Synthesis of high-performance antibacterial agent based on incorporated vancomycin into MOF-modified lignin nanocomposites.

The alarming rise in antibiotic resistance necessitates urgent action, particularly against the backdrop of resistant bacteria evolving to render conventional antibiotics less effective, leading to an increase in morbidity, mortality, and healthcare costs. Vancomycin-loaded Metal-Organic Framework (MOF) nanocomposites have emerged as a promising strategy in enhancing the eradication of pathogenic bacteria. This study introduces lignin as a novel synergistic agent in Vancomycin-loaded MOF (Lig-Van-MOF), which substantially enhances the antibacterial activity against drug-resistant bacteria. Lig-Van-MOF exhibits six-fold lower minimum inhibitory concentration (MICs) than free vancomycin and Van-MOF with a much higher antibacterial potential against sensitive and resistant strains of Staphylococcus aureus and Escherichia coli. Remarkably, it reduces biofilms of these strains by over 85 % in minimal biofilm inhibitory concentration (MBIC). Utilization of lignin to modify surface properties of MOFs improves their adhesion to bacterial membranes and boosts the local concentration of Reactive Oxygen Species (ROS) via unique synergistic mechanism. Additionally, lignin induces substantial cell deformation in treated bacterial cells. It confirms the superior bactericidal properties of Lig-Van-MOF against Staphylococcus species, underlining its significant potential as a bionanomaterial designed to combat antibiotic resistance effectively. This research paves the way for novel antibacterial platforms that optimize cost-efficiency and broaden microbial resistance management applications.

Microarray needles comprised of arginine-modified chitosan/PVA hydrogel for enhanced antibacterial and wound healing potential of curcumin.

Wound healing is a multifaceted and complex process that includes inflammation, hemostasis, remodeling, and granulation. Failures in any link may cause the healing process to be delayed. As a result, wound healing has always been a main research focus across the entire medical field, posing significant challenges and financial burdens. Hence, the current investigation focused on the design and development of arginine-modified chitosan/PVA hydrogel-based microneedles (MNs) as a curcumin (CUR) delivery system for improved wound healing and antibacterial activity. The substrate possesses exceptional swelling capabilities that allow tissue fluid from the wound to be absorbed, speeding up wound closure. The antibacterial activity of MNs was investigated against S. aureus and E. coli. The results revealed that the developed CUR-loaded MNs had increased antioxidant activity and sustained drug release behavior. Furthermore, after being loaded in the developed MNs, it revealed improved antibacterial activity of CUR. Wound healing potential was assessed by histopathological analysis and wound closure%. The observed results suggest that the CUR-loaded MNs greatly improved wound healing potential via tissue regeneration and collagen deposition, demonstrating the potential of developed MNs patches to be used as an effective carrier for wound healing in healthcare settings.

Improving curcumin bactericidal potential against multi-drug resistant bacteria via its loading in polydopamine coated zinc-based metal-organic frameworks.

Multi-drug resistant (MDR) bactearial strains have posed serious health issues, thus leading to a significant increase in mortality, morbidity, and the expensive treatment of infections. Metal-organic frameworks (MOFs), comprising metal ions and a variety of organic ligands, have been employed as an effective drug deliveryy vehicle due to their low toxicity, biodegradability, higher structural integrity and diverse surface functionalities. Polydopamine (PDA) is a versatile biocompatible polymer with several interesting properties, including the ability to adhere to biological surfaces. As a result, modifying drug delivery vehicles with PDA has the potential to improve their antimicrobial properties. This work describes the preparation of PDA-coated Zn-MOFs for improving curcumin's antibacterial properties against S. aureus and E. coli. Powder X-ray diffraction (P-XRD), FT-IR, scanning electron microscopy (SEM), and DLS were utilized to characterize PDA-coated Zn-MOFs. The curcumin loading and in vitro release of the prepared MOFs were also examined. Finally, the MOFs were tested for bactericidal ability against E. coli and S. aureus using an anti-bacterial assay and surface morphological analysis. Smaller size MOFs were capable of loading and releasing curcumin. The findings showed that as curcumin was encapsulated into PDA-coated MOFs, its bactericidal potential was significantly enhanced, and the findings were further supported by SEM which indicated the complete morphological distortion of the bacteria after treatment with PDA-Cur-Zn-MOFs. These studies clearly indicate that the PDA-Cur-Zn-MOFs developed in this study are extremely promising for long-term release of drugs to treat a wide range of microbial infections.

Investigation of wound healing potential of photo-active curcumin-ZnO-nanoconjugates in excisional wound model.

Wound healing, being a dynamic process consisting of hemostasis, inflammation, proliferation, and remodeling, involves the complicated interplay of various growth mediators and the cells associated repair system. Current wound healing therapies usually fail to completely regain skin integrity and functionality. Traditionally, curcumin is considered a potent natural wound healing agent as it possesses antibacterial, antioxidant, and anti-inflammatory properties. It is also known that zinc oxide (ZnO) nanoparticles (NPs) have photocatalytic properties, including the generation of reactive oxygen species. ZnO nanoaprticles are also Food and Drug Administration (FDA) approved as safe substances. While ZnO oxide requires illumination with ultraviolet light to become photocatalytically active, dye-sensitized ZnO can be activated by illumination with visible light. In the present study, we explored the wound healing potential of ZnO nanoparticles sensitized with curcumin (Cu+ZnO Nps) and illuminated with visible (blue) light generated by an array of high power LEDs. We studied the antibacterial effect of our conjugates by percentage reduction in bacterial growth and biofilm formation. The wound healing potential was analyzed by percentage wound contraction, biochemical parameters, and histopathological analysis of the wounded site. Additionally, angiogenesis and wound associated cytokines was evaluated by immunohistochemistry of CD31 and gene expression analysis of IL-1ß, TNF-α, and MMP-9 after 16 days of post-wound treatment, respectively. Our study suggests that the therapeutic effect of Cu+ZnO NPs with LED illumination increases its wound healing potential by producing an antibacterial and anti-inflammatory effect. Moreover, the treatment strategy of using a nano formulation in combination with LED illumination further increases its efficacy. It was concluded that the anti-inflammatory and bactericidal effects of the LED illuminated Cu+ZnO Np showed accelerated wound healing with increased wound contraction, collagen deposition, angiogenesis, and re-epithelialization.

Synthesis of Ribose-Coated Copper-Based Metal-Organic Framework for Enhanced Antibacterial Potential of Chloramphenicol against Multi-Drug Resistant Bacteria.

The rise in bacterial resistance to currently used antibiotics is the main focus of medical researchers. Bacterial multidrug resistance (MDR) is a major threat to humans, as it is linked to greater rates of chronic disease and mortality. Hence, there is an urgent need for developing effective strategies to overcome the bacterial MDR. Metal-organic frameworks (MOFs) are a new class of porous crystalline materials made up of metal ions and organic ligands that can vary their pore size and structure to better encapsulate drug candidates. This study reports the synthesis of ribose-coated Cu-MOFs for enhanced bactericidal activity of chloramphenicol (CHL) against Escherichia coli (resistant and sensitive) and MDR Pseudomonas aeruginosa. The synthesized Cu-MOFs were characterized with DLS, FT-IR, powder X-ray diffraction, scanning electron microscope, and atomic force microscope. They were further investigated for their efficacy against selected bacterial strains. The synthesized ribose-coated Cu-MOFs were observed as spherical shape structure with the particle size of 562.84 ± 13.42 nm. CHL caused the increased inhibition of E. coli and MDR P. aeruginosa with significantly reduced MIC and MBIC values after being encapsulated in ribose-coated Cu-MOFs. The morphological analysis of the bacterial strains treated with ribose-coated CHL-Cu-MOFs showed the complete morphological distortion of both E. coli and MDR P. aeruginosa. Based on the results of the study, it can be suggested that ribose-coated Cu-MOFs may be an effective alternate candidate to overcome the MDR and provide new perspective for the treatment of MDR bacterial infections.

Enhanced Antibacterial Potential of Amoxicillin against Helicobacter pylori Mediated by Lactobionic Acid Coated Zn-MOFs.

H. pylori (Helicobacter pylori) causes a common chronic infectious disease and infects around 4.4 billion people worldwide. H. pylori was classified as a member of the primary class of stomach cancer (stomach adenocarcinoma). Hence, this study was conducted to design a novel lactobionic acid (LBA)-coated Zn-MOFs to enhance bactericidal activity of Amoxicillin (AMX) against H. pylori. The synthesized Zn-MOFs were characterized by various techniques which included Dynamic Light Scattering (DLS), Fourier Transform Infrared (FT-IR) Spectroscopy, Powder X-ray diffraction, scanning electron microscope, and atomic force microscope. They were capable of encapsulating an increased amount of AMX and investigated for their efficacy to enhance the antibacterial potential of their loaded drug candidate. Interestingly, it was found that LBA-coated Zn-MOFs significantly reduced the IC50, MIC, and MBIC values of AMX against H. pylori. Morphological investigation of treated bacterial cells further authenticated the above results as LBA-coated Zn-MOFs-treated cells underwent complete distortion compared with non-coated AMX loaded Zn-MOFs. Based on the results of the study, it can be suggested that LBA-coated Zn-MOFs may be an effective alternate candidate to provide new perspective for the treatment of H. pylori infections.

Design and development of lipid modified chitosan containing muco-adhesive self-emulsifying drug delivery systems for cefixime oral delivery.

Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 µg/mL) and CFX-SNEDDs (9 ± 2 µg/mL) in comparison with control CFX (4 ± 1 µg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.

Synthesis of lactobionic acid based bola-amphiphiles and its application as nano-carrier for curcumin delivery to cancer cell cultures in-vitro.

Curcumin is highly effective against various types of cancers; however, its low aqueous solubility, high metabolism and non-specificity hinder its efficacy. This study reports the synthesis of three lactobionic acid containing bola-amphiphiles and their investigation for curcumin nano-vesicular delivery into cancer cells. Synthesized bola-amphiphiles were capable of forming nano-vesicles and curcumin loading in a lipophilicity dependent manner. Bola-amphiphile with higher lipophilicity (C12) caused 89.55 ± 5.52% drug encapsulation in its spherical shape nano-vesicles (195.90 ± 0.83 nm). Bola-amphiphile resulting increased curcumin encapsulation with minimum vesicles size was further investigated for cellular uptake and in-vitro anticancer activity. Anticancer activity of curcumin significantly increased against the tested cancer cells upon loading in bola-amphiphile nano-vesicles. Furthermore, nano-vesicular drug delivery of curcumin enhanced its cellular uptake even at the lowest concentration of 1.25 µg/mL.It is concluded that the synthesized bola-amphiphile based nano-vesicles can efficiently deliver curcumin to the tested cancer cells and needs to be tested for established anticancer drugs against different cancer cell lines for effective treatment of cancer.

Synthesis of biocompatible triazole based non-ionic surfactant and its vesicular drug delivery investigation.

Numerous nanotechnological approaches have been widely practiced to improve the bioavailability of less aqueous soluble drugs; phospholipid based vesicles (liposomes) being the most widely applied drug delivery system. However; due to stability issues, large scale production limitations, sterilization and long term storage problems; non-ionic surfactant based vesicles (niosomes) are considered their excellent counterparts. Niosomes are vesicles of non-ionic surfactants having the ability to carrying both hydrophilic and hydrophobic drugs in their inner aqueous or lipid bilayer compartments. In this research work, triazole based non-ionic surfactant (TBNIS) was synthesized and characterized by different spectroscopic techniques and then screened for biocompatibility using NIH 3T3 cell line, blood hemolysis assay and acute toxicity in mice. The synthesized surfactant was then checked for niosomes' formation, Amphotericin B loading and entrapment efficiency, drug release, stability and bioavailability of the drug was assessed and compared with free drug solution. The synthesized surfactant was found biocompatible and caused less blood hemolysis, greater cell vial ability and negligible toxicity in animals. The size of drug loaded niosomal vesicles of TBNIS based surfactant was 179.9 ± 3.23 nm with smaller size distribution i.e. 0.29 ± 0.02. The triazole based surfactant vesicles showed 88.76 ± 3.45 % drug entrapment efficiency, sustained drug release profile and stability. The drug in TBNIS based vesicles has greater oral bioavailability 0.099 ± 0.03 as compared to plan drug solution 0.012 ± 0.023 µg/mL. Results of this study suggests that the newly synthesized triazole based surfactant can be used in drug delivery for improving bioavailability of less water soluble drugs like Amphotericin B.

Synthesis of chitosan coated metal organic frameworks (MOFs) for increasing vancomycin bactericidal potentials against resistant S. aureus strain.

Multiple drug resistant (MDR) has become a major issue in developing countries. MDR bacterial infections lead to significant increase in morbidity, mortality and cost of prolonged treatments. Therefore, designing of strategies for improving the antimicrobial potential of the therapeutic agents are highly required. Metal organic frameworks (MOFs) are highly tunable hybrid material, consist of metal ions linked together by organic bridging ligands have been used as an efficient drug delivery carrier because of their biodegradability, low toxicity and structure integrity upon loading and functionalizing process. Current study was based on the synthesis of chitosan coated MOFs with enhanced contact with S. aureus cell surface. Chitosan is deacetylated derivative of chitin and capable for non-bonding interaction with negatively charged bacterial cell leading to enhanced contact of MOFs with S. aureus. Chitosan coated MOFs were characterized with various techniques such as atomic force microscopy, scanning electron microscopy, DLS, FT-IR, TGA, DSC and Powder X-ray diffraction. They were also studied for their efficacy on resistant S. aureus, results revealed that Vancomycin bactericidal activity significantly increased upon loading in chitosan coated MOFs and caused increased inhibition of resistant S. aureus. AFM analysis of S. aureus strains clearly revealed complete distortion of morphology by treating with chitosan modified drug loaded MOFs. Findings of the current study suggest the potential of chitosan coated MOFs for reversing bacterial resistance against Vancomycin and provide new perspectives for improved antibiotic therapy of infections associated with MDR.