Enzyme-responsive biomimetic solid lipid nanoparticles for antibiotic delivery against hyaluronidase-secreting bacteria.

In this work, a potent hyaluronidase inhibitor (ascorbyl stearate (AS)) was successfully employed to design vancomycin-loaded solid lipid nanoparticles (VCM-AS-SLNs) with biomimetic and enzyme-responsive features, to enhance the antibacterial efficacy of vancomycin against bacterial-induced sepsis. The VCM-AS-SLNs prepared were biocompatible and had appropriate physicochemical parameters. The VCM-AS-SLNs showed an excellent binding affinity to the bacterial lipase.

Synthesis of pH-responsive dimethylglycine surface-modified branched lipids for targeted delivery of antibiotics.

The rampant antimicrobial resistance crisis calls for efficient and targeted drug delivery of antibiotics at the infectious site. Hence, this study aimed to synthesize a pH-responsive dimethylglycine surface-modified branched lipid (DMGSAD-lipid). The structure of the synthesized lipid was fully confirmed.

Dual acting acid-cleavable self-assembling prodrug from hyaluronic acid and ciprofloxacin: A potential system for simultaneously targeting bacterial infections and cancer.

The incidence and of bacterial infections, and resulting mortality, among cancer patients is growing dramatically, worldwide. Several therapeutics have been reported to have dual anticancer and antibacterial activity. However, there is still an urgent need to develop new drug delivery strategies to improve their clinical efficacy.

A study of structure-activity relationship and anion-controlled quinolinyl Ag(I) complexes as antimicrobial and antioxidant agents as well as their interaction with macromolecules.

In this communication, we feature the synthesis and in-depth characterization of a series of silver(I) complexes obtained from the complexation of quinolin-4-yl Schiff base ligands ((E)-2-((quinolin-4-ylmethylene)amino)phenol L, 2-(quinolin-4-yl)benzo[d]thiazole L, (E)-N-(2-fluorophenyl)-1-(quinolin-4-yl)methanimine L, (E)-N-(4-chlorophenyl)-1-(quinolin-4-yl)methanimine L, (E)-1-(quinolin-4-yl)-N-(p-tolyl)methanimine L, (E)-1-(quinolin-4-yl)-N-(thiophen-2-ylmethyl)methanimine L) and three different silver(I) anions (nitrate, perchlorate and triflate). Structurally, the complexes adopted different coordination geometries, which included distorted linear or distorted tetrahedral geometry. The complexes were evaluated in vitro for their potential antibacterial and antioxidant activities.

A hyaluronic acid-based nanogel for the co-delivery of nitric oxide (NO) and a novel antimicrobial peptide (AMP) against bacterial biofilms.

Biofilms are a global health concern because they are associated with chronic and recurrent infections as well as resistance to conventional antibiotics. The aim of this study was to prepare a nanogel for the co-delivery of NO and AMPs against bacteria and biofilms. The NO-releasing nanogel was prepared by crosslinking HA solution with divinyl sulfone and extensively characterized.

Prevalence of plasmid-mediated AmpC beta-lactamases in Enterobacteria isolated from urban and rural folks in Uganda.

: AmpC beta-lactamase-producing bacteria are associated with increased resistance to third-generation cephalosporins. Here, we describe plasmid-mediated AmpC beta-lactamase-producing enterobacteria isolated from urban and rural dwellers in Uganda. : Stool and urine from 1,448 individuals attending outpatient clinics in Kampala and two rural districts in central Uganda were processed for isolation of and Klebsiella.

Copper(II)-N-hydroxy-N,N'-diarylformamidine complexes: Synthesis, crystal structures, antibacterial and molecular docking studies.

A series of Cu(II) complexes were synthesized by using N-hydroxy-N,N'-diarylformamidine ligands: N-hydroxy-N,N'-(phenyl)formamidine (L1), N-hydroxy-N'-(4-methylphenyl)formamidine (L2), N-hydroxy-N,N'-(2,6-dimethylphenyl)formamidine (L3), N-hydroxy-N,N'-(2,6-diisopropylphenyl)formamidine (L4). Reaction of ligands L1-L4 with hydrated copper acetate furnished mononuclear Cu(II) complexes 1-4 with general formula [Cu-(L)]. The molecular structures of complexes 3 and 4, as determined by single crystal X-ray diffraction, showed both to have square planar geometry with a near C symmetry.

Chitosan-Based Hydrogel for the Dual Delivery of Antimicrobial Agents Against Bacterial Methicillin-Resistant Biofilm-Infected Wounds.

Chronic wound infections caused by antibiotic-resistant bacteria have become a global health concern. This is attributed to the biofilm-forming ability of bacteria on wound surfaces, thus enabling their persistent growth. In most cases, it leads to morbidity and in severe cases mortality.

Formulation of pH responsive multilamellar vesicles for targeted delivery of hydrophilic antibiotics.

Fight against antimicrobial resistance calls for innovative strategies that can target infection sites and enhance activity of antibiotics. Herein is a pH responsive multilamellar vesicles (MLVs) for targeting bacterial infection sites. The vancomycin (VCM) loaded MLVs had 62.

A transferosome-loaded bigel for enhanced transdermal delivery and antibacterial activity of vancomycin hydrochloride.

Transdermal drug delivery is an attractive route of administration relative to other routes as it offers enhanced therapeutic efficacy. However, due to poor skin permeability of certain drugs, their application in transdermal delivery is limited. The ultra-deformable nature of transferosomes makes them suitable vehicles for transdermal delivery of drugs that have high molecular weights and hydrophilicity.

Biomimetic pH/lipase dual responsive vitamin-based solid lipid nanoparticles for on-demand delivery of vancomycin.

In this study, ascorbyl tocopherol succinate (ATS) was designed, synthesized and characterized via FT-IR, HR-MS, H NMR and C NMR, to simultaneously confer biomimetic and dual responsive properties of an antibiotic nanosystem to enhance their antibacterial efficacy and reduce antimicrobial resistance. Therefore, an in silico-aided design (to mimic the natural substrate of bacterial lipase) was employed to demonstrate the binding potential of ATS to lipase (-32.93 kcal/mol binding free energy (ΔG) and bacterial efflux pumps blocking potential (NorA ΔG: -37.

Cytotoxicity and Antibacterial Evaluation of O-Alkylated/Acylated Quinazolin-4-one Schiff Bases.

A series of quinazolin-4-one Schiff bases were synthesized and tested in vitro for their cytotoxicity against two cancerous cell lines (MCF-7, Caco-2) and a human embryonic cell line (HEK-293) including their antibacterial evaluation against two Gram-positive and four Gram-negative bacterial strains. Most of the quinazoline-Schiff bases exhibited potent cytotoxicity against Caco-2. 3-[(Z)-({4-[(But-2-yn-1-yl)oxy]phenyl}methylidene)amino]-2-methylquinazolin-4(3H)-one (6f) with the O-butyne functional group displayed three-fold higher cytotoxic activity (IC =376.

Quinoline Functionalized Schiff Base Silver (I) Complexes: Interactions with Biomolecules and In Vitro Cytotoxicity, Antioxidant and Antimicrobial Activities.

A series of fifteen silver (I) quinoline complexes - have been synthesized and studied for their biological activities. - were synthesized from the reactions of quinolinyl Schiff base derivatives - (obtained by condensing 2-quinolinecarboxaldehyde with various aniline derivatives) with AgNO, AgClO and AgCFSO. - were characterized by various spectroscopic techniques and the structures of [Ag()]NO, [Ag()]ClO, [Ag()]ClO, [Ag()]CFSO and [Ag()]CFSO were unequivocally determined by single crystal X-ray diffraction analysis.

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant .

Globally, human beings continue to be at high risk of infectious diseases caused by methicillin-resistant (MRSA); and current treatments are being depleted due to antimicrobial resistance. Therefore, the synthesis and formulation of novel materials is essential for combating antimicrobial resistance. The study aimed to synthesize a quaternary bicephalic surfactant (StBAclm) and thereof to formulate pH-responsive vancomycin (VCM)-loaded quatsomes to enhance the activity of the antibiotic against MRSA.

Novel formulation of antimicrobial peptides enhances antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA).

Antimicrobial peptides (AMPs) have the ability to penetrate as well as transport cargo across bacterial cell membranes, and they have been labeled as exceptional candidates to function in drug delivery. The aim of this study was to investigate the effectiveness of novel formulation of AMPs for enhanced MRSA activity. The strategy was carried out through the formulation of liposomes by thin-layer film hydration methodology, containing phosphatidylcholine, cholesterol, oleic acid, the novel AMP, as well as vancomycin (VCM).

A self-assembled polymer therapeutic for simultaneously enhancing solubility and antimicrobial activity and lowering serum albumin binding of fusidic acid.

The global antimicrobial resistance crisis has prompted worldwide efforts to develop new and more efficient antimicrobial compounds, as well as to develop new drug delivery strategies and targeting mechanisms. This study aimed to synthesize a novel polyethylene glycol-fusidic acid (PEG-FA) conjugate for self-assembly into nano-sized structures and explore its potential for simultaneously enhancing aqueous solubility and antibacterial activity of FA. In addition, the ability of PEG-FA to bind to HSA with lower affinity than FA is also investigated.

Supramolecular self-assembled drug delivery system (SADDs) of vancomycin and tocopherol succinate as an antibacterial agent: , and evaluations.

In this study self-assembled drug delivery system (SADDs) composed of a hydrophobic d-α-tocopherol succinate (TS) and a hydrophilic vancomycin (VCM) were formulated, and its potential for enhancing the antibacterial activity of VCM against (SA) and Methicillin-resistant (MRSA) were explored. The SADDs were synthesized via supramolecular complexation, then characterized for in silico, in vitro and in vivo studies. In silico studies confirmed the self-assembly of VCM/TS into NPs.

pH-Responsive Micelles From an Oleic Acid Tail and Propionic Acid Heads Dendritic Amphiphile for the Delivery of Antibiotics.

The aim of this study was to synthesize a novel biocompatible pH-responsive oleic acid-based dendritic lipid amphiphile (OLA-SPDA) which self-assembled into stable micelles (OLA-SPDA -micelles) with a relatively low critical micelle concentration (CMC) of 5.6 × 10 M. The formulated micelles had particle size, polydispersity index (PDI) and zeta potential (ZP) of 84.

Novel chitosan-based pH-responsive lipid-polymer hybrid nanovesicles (OLA-LPHVs) for delivery of vancomycin against methicillin-resistant Staphylococcus aureus infections.

The development of novel materials is necessary for adequate delivery of drugs to combat the Methicillin-resistant Staphylococcus aureus (MRSA) burden due to the limitations of conventional methods and challenges associated with antimicrobial resistance. Hence, this study aimed to synthesise a novel oleylamine based zwitterionic lipid (OLA) and explore its potential to formulate chitosan-based pH-responsive lipid-polymer hybrid nanovesicles (VM-OLA-LPHVs1) to deliver VM against MRSA. The OLA was synthesised, and the structure characterised by H NMR, C NMR, FT-IR and HR-MS.

AB2-type amphiphilic block copolymer containing a pH-cleavable hydrazone linkage for targeted antibiotic delivery.

A novel AB2-type amphiphilic block copolymer [OA-CN-NH-(PEG)] with hydrazone linkage was synthesized and explored for pH-triggered antibiotic delivery. Vancomycin (VCM) loaded micelles of the polymer [OA-CN-NH-(PEG)-VCM] were spherical in shape with size, polydispersity index, zeta potential and entrapment efficiency of 130.33 ± 7.

Supramolecular amphiphiles of Beta-cyclodextrin and Oleylamine for enhancement of vancomycin delivery.

The global threat of antimicrobial resistant strains calls for innovative strategies to utilize nano drug delivery systems to enhance the delivery of antibiotics, thus reducing the development of resistance. Supramolecular amphiphiles that can self-assemble into nanostructures are one such nano delivery system, that are showing potential for effective drug delivery. The aim of this study was to synthesize and formulate a novel sugar-based cationic amphiphile (BCD-OLA) derivative from a Beta-cyclodextrin (BCD) head and long C18 carbon chain with a terminal amine; oleylamine (OLA), using inclusion complexation for application in antibiotic delivery.

Liposomes with pH responsive 'on and off' switches for targeted and intracellular delivery of antibiotics.

pH responsive drug delivery systems are one of the new strategies to address the spread of bacterial resistance to currently used antibiotics. The aim of this study was to formulate liposomes with 'On' and 'Off'' pH responsive switches for infection site targeting. The vancomycin (VCM) loaded liposomes had sizes below 100 nm, at pH 7.

Self-assembled oleylamine grafted hyaluronic acid polymersomes for delivery of vancomycin against methicillin resistant Staphylococcus aureus (MRSA).

MRSA infections are a major global healthcare problem associated with high morbidity and mortality. The application of novel materials in antibiotic delivery has efficiently contributed to the treatment of MRSA infections. The aim of the study was to develop novel hyaluronic acid-oleylamine (HA-OLA) conjugates with 25-50% degrees of conjugation, for application as a nano-drug carrier with inherent antibacterial activity.

Novel two-chain fatty acid-based lipids for development of vancomycin pH-responsive liposomes against and methicillin-resistant (MRSA).

The development of bacterial resistance against antibiotics is attributed to poor localisation of lethal antibiotic dose at the infection site. This study reports on the synthesis and use of novel two-chain fatty acid-based lipids (FAL) containing amino acid head groups in the formulation of pH-responsive liposomes for the targeted delivery of vancomycin (VAN). The formulated liposomes were characterised for their size, polydispersity index (PDI), surface charge and morphology.