Disease-Inspired Design of Biomimetic Tannic Acid-Based Hybrid Nanocarriers for Enhancing the Treatment of Bacterial-Induced Sepsis.

This study explored the development of novel biomimetic tannic acid-based hybrid nanocarriers (HNs) for targeted delivery of ciprofloxacin (CIP-loaded TAH-NPs) against bacterial-induced sepsis. The prepared CIP-loaded TAH-NPs exhibited appropriate physicochemical characteristics and demonstrated biocompatibility and nonhemolytic properties. Computational simulations and microscale thermophoresis studies validated the strong binding affinity of tannic acid (TA) and its nanoformulation to human Toll-like receptor 4, surpassing that of the natural substrate lipopolysaccharide (LPS), suggesting a potential competitive inhibition against LPS-induced inflammatory responses. CIP released from TAH-NPs displayed a sustained release profile over 72 h. The in vitro antibacterial activity studies revealed that CIP-loaded TAH-NPs exhibited enhanced antibacterial efficacy and efflux pump inhibitory activity. Specifically, they showed a 3-fold increase in biofilm eradication activity against MRSA and a 2-fold increase against P. aeruginosa compared to bare CIP. Time-killing assays demonstrated complete bacterial clearance within 8 h of treatment with CIP-loaded TAH-NPs. In vitro DPPH scavenging and anti-inflammatory investigations confirmed the ability of the prepared hybrid nanosystem to neutralize reactive oxygen species (ROS) and modulate LPS-induced inflammatory responses. Collectively, these results suggest that CIP-loaded TAH-NPs may serve as an innovative nanocarrier for the effective and targeted delivery of antibiotics against bacterial-induced sepsis.

Supramolecular self-assembled drug delivery system (SADDs) of vancomycin and tocopherol succinate as an antibacterial agent: in vitro, in silico and in vivo 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 Staphylococcus aureus (SA) and Methicillin-resistant Staphylococcus aureus (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. The size, surface charge and drug loading of the SADDs was ˂100 nm, -27 mV and 68%, respectively. The SADDs were non-hemolytic and biosafe. A sustained release of VCM from SADDs was noted, with 52.2% release after 48 hr. The in vitro antibacterial test showed a twofold decrease in Minimum inhibitory concentration (MIC) against SA and MRSA, and a significantly higher reduction in MRSA biofilms compared to bare VCM. Further, in silico studies confirmed strong and stable binding of TS to MRSA efflux pumps. The in vivo study using mice skin infection models showed a 9.5-fold reduction in bacterial load after treatment with SADDs, in comparison with bare VCM. These findings affirmed that VCM/TS NPs as a promising novel nano-delivery for treating bacterial infections.

The Performance of Diagnostic Tests for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the South African Population: A Scoping Review.

To determine the performance and reliability of diagnostic tests for the identification of SARS-CoV-2 infection in South Africa, we conducted a scoping review to identify published studies undertaken in the English language from March 2020 to August 2022 that evaluated the performance of antigen- and antibody-based diagnostic tests for SARS-CoV-2 in South Africa. We identified 17 relevant peer-reviewed articles; six reported on SARS-CoV-2 gene and/or antigen detection whilst 11 reported on antibody detection. Of the SARS-CoV-2 gene and/or antigen-based tests, sensitivity ranged from 40% to 100%, whilst for the antibody-based tests, sensitivity ranged from 13% to 100%. All tests evaluated were highly dependent on the stage of infection and the timing of sample collection. This scoping review demonstrated that no single SARS-CoV-2 gene and/or antigen- or antibody-based assay was sufficiently sensitive and specific simultaneously. The sensitivity of the tests was highly dependent on the timing of sample collection with respect to SARS-CoV-2 infection. In the case of SARS-CoV-2 gene and/or antigen detection, the earlier the collection of samples, the greater the sensitivity, while antibody detection tests showed better sensitivity using samples from later stages of infection.

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. The in vitro drug release study showed that the release of the loaded vancomycin was significantly accelerated by the bacterial lipase. The in silico simulations and MST studies confirmed the strong binding affinity of AS and VCM-AS-SLNs to bacterial hyaluronidase compared to its natural substrate. This binding superiority indicates that AS and VCM-AS-SLNs could competitively inhibit the effect of hyaluronidase enzyme, and thus block its virulence action. This hypothesis was further confirmed using the hyaluronidase inhibition assay. The in vitro antibacterial studies against sensitive and resistant Staphylococcus aureus revealed that the VCM-AS-SLNs had a 2-fold lower minimum inhibitory concentration, and a 5-fold MRSA biofilm elimination compared to the free vancomycin. Furthermore, the bactericidal-kinetic showed a 100% bacterial clearance rate within 12 h of treatment with VCM-AS-SLNs, and <50 % eradication after 24 h for the bare VCM. Therefore, the VCM-AS-SLN shows potential as an innovative multi-functional nanosystem for effective and targeted delivery of antibiotics.

The link between relative stability constant of DNA- and BSA-chromenopyrimidine complexes and cytotoxicity towards human breast cancer cells (MCF-7).

In this study, we synthesized and characterized ten chromenopyrimidine derivatives using analytical and spectroscopic methods. Studies on DNA and albumin binding affinity, as well as cytotoxicity tests on human breast cancer (MCF-7) cells, of the chromenopyrimidines, were conducted. The natural logarithm of the relative stability constant of DNA- and BSA-chromenopyrimidine complexes [ln(KDNA/KBSA)] was used as a criterion for selecting compounds for cytotoxicity studies. We found that ln(KDNA/KBSA) was inversely related to IC50 values of the compounds in MCF-7 cells. The antiproliferative effects of the compounds were found to induce apoptosis in MCF-7 cells, which is a desired mechanism of cell death. Correlations between the DNA and albumin binding affinities of chromenopyrimidines were established. We propose that this relationship approach can, for a given set of compounds, assist in predicting the cytotoxicity of potential drug candidates towards MCF-7 cells based on their experimentally determined CT-DNA and BSA binding affinities.

Exploring the applications of hyaluronic acid-based nanoparticles for diagnosis and treatment of bacterial infections.

Hyaluronic acid (HA) has become a topic of significant interest in drug delivery research due to its excellent properties, including biosafety, biodegradability, and nonimmunogenicity. Moreover, due to its ease of modification, HA can be used to prepare several HA-based nanosystems using various approaches. These approaches involve conjugating/grafting of hydrophobic moieties, polyelectrolytes complexation with cationic polymers, or surface modification of various nanoparticles using HA. These nanoparticles are able to selectively deliver antibacterial drugs or diagnostic molecules into the site of infections. In addition, HA can bind with overexpressed cluster of differentiation 44 (CD44) receptors in macrophages and also can be degraded by a family of enzymes called hyaluronidase (HAase) to release drugs or molecules. By binding with these receptors or being degraded at the infection site by HAase, HA-based nanoparticles allow enhanced and targeted antibacterial delivery. Herein, we present a comprehensive and up-to-date review that highlights various techniques of preparation of HA-based nanoparticles that have been reported in the literature. Furthermore, we also discuss and critically analyze numerous types of HA-based nanoparticles that have been employed in antibacterial delivery to date. This article offers a critical overview of the potential of HA-based nanoparticles to overcome the challenges of conventional antibiotics in the treatment of bacterial infections. Moreover, this review identifies further avenues of research for developing multifunctional and biomimetic HA-based nanoparticles for the treatment, prevention, and/or detection of pathogenic bacteria. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection.

Cellular senescence, a hallmark of ageing, contributes to tissue or organ dysfunction and the pathophysiology of diverse age-related diseases (ARD) by various mechanisms. Targeting it by selective elimination of senescent cells (SCs) or blocking senescence-associated secretory phenotypes (SASP) with natural or synthetic compounds has been suggested to improve lifespan. Dietary phytochemicals possess a broad spectrum of biochemical and pharmacological effects that are beneficial to human health. Flavonoids, which are widely consumed in fruits and vegetables worldwide, are emerging as potential therapeutic agents to mitigate senescence. Naringenin, hesperetin, hesperidin, quercetin, fisetin, kaempferol, rutin, apigenin, luteolin, nobiletin, tangeretin, genistein, wogonin, epigallocatechin gallate (EGCG), theaflavin-3-gallate (TF2A), and procyanidin C1 possess potent antisenescence effects. A single biochemical process may not explain their pleiotropic pharmacological impact. Flavonoids directly modulate underlying cellular senescence processes or interact with molecular targets that regulate ageing-related pathways. This review discusses the potential use of flavonoids to mitigate senescence and consequently delay the onset of ageing-related diseases. We also highlight the underlying mechanisms of action of flavonoids as potential senotherapeutics and reflect on future perspectives and possible strategies to optimize and increase the translatability from bench to bedside in senotherapy.

Synergism Potentiates Oxidative Antiproliferative Effects of Naringenin and Quercetin in MCF-7 Breast Cancer Cells.

Breast cancer (BC) is the most frequently diagnosed type of cancer as of 2020. Quercetin (Que) and Naringenin (Nar) are predominantly found in citrus fruits and vegetables and have shown promising antiproliferative effects in multiple studies. It is also known that the bioactive effects of these flavonoids are more pronounced in whole fruit than in isolation. This study investigates the potential synergistic effects of Que and Nar (CoQN) in MCF-7 BC cells. MCF-7 cells were treated with a range of concentrations of Que, Nar or CoQN to determine cell viability. The IC50 of CoQN was then used to investigate caspase 3/7 activity, Bcl-2 gene expression, lipid peroxidation and mitochondrial membrane potential to evaluate oxidative stress and apoptosis. CoQN treatment produced significant cytotoxicity, reduced Bcl-2 gene expression and increased caspase 3/7 activity compared to either Nar or Que. Furthermore, CoQN significantly increased lipid peroxidation and reduced mitochondrial membrane potential (MMP) compared to either Nar or Que. Therefore, CoQN treatment has potential pharmacological application in BC chemotherapy by inducing oxidative stress and apoptosis in MCF-7 BC cells. The results of this study support the increased consumption of whole fruits and vegetables to reduce cell proliferation in cancer.

Engineering hybrid nanosystems for efficient and targeted delivery against bacterial infections.

Hybrid nanoparticles (NPs) are emerging as superior alternatives to conventional nanocarriers for enhancing the delivery of antibiotics and improving their targeting at the infection site, resulting in the eradication of bacterial infections and overcoming antimicrobial resistance. They can specifically control the release of antibiotics when reaching the targeted site of infection, thus enhancing and prolonging their antimicrobial efficacy. In this review, we provide a comprehensive and an up-to-date overview of the recent advances and contributions of lipid-polymer hybrid NPs; organic-inorganic hybrid NPs; metal-organic frameworks; cell membrane-coated hybrid NPs; hybrid NP-hydrogels; and various others, that have been reported in the literature for antibacterial delivery, with emphasis on their design approaches; the nanomaterials constructed; the mechanisms of drug release; and the enhanced antibacterial efficacy of the reported hybrid nanocarriers. This review also highlights future strategies that can be used to improve the potential of hybrid nanosystems to treat bacterial infections and overcome antibiotic resistance.

Stimuli-responsive and biomimetic delivery systems for sepsis and related complications.

Sepsis, a consequence of an imbalanced immune response to infection, is currently one of the leading causes of death globally. Despite advances in the discoveries of potential targets and nanotechnology, sepsis still lacks effective drug delivery systems for optimal treatment. Stimuli-responsive and biomimetic nano delivery systems, specifically, are emerging as advanced bio-inspired nanocarriers for enhancing the treatment of sepsis. Herein, we present a critical review of different stimuli-responsive systems, including pH-; enzyme-; ROS- and toxin-responsive nanocarriers, reported in the delivery of therapeutics for sepsis. Biomimetic nanocarriers, utilizing natural pathways in the inflammatory cascade to optimize sepsis therapy, are also reviewed, in addition to smart, multifunctional vehicles. The review highlights the nanomaterials designed for constructing these systems; their physicochemical properties; the mechanisms of drug release; and their potential for enhancing the therapeutic efficacy of their cargo. Current challenges are identified and future avenues for research into the optimization of bio-inspired nano delivery systems for sepsis are also proposed. This review confirms the potential of stimuli-responsive and biomimetic nanocarriers for enhanced therapy against sepsis and related complications.

Surface modification of nano-drug delivery systems for enhancing antibiotic delivery and activity.

Rampant antimicrobial resistance calls for innovative strategies to effectively control bacterial infections, enhance antibacterial efficacy, minimize side effects, and protect existing antibiotics in the market. Therefore, to enhance the delivery of antibiotics and increase their bioavailability and accumulation at the site of infection, the surfaces of nano-drug delivery systems have been diversely modified. This strategy applies various covalent and non-covalent techniques to introduce specific coating materials that have been found to be effective against various sensitive and resistant microorganisms. In this review, we discuss the techniques of surface modification of nanocarriers loaded with antibacterial agents. Furthermore, saccharides, polymers, peptides, antibiotics, enzymes and cell membranes coatings that have been used for surface functionalization of nano-drug delivery systems are described, emphasizing current approaches for enhancing delivery, bioavailability, and efficacy of surface-modified antibacterial nanocarriers at infection sites. This article offers a critical overview of the potential of surface-modified antibacterial nanocarriers to overcome the limitations of conventional antibiotics in the treatment of bacterial infections. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

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. The nanogel was found to be biocompatible, injectable and NO release from the gel was sustained over a period of 24 h. In vitro antibacterial studies showed that the NO-AMP-loaded nanogel exhibited a broad spectrum antibacterial/antibiofilm activity. The NO-releasing nanogel had a greater antibacterial effect when compared to NO alone with MIC values of 1.56, 0.78 and 0.39 µg/ml against Escherichia coli, Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa bacteria respectively. The antibiofilm results showed there was a 12.5 and 24-folds reduction in biofilms of MRSA, and P. aeruginosa respectively for catheters exposed to nanogel loaded with AMP/NO when compared to only NO, while a 7 and 9.4-folds reduction in biofilms of MRSA, and P. aeruginosa respectively was displayed by the nanogel loaded with only NO compared to only NO. The AMP/NO-releasing nanogel showed the potential to combat both biofilms and bacterial infections.

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. The lipid polymer hybrid nanoparticles (LPHNPs) were formulated using the solvent evaporation method and characterised. Two LPHNPs (VCM_HS15_LPHNPs and VCM_RH40_LPHNPs) were formulated and characterised for size, polydispersity index (PDI), and zeta potential (ZP). Atomistic molecular dynamics simulations revealed that both the systems self-assembled to form energetically stable aggregates. The ZP of RH40_VCM_LPHNPs changed from 0.55 ± 0.14-9.44 ± 0.33 Vm, whereas for SH15_VCM_LPHNPs, ZP changed from - 1.55 ± 0.184 Vm to 9.83 ± 0.52 Vm at pH 7.4 and 6.0, respectively. The encapsulation efficiencies of VCM were above 40% while the drug release was faster at acidic pH when compared to pH 7.4. The antibacterial activity of LPHNPs against MRSA was eight-fold better in MICs at pH 6.0, compared to 7.4, when compared to bare VCM-treated specimens. The study confirms that pH-responsive LPHNPs have the potential for enhancing the treatment of bacterial infections and other diseases characterised by acidic conditions at the target site.

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. Therefore, this study aimed to develop a novel acid cleavable prodrug (HA-Cip) from ciprofloxacin and hyaluronic acid to simultaneously enhance the anticancer and antibacterial properties of Cip as a superior drug delivery system. HA-Cip was synthesised and characterised (FT-IR, HR-MS, and H1 NMR). HA-Cip generated stable micelles with an average particle size, poly dispersion index (PDI) and zeta potential (ZP) of 237.89 ± 25.74 nm, 0.265 ± 0.013, and -17.82 ± 1.53 mV, respectively. HA-Cip showed ≥80 % cell viability against human embryonic kidney 293 cells (non-cancerous cells), ˂0.3 % haemolysis; and a faster pH-responsive ciprofloxacin release at pH 6.0. HA-Cip showed a 5.4-fold improvement in ciprofloxacin in vitro anticancer activity against hepatocellular cancer (HepG2) cells; and enhanced in vitro antibacterial activity against Escherichia coli and Klebsiella pneumoniae at pH 6.0. Our findings show HA-Cip as a promising prodrug for targeted delivery of ciprofloxacin to efficiently treat bacterial infections associated, and/or co-existing, with cancer.

Biomimetic strategies for enhancing synthesis and delivery of antibacterial nanosystems.

The identification of bacterial infections as a significant human-life threatening challenge is driving several research efforts toward generating new strategies to treat bacterial infections and associated resistance issues. Biomimicry is an emerging field demonstrating great potential for application in the war against bacterial infection and their associated diseases. Recently, nanotechnology combined with biomimetic concepts has been identified as an innovative strategy to combat bacterial infections. Herein, we present an up-to-date review of biomimetic antibacterial nanosystems, with a focus on the different biomimetic approaches involved in the synthesis and delivery of antibacterial nanosystems. Biomimetic synthesis and nanosystems involved in mimicking cellular structures, extracellular matrix structures and biological surfaces are critically reviewed. Their advantages achieved in biocompatibility, biodegradability, improvement of pharmacokinetics parameters and antibacterial efficiency are highlighted. Current challenges and recommendations for amplifying the potential of these systems are also identified. This review illustrates the significant impact and potential of biomimetic antibacterial nanosystems in the field of bacterial infection treatment.

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. However, their low viscosity, which leads to low contact time on the surface of the skin, has restricted their application in transdermal delivery. Therefore, this study aimed to deliver transferosomes loaded with a highly water-soluble and high molecular weight vancomycin hydrochloride (VCM-HCl) via a bigel for systemic delivery and treatment of microbial infections. VCM-HCl-loaded transferosomal formulations (TNFs) were prepared using a reverse-phase evaporation method and then loaded into a bigel. Both the TNFs and TNFs-loaded bigel (TNF-L-B) were characterized by a range of in vitro and ex vivo techniques. TNFs and TNF-L-B were tested for biosafety via the MTT assay and found to be biosafe. Prepared TNFs had sizes, zeta potential and entrapment efficiency of 63.02 ± 5.34 nm, -20.93 ± 6.13 mV and 84.48 ± 1.22% respectively. VCM-HCl release from TNF-L-B showed a prolonged release profile with 39.76 ± 1.6% after 24hrs when compared to bare VCM-HCl loaded in the bigel (74.81 ± 8.84%). Ex-vivo permeation of prepared TNF-L-B showed a higher permeation flux of 0.56 µg/cm2/h compared to the bare VCM-HCl-loaded bigel of 0.23 µg/cm2/h, indicating superior permeation and bioavailability of the drug. Additionally, the prepared TNF-L-B demonstrated improved antimicrobial activity. The TNF-L-B showed minimum inhibitory concentrations (MIC) of 0.97 µg/ml against Staphylococcus aureus (SA) and 1.95 µg/ml against methicillin-resistant SA (MRSA), which were 2-fold lower MIC values than the bare drug. The time-kill assay showed that both TNFs and TNF-L-B systems caused a 5.6-log reduction (100%) in MRSA compared to bare VCM-HCl after 24 hrs of incubation. Furthermore, as opposed to the bare VCM-HCl solution, the degree of biofilm reduction caused by TNFs (55.72%) and TNF-L-B (34.58%) suggests their dominance in eradicating MRSA biofilm. These findings indicate that TNF-L-B is a promising system for transdermal delivery of hydrophilic and high molecular weight drugs.

Novel Biomimetic Human TLR2-Derived Peptides for Potential Targeting of Lipoteichoic Acid: An In Silico Assessment.

Antimicrobial resistance is one of the most significant threats to health and economy around the globe and has been compounded by the emergence of COVID-19, raising important consequences for antimicrobial resistance development. Contrary to conventional targeting approaches, the use of biomimetic application via nanoparticles for enhanced cellular targeting, cell penetration and localized antibiotic delivery has been highlighted as a superior approach to identify novel targeting ligands for combatting antimicrobial resistance. Gram-positive bacterial cell walls contain lipoteichoic acid (LTA), which binds specifically to Toll-like receptor 2 (TLR2) on human macrophages. This phenomenon has the potential to be exploited for the design of biomimetic peptides for antibacterial application. In this study, we have derived peptides from sequences present in human TLR2 that bind to LTA with high affinity. In silico approaches including molecular modelling, molecular docking, molecular dynamics, and thermodynamics have enabled the identification of these crucial binding amino acids, the design of four novel biomimetic TLR2-derived peptides and their LTA binding potential. The outcomes of this study have revealed that one of these novel peptides binds to LTA more strongly and stably than the other three peptides and has the potential to enhance LTA targeting and bacterial cell penetration.

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, H1 NMR and C13 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 (ΔGbind) and bacterial efflux pumps blocking potential (NorA ΔGbind: -37.10 kcal/mol, NorB ΔGbind: -34.46 kcal/mol). ATS bound stronger to lipase than the natural substrate (35 times lower Kd value). The vancomycin loaded solid lipid nanoparticles (VM-ATS-SLN) had a hydrodynamic diameter, zeta potential, polydispersity index and entrapment efficiency of 106.9 ± 1.4 nm, -16.5 ± 0.93 mV, 0.11 ± 0.012 and 61.9 ± 1.31%, respectively. In vitro biocompatibility studies revealed VM-ATS-SLN biosafety and non-haemolytic activity. Significant enhancement in VM release was achieved in response to acidified pH and lipase enzyme, compared to controls. VM-ATS-SLN showed enhanced sustained in vitro antibacterial activity for 5 days, 2-fold greater MRSA biofilm growth inhibition and 3.44-fold reduction in bacterial burden in skin infected mice model compared to bare VM. Therefore, ATS shows potential as a novel multifunctional adjuvant for effective and targeted delivery of antibiotics.

Chitosan-Based Hydrogel for the Dual Delivery of Antimicrobial Agents Against Bacterial Methicillin-Resistant Staphylococcus aureus 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. Current conventional approaches used in the treatment of biofilm wounds are proving to be ineffective due to limitations such as the inability to penetrate the biofilm matrix; hence, biofilm-related wounds remain a challenge. Therefore, there is a need for more efficient alternate therapeutic interventions. Hydrogen peroxide (HP) is a known antibacterial/antibiofilm agent; however, prolonged delivery has been challenging due to its short half-life. In this study, we developed a hydrogel for the codelivery of HP and antimicrobial peptides (Ps) against bacteria, biofilms, and wound infection associated with biofilms. The hydrogel was prepared via the Michael addition technique, and the physiochemical properties were characterized. The safety, in vitro, and in vivo antibacterial/antibiofilm activity of the hydrogel was also investigated. Results showed that the hydrogel is biosafe. A greater antibacterial effect was observed with HP-loaded hydrogels (CS-HP; hydrogel loaded with HP and CS-HP-P; hydrogel loaded with HP and peptide) when compared to HP as seen in an approximately twofold and threefold decrease in minimum inhibitory concentration values against methicillin-resistant Staphylococcus aureus (MRSA) bacteria, respectively. Similarly, both the HP-releasing hydrogels showed enhanced antibiofilm activity in the in vivo study in mice models as seen in greater wound closure and enhanced wound healing in histomorphological analysis. Interestingly, the results revealed a synergistic antibacterial/antibiofilm effect between HP and P in both in vitro and in vivo studies. The successfully prepared HP-releasing hydrogels showed the potential to combat bacterial biofilm-related infections and enhance wound healing in mice models. These results suggest that the HP-releasing hydrogels may be a superior platform for eliminating bacterial biofilms without using antibiotics in the treatment of chronic MRSA wound infections, thus improving the quality of human health.