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Abstract Introduction The application of biomimetic and stimuli-responsive nanocarriers displays considerable promise in improving the management of bacterial sepsis and overcoming antimicrobial resistance. Therefore, the study aimed to synthesize a novel hyaluronic acid-lysine conjugate (HA-Lys) and to utilize the attributes of the synthesized HA-Lys with Tocopherol succinate (TS) and Oleylamine (OLA) in the formulation of multifunctional biomimetic pH-responsive HNLCs loaded with vancomycin (VCM-HNLCs), to combat bacterial sepsis. Methods A novel hyaluronic acid-lysine conjugate (HA-Lys) was synthesized and characterized using FTIR and 1H NMR spectroscopy. Vancomycin-loaded hybrid nanosystems (VCM-HNLCs) were prepared through hot homogenization ultrasonication and evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%). In vitro biocompatibility was assessed via MTT assay and red blood cell hemolysis test. The binding affinity to TLR2 and TLR4 was measured using microscale thermophoresis (MST). Drug release was evaluated using the dialysis bag method. Antimicrobial activity against MRSA and efflux pump inhibition were also determined. Efficacy was demonstrated in an MRSA-induced sepsis mice model. Results The VCM-HNLCs, produced via hot homogenization ultrasonication, exhibited particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%) of 110.77 ± 1.692 nm, 0.113 ± 0.022, − 2.92 ± 0.210 mV, and 76.27 ± 1.200%, respectively. In vitro, biocompatibility was proven by hemolysis and cytotoxicity studies. The VCM-HNLCs demonstrated targetability to human Toll-like receptors (TLR 2 and 4) as validated by microscale thermophoresis (MST). VCM-HNLCs showed a twofold reduction in MIC values at physiological pH compared to the bare VCM against S. aureus and MRSA for 48 h. While at pH 6.0, MIC values were reduced by fourfold in the first 24 h and by eightfold in the subsequent 48 and 72 h against tested strains. Furthermore, VCM-HNLCs showed inhibitory effects against MRSA efflux pumps, reactive oxygen species (ROS), and lipopolysaccharide (LPS)-induced hyperinflammation. In an MRSA-induced sepsis mice model, VCM-HNLCs demonstrated superior efficacy compared to free VCM, significantly eliminated bacteria and improved survival rates. Conclusions Overall, these results highlight the potential of VCM-HNLCs as novel multifunctional nanocarriers to combat antimicrobial resistance (AMR) and enhance sepsis outcomes. Graphical Abstract more...

Abstract Sepsis represents a critical medical condition stemming from an imbalanced host immune response to infections, which is linked to a significant burden of disease. Despite substantial efforts in laboratory and clinical research, sepsis remains a prominent contributor to mortality worldwide. Nanotechnology presents innovative opportunities for the advancement of sepsis diagnosis and treatment. Due to their unique properties, including diversity, ease of synthesis, biocompatibility, high specificity, and excellent pharmacological efficacy, peptides hold great potential as part of nanotechnology approaches against sepsis. Herein, we present a comprehensive and up-to-date review of the applications of peptides in nanosystems for combating sepsis, with the potential to expedite diagnosis and enhance management outcomes. Firstly, sepsis pathophysiology, antisepsis drug targets, current modalities in management and diagnosis with their limitations, and the potential of peptides to advance the diagnosis and management of sepsis have been adequately addressed. The applications have been organized into diagnostic or managing applications, with the last one being further sub-organized into nano-delivered bioactive peptides with antimicrobial or anti-inflammatory activity, peptides as targeting moieties on the surface of nanosystems against sepsis, and peptides as nanocarriers for antisepsis agents. The studies have been grouped thematically and discussed, emphasizing the constructed nanosystem, physicochemical properties, and peptide-imparted enhancement in diagnostic and therapeutic efficacy. The strengths, limitations, and research gaps in each section have been elaborated. Finally, current challenges and potential future paths to enhance the use of peptides in nanosystems for combating sepsis have been deliberately spotlighted. This review reaffirms peptides' potential as promising biomaterials within nanotechnology strategies aimed at improving sepsis diagnosis and management. Graphical Abstract more...

Abstract Alarming sepsis‐related mortality rates present significant challenges to healthcare services globally. Despite advances made in the field, there is still an urgent need to develop innovative approaches that could improve survival rates and reduce the overall cost of treatment for sepsis patients. Therefore, this study aimed to develop a novel multifunctional therapeutic agent for advanced control of bacterial sepsis. Extracellular vesicles (EVs) isolated from lipopolysaccharide (LPS) induced HepG2 (hepatocellular carcinoma cells) (iEV) displayed an average particle size of 171.63 ± 2.77 nm, a poly dispersion index (PDI) of 0.32 ± 0.0, and a zeta potential (ZP) of −11.87 ± 0.18 mV. Compared to HepG2 EV, LPS induction significantly increases the EV protein concentration, PDI and ZP, reduces the average size and promotes cell proliferation and cytoprotective effects of the isolated EVs (iEVs) against LPS‐induced cytotoxicity. Coating of iEV with a cationic antimicrobial peptide (AMP) to form PC‐iEV slightly changed their physical properties and shifted their surface charge toward neutral values. This modification improved the antibacterial activity (2‐fold lower minimum bactericidal concentration [MBC] values) and biocompatibility of the conjugated peptide while maintaining iEV cytoprotective and anti‐inflammatory activities. Our findings indicate the superior anti‐inflammatory and antibacterial dual activity of PC‐iEV against pathogens associated with sepsis. more...

The study examined the heavy metal concentrations in the tissues of Carica papaya (CP) tissues and soil in Eneka Dumpsite, Port Harcourt, Nigeria. A transect of 100 m x 300 m was laid from the center of the dumpsite. In the transect a 20 m x 20 m quadrat was established at 10 m, 20 m, 50 m, and 300 m (control) from the dumpsite whereby the soil samples and CP tissues (leaf, fruit and root) were collected. Standard laboratory techniques were used to determine the heavy metals in the soil samples and CP tissues. Results showed that heavy metals in CP and soil decreased with increasing distance from the dumpsite. Fe, Pb and Cu in CP tissues varied significantly with distance. In conclusion, there is accumulation of heavy metals in CP around dumpsite and human consumption of such CP should be reduced or totally avoided. more...

Background: South Africa has a high burden of tuberculosis (TB), with high human immunodeficiency virus (HIV)-TB co-infection rates and the emergence of multidrugresistant TB. Objectives: To describe treatment outcomes and factors influencing outcomes amongst pulmonary TB (PTB) patients in the Limpopo Province. Method: A retrospective review was conducted of data on the provincial electronic TB register (ETR.net) for the years 2006 to 2010 (inclusive), and a random sample of 1200 records was selected for further analysis. The Chi square test was used to examine the influence of age, gender, health facility level, diagnostic category and treatment regimen on treatment outcomes. Results: Overall 90 617 (54.6% male) PTB patients were registered between 2006 and 2010. Of the sampled 1200 TB cases, 72.6% were in persons aged 22 to 55 years and 86.2% were new cases. The TB mortality rate was 13.6% (much higher than the World Health Organization target of 3%), whilst the default rate was 9.8%. There was a strong association between age (P < 0.001), diagnostic category (P < 0.001), treatment regimen (P < 0.001), and health facility level (P < 0.001) and treatment outcome. Those aged 22–55, and 56–74 years were more likely to die (P < 0.05). Poor treatment outcomes were also associated with initial treatment failure, receiving treatment at hospital and treatment regimen II. Conclusion: The poor TB treatment outcomes in Limpopo, characterised by a high mortality and default rates, call for strengthening of the TB control programme, which should include integration of HIV and/or AIDS and TB services. more...

Surface functionalization of nanoparticles has shown potential in enhancing the efficacy of antibiotic-loaded nanosystems against drug-resistant bacteria. The objective of this study was to synthesize and characterize an acid-cleavable pH-responsive polymer from methoxy polyethylene glycol and oleylamine (mPEG-OA) to surface modify vancomycin (VCM)-loaded niosomes and to evaluate their antibacterial and anti-biofilm effectiveness against methicillin-resistant Staphylococcus aureus (MRSA). The novel mPEG-OA-coated niosomes were biocompatible, hemocompatible with size, polydispersity index, and zeta potential of 169.2 ± 1.6 nm, 0.21 ± 0.01 and −0.82 ± 0.22 mV, respectively. Under acidic conditions, mPEG-OA-coated niosomes exhibited a pH-responsive and sustained VCM release profile and in vitro antibacterial activity than non-coated niosomes and bare VCM. mPEG-OA-coated niosomes showed a significant reduction in biofilm formation at pH 6 compared to pH 7.4 ( p = 0,0119). The in vivo efficacy of mPEG-OA-coated niosomes in the BALB/c mice skin infection model showed a 9.9-fold reduction in MRSA load compared to bare VCM. Histomorphologically, the mPEG-OA-coated niosomes group displayed the lowest bacterial load, tissue swelling, and inflammation. The results of this study demonstrate the potential of novel pH-responsive mPEG-OA-derived polymer coating to enhance bacterial killing kinetics, and antibacterial and anti-biofilm efficacies over conventional antibiotic and non-functionalized nano delivery systems. more...