Nano drug delivery system using green solvents: a novel safe promise for the treatment of infective endocarditis

Abstract Background Infective Endocarditis (IE) is a severe infection of the heart’s endocardial surface, with ~25% mortality. The global incidence exceeded 1 million cases in 2019. Staphylococcus, Streptococcus, and Enterococcus cause ~80% of cases, with S. aureus being most prevalent. Challenges in current IE treatments include antimicrobial resistance, poor biofilm penetration, and toxicity. Nanomedicine enables targeted drug delivery and addresses microbial resistance. Purpose This study develops a safe, effective nanodrug delivery system for IE management using Vancomycin-loaded PLGA nanoparticles (VAN-PLGA) formulated with green solvents and an FDA-approved polymer. The study focuses on Formulation & characterisation of VAN-PLGA,Efficacy assessment against 6 S. aureus strains via broth microdilution, agar well diffusion, and biofilm inhibition assays, and Cytotoxicity assessment on HUVECs, hVECs, and hVICs using MTT cytotoxicity and migration assays. Methods VAN-PLGA nanoparticles were synthesised via phase separation, where PLGA-COOH, PLGA-COOR, and PEG-PLGA were dissolved in Dimethyl Isosorbide (DMI) at 12%, with 20 mg vancomycin added and stirred followed by aqueous phase induced separation. Antimicrobial efficacy was tested via agar well diffusion (5–20 μg/mL), MIC/MBC, and biofilm inhibition assays (0.7–40 μg/mL). Cytotoxicity was assessed on HUVECs, hVECs, and hVICs at 0.5–160 μg/mL. Results VAN-PLGA nanoparticles (245.95 ± 2.05 nm, PDI 0.10 ± 0.04, Zeta Potential -4 ± 1.6 mV) were well-dispersed and spherical. Free vancomycin initially had higher antimicrobial activity, but VAN-PLGA exhibited sustained drug release, increasing inhibition zones after 72 hours, whereas free vancomycin plateaued at 48 hours. MIC and MBC values for VAN-PLGA were 2–3 times higher than those previously reported with organic solvents. VAN-PLGA inhibited biofilm formation by >80% at MBC and <50% at MIC, whereas free vancomycin inhibited >80% at MBC but <20% at MIC. Cytotoxicity assays confirmed >90% cell viability for VAN-PLGA, while free vancomycin significantly reduced viability (<50% at 20 μg/mL, <30% at 80 μg/mL). Wound healing was 90% for VAN-PLGA-treated HUVECs at 30 hours (160 μg/mL), compared to 40% for free vancomycin after 48 hours, proving VAN-PLGA’s superior safety and sustained antibacterial effect. Conclusion VAN-PLGA using green solvent is promising candidate for the management of IE and S. aureus infections. Unlike VAN-PLGA formulated with organic solvents, which showed >90% viability in carcinoma cell lines, VAN-PLGA demonstrated 90% cell viability on HUVECs, hVECs, and hVICs. this formulation demonstrated sustained drug release over 72 hours, resulting in T1/2 increase and dose frequency reduction. The MIC and MBC values recorded were higher than previously reported, proving enhanced antibacterial effects.SEM of VAN-PLGA using green solvents