Combating Intracellular Pathogens with Nanohybrid-Facilitated Antibiotic Delivery

• Published in: International journal of nanomedicine Vol. 15; pp. 8437 - 8449
• Main Authors: Bose, Rajendran J C, Tharmalingam, Nagendran, Choi, Yonghyun, Madheswaran, Thiagarajan, Paulmurugan, Ramasamy, McCarthy, Jason R, Lee, Soo-Hong, Park, Hansoo
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antibiotics; Aqueous solutions; Bacteria; Bacterial infections; Biomedical engineering; Cell Line; Cell Survival - drug effects; Cytotoxicity; doxycycline; Drug Delivery Systems; Drug Liberation; Efficiency; intracellular bacterial infection; Intracellular Space - microbiology; Lipids; Lipids - chemistry; Macrophages; Macrophages - drug effects; Macrophages - microbiology; Medical imaging equipment; Methicillin; Mice; Microbial Sensitivity Tests; Microscopy; Murder; mycobacterium smegmatis; Mycobacterium smegmatis - drug effects; nanohybrids; Nanomaterials; Nanoparticles; Nanoparticles - chemistry; Original Research; Particle Size; Polyethylene glycol; Polymers; Polymers - chemistry; Polyvinyl alcohol; Staphylococcal infections; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus infections; Surface active agents; vancomycin; Vancomycin - pharmacology; South Korea; United States > US; Japan; Germany; Mycobacterium smegmatis; intracellular bacterial infection; vancomycin; doxycycline; nanohybrids; Staphylococcus aureus
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S271850

Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell-nanoparticle interactions, and consequently how it influences the cytological response, is in high demand. Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against or infected macrophages. The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls. In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications.