesized silver nanoparticles and wound dressings displayed λmax at 420 nm with zeta potential ≈ - 35 mV. Significant growth inhibition with >99 % reduction in CFU/ml (p < 0.05) against important wound pathogens including Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were observed. Within 1 h of treatment, hypromellose nanocomposite demonstrated excellent bactericidal effects with a 99.9 % of reduction in growth. In addition, wound dressings demonstrated inhibitory activities against free radical scavengers. Wound dressings demonstrated a significant reduction in the inflammatory response in RAW 264.7 macrophages (p < 0.001). Ex-vivo diffusion demonstrated zero-order release and steady-state flux between 0.1571-0.2295 µg/ml/cm2h with 0.124-0.144 permeability coefficient after 10 h. Usage in animals further confirmed that the hypromellose nanocomposite accelerated the wound healing process with biocompatibility. The results suggested that hybrid biodegradable dressings can be effectively applied to treat infected wounds and attenuate inflammatory responses.

Association Between Types of Carbapenemase and Clinical Outcomes of Infection Due to Carbapenem Resistance Enterobacterales.

Purpose: Compared with non-carbapenemase producing carbapenem-resistant Enterobacterales (non-CP-CRE), carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) are associated with considerable mortality. However, given that the patients are treated with various therapeutic options, it remains unclear whether differences in types of carbapenemase genes yield different mortality rates. Therefore, this study aims to identify carbapenemase genes and identify whether clinical outcomes differ according to the prevalence of genotype and phenotype of carbapenemase among Enterobacterales clinical isolated. Patients and Methods: A retrospective cohort study was performed to determine whether types of carbapenemase genes have an impact on clinical outcomes. Carbapenem-resistant clinical isolates were collected at a tertiary care university hospital in Songkhla, Thailand, between June 2018 and February 2020. Demographic and microbiological data such as antimicrobial susceptibility, carbapenemase genes, and overall mortality were evaluated. Results: A total of 121 Enterobacterales clinical isolated were evaluated. The bla NDM-1 gene was detected in 44% of the isolates, followed by bla OXA-48 (28%) and bla NDM-1/OXA-48 (28%). NDM-1- or NDM-1/OXA-48- producing isolates were more likely to require meropenem MICs of ≥16 mg/L, while OXA-48-producing isolates were more likely to require meropenem MICs of <16 mg/L. The patients with NDM-1 or NDM-1/OXA-48 had a higher 14 days mortality rate than those with OXA-48 after treating with carbapenem-containing regimens (P-value 0.001) or colistin-containing regimens (P-value < 0.001). Conclusion: Our findings suggest that the mortality for CP-CRE infection in patients with NDM-1 or NDM-1/OXA-48 was higher than the mortality in those with OXA-48, which It seems that the type of carbapenemase gene may affect meropenem MIC levels. Hence, in treatment decisions involving the use of either carbapenem-containing regiment or colistin-containing regiment in patients with CP-CRE infection, especially those in the NDM-1 and NDM-1/OXA-48 groups, the patient symptoms should be closely monitored.

Rhodomyrtone Accumulates in Bacterial Cell Wall and Cell Membrane and Inhibits the Synthesis of Multiple Cellular Macromolecules in Epidemic Methicillin-Resistant Staphylococcus aureus.

As the burden of antibacterial resistance worsens and treatment options become narrower, rhodomyrtone-a novel natural antibiotic agent with a new antibacterial mechanism-could replace existing antibiotics for the treatment of infections caused by multi-drug resistant Gram-positive bacteria. In this study, rhodomyrtone was detected within the cell by means of an easy an inexpensive method. The antibacterial effects of rhodomyrtone were investigated on epidemic methicillin-resistant Staphylococcus aureus. Thin-layer chromatography demonstrated the entrapment and accumulation of rhodomyrtone within the bacterial cell wall and cell membrane. The incorporation of radiolabelled precursors revealed that rhodomyrtone inhibited the synthesis of macromolecules including DNA, RNA, proteins, the cell wall, and lipids. Following the treatment with rhodomyrtone at MIC (0.5-1 µg/mL), the synthesis of all macromolecules was significantly inhibited (p ≤ 0.05) after 4 h. Inhibition of macromolecule synthesis was demonstrated after 30 min at a higher concentration of rhodomyrtone (4× MIC), comparable to standard inhibitor compounds. In contrast, rhodomyrtone did not affect lipase activity in staphylococci-both epidemic methicillin-resistant S. aureus and S. aureus ATCC 29213. Interfering with the synthesis of multiple macromolecules is thought to be one of the antibacterial mechanisms of rhodomyrtone.

Evaluation of the Synergistic Antibacterial Effects of Fosfomycin in Combination with Selected Antibiotics against Carbapenem-Resistant Acinetobacter baumannii.

The spread of multi-drug resistant (MDR) pathogens and the lagging pace in the development of novel chemotherapeutic agents warrant the use of combination therapy as a reliable, cost-effective interim option. In this study, the synergistic effects of fosfomycin in combination with other antibiotics were assessed. Of the 193 isolates, 90.6% were non-susceptible to fosfomycin, with minimum inhibitory concentrations (MICs) of ≥128 µg/mL. Antibacterial evaluation of fosfomycin-resistant isolates indicated multi-drug resistance to various antibiotic classes. Combinations of fosfomycin with 12 commonly used antibiotics synergistically inhibited most fosfomycin-resistant isolates. The fractional inhibitory concentration index indicated that combining fosfomycin with either aminoglycosides, glycylcyclines, fluoroquinolones, or colistin resulted in 2- to 16-fold reduction in the MIC of fosfomycin. Time-kill kinetics further confirmed the synergistic bactericidal effects of fosfomycin in combination with either amikacin, gentamicin, tobramycin, minocycline, tigecycline, or colistin, with more than 99.9% reduction in bacterial cells. Fosfomycin-based combination therapy might serve as an alternative option for the treatment of MDR A. baumannii. Further steps including in vivo efficacy and toxicity in experimental models of infection are required prior to clinical applications.

Potential of antimicrobial topical gel with synthesized biogenic silver nanoparticle using Rhodomyrtus tomentosa leaf extract and silk sericin.

OBJECTIVE: Silver nanoparticles synthesized using Rhodomyrtus tomentosa leaf extract and silk sericin were used to functionalize carbopol 940 gel for topical applications. RESULTS: UV-vis spectra presented surface plasmon resonance at 426 nm, transmission electron microscopy revealed that nanoparticles were spherical with an average size of 25-50 nm. X-ray diffraction presented crystalline silver nanoparticles with zeta potential of ≈ - 30 mV. FTIR spectra showed a reduction of silver nitrate indicated by the shift in -OH at 2958 cm-1. The silver nanoparticle demonstrated broad-spectrum antimicrobial activity against Gram-positive, Gram-negative and fungi with MIC ranging between 0.26 and 2.10 µg mL-1, respectively. MIC of hydrogel ranged between 1.05-2.10 µg mL-1 with cell viability of 89%. Spreadability and extrudability of gel were 9.3 ± 0.85 s and 19.85 ± 0.03%, respectively with first order of fickian diffusion. CONCLUSIONS: The silver nanoparticle gel exhibited an effective antimicrobial property, hence can be exploited for topical applications.

Characterization of a novel, co-processed bio-based polymer, and its effect on mucoadhesive strength.

In this study, a biological macromolecule obtained from seeds of Manilkara zapota was co-processed with hypromellose (cop-MPH)/sodium carboxymethylcellulose (cop-MPN)/polyvinylpyrrolidone (cop-MPP) in a 1:1 ratio and characterized for powder and mucoadhesive properties. The semi-crystalline nature of co-processed excipients and physical interaction between the component molecules were confirmed by X-ray diffraction and infrared spectroscopy analysis. The morphological study by scanning electron and atomic force microscopy showed spherical and polygonal-shaped particles with predominant smooth surfaces. Thermogravimetric analysis revealed thermal stability to a temperature of 200 °C followed by depolymerization. Zeta potential measurements showed that cop-MPP was anionic, whereas cop-MPH and MPN were non-ionic. Texture analysis revealed that work of adhesion (mN·s) for both cop-MPH (390 ± 0.0018) and MPN (304 ± 0.0024) enhanced the mucoadhesion compared with the un-processed hypromellose (300 ± 0.0019) and sodium carboxymethylcellulose (280 ± 0.0012), whereas cop-MPP (240 ± 0.0028) showed mucoadhesion similar to un-processed polyvinylpyrrolidone (250 ± 0.0022). In addition, the swelling studies showed enhancement in water absorbance for all co-processed excipients. Cytotoxicity against human cells revealed >99% of cell viability. These findings demonstrate that the co-processed biological macromolecule extracted from M. zapota seed could be further explored as an effective alternative drug delivery excipient for pharmaceutical applications.