Preparation of liposomal vancomycin and intracellular killing of meticillin-resistant Staphylococcus aureus (MRSA).
Meticillin-resistant Staphylococcus aureus (MRSA) can persist in alveolar macrophages and contribute to clinical failure of intravenous vancomycin to cure pneumonia. In this study, it was shown that vancomycin in standard solution is unable to kill intracellular MRSA within macrophages. The intracellular viability of MRSA inside macrophages treated with two different formulations of encapsulated liposomal vancomycin prepared using a hydration-dehydration method was then determined. In contrast to the observations with standard vancomycin, treatment with conventional non-pegylated liposomal vancomycin (lacking any surface modification) resulted in a sufficient concentration of antibiotic inside the intracellular compartment of the macrophages to exert a marked bactericidal effect against MRSA. On the other hand, treatment of infected macrophages with surface-pegylated liposomes resulted in no impact on MRSA survival, and this lack of an inhibitory effect may likely reflect delayed phagocytosis owing to the 'stealth' effect by pegylation. This study indicates the potential for a novel liposomal delivery system that may improve clinical vancomycin treatment outcomes by targeting intracellular MRSA infection.
Department of Internal Medicine, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA. apumerantz@westernu.edu
Andrew
A
Pumerantz
Krishna
K
Muppidi
Sunil
S
Agnihotri
Carlos
C
Guerra
Vishwanath
V
Venketaraman
Jeffrey
J
Wang
Guru
G
Betageri
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D003593:Cytoplasm / Q000737:chemistry; D004337:Drug Carriers / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D050296:Microbial Viability / Q000187:drug effects; D014640:Vancomycin / Q000493:pharmacokinetics / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008081:Liposomes; D014640:Vancomycin