Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against Enterococcus faecalis in a Protozoa Infection Model

Abstract

Enterococcus faecalis ( E. faecalis ) biofilms are implicated in endocarditis, urinary tract infections, and biliary tract infections. Coupled with E. faecalis internalization into host cells, this opportunistic pathogen poses great challenges to conventional antibiotic therapy. The inability of ampicillin (Amp) to eradicate bacteria hidden in biofilms and intracellular niches greatly reduces its efficacy against complicated E. faecalis infections. To enhance the potency of Amp against different forms of E. faecalis infections, Amp was loaded into Lipid-Polymer hybrid Nanoparticles (LPNs), a highly efficient nano delivery platform consisting of a unique combination of DOTAP lipid shell and PLGA polymeric core. The antibacterial activity of these nanoparticles (Amp-LPNs) was investigated in a protozoa infection model, achieving a much higher multiplicity of infection (MOI) compared with studies using animal phagocytes. A significant reduction of total E. faecalis was observed in all groups receiving 250 μg/mL Amp-LPNs compared with groups receiving the same concentration of free Amp during three different interventions, simulating acute and chronic infections and prophylaxis. In early intervention, no viable E. faecalis was observed after 3 h LPNs treatment whereas free Amp did not clear E. faecalis after 24 h treatment. Amp-LPNs also greatly enhanced the antibacterial activity of Amp at late intervention and boosted the survival rate of protozoa approaching 400%, where no viable protozoa were identified in the free Amp groups at the 40 h postinfection treatment time point. Prophylactic effectiveness with Amp-LPNs at a concentration of 250 μg/mL was exhibited in both bacteria elimination and protozoa survival toward subsequent infections. Using protozoa as a surrogate model for animal phagocytes to study high MOI infections, this study suggests that LPN-formulated antibiotics hold the potential to significantly improve the therapeutic outcome in highly complicated bacterial infections.

Lipid-Coated Hybrid Nanoparticles for Enhanced Bacterial Biofilm Penetration and Antibiofilm Efficacy

“…In a more recent study, LCHNPs loaded with ampicillin were used to treat protozoa infected with Enterococcus faecalis in an intracellular infection model. When compared to unencapsulated ampicillin, the ampicillin-loaded LCHNPs were able to boost the survivability of protozoa cells by up to 400% while the release of ampicillin also significantly reduced the quantity of intracellular bacterial cells . While these prior studies explored the potential of LCHNPs in treating planktonic and intracellular bacterial infections, the potential of LCHNPs in treating biofilm infections remains unexplored.…”

Advances in Nanostructures for Antimicrobial Therapy

“…pH-responsive lipid polymer hybrid NPs (LPH NPs) co-loaded with vancomycin and 18β-glycyrrhetinic acid showing a size of 198.4 ± 0.3 nm and a zeta potential of −3.8 ± 0.335 mV exhibited sustained and faster release at acidic conditions and a 16-fold higher antibacterial effect against MRSA in vitro compared to free antibiotics, being able to eliminate 75% of MRSA in less than 12 h [ 152 ]. LPH NPs, with a 1,2-dioleoyl-3-trimethylammonium-propane lipid shell and polymeric PLGA core loaded with ampicillin considerably reduced total Enterococcus faecalis and boosted the survival rate of protozoa, the concentration 250 μg/mL being the most efficient, and they were effective not only in acute and chronic infections but also in prophylaxis [ 153 ]. Ceftriaxone-loaded LPH NPs consisting of CS, glycerol monostearate and polysorbate 80 as a stabilizer exhibited sustained drug release and showed an antibacterial effect against E. coli bacteria and were able to reduce the resistance of Enterococcus faecium bacteria in patients with cellulitis by 50% [ 154 ].…”

PLGA-Based Nanoplatforms in Drug Delivery for Inhibition and Destruction of Microbial Biofilm

“…These particles significantly suppressed the formation of the biofilm and preestablished biofilms in comparison to the fluconazole and free Juglone. 2021 (Tan et al, 2021) Ampicillin 194 nm size and 20.9 mv ZP Combination approach of emulsion solvent evaporation and lipid thin-film rehydration…”