title: PEGylated liposome encapsulation increases the lung tissue concentration of vancomycin.
abstract: Pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) often cannot be cured by vancomycin treatment. Poor lung tissue and intracellular penetration limits the ability to achieve effective bactericidal levels, particularly in alveolar macrophages, where MRSA can evade phagocytic killing. Compared to standard formulations, liposome encapsulation has been shown to enhance vancomycin intracellular killing of MRSA. In this murine pharmacokinetic and biodistribution study, PEGylated liposomal vancomycin, compared to standard and non-PEGylated formulations, significantly prolonged blood circulation time and increased deposition in lung, liver, and spleen and yet reduced accumulation in kidney tissue. As a result of optimizing antimicrobial targeting of infected lung tissue and limiting renal parenchymal exposure, administration of PEGylated liposomal vancomycin may improve the efficacy of treatment of MRSA pneumonia and reduce the risk of nephrotoxicity.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 E. 2nd Street, Pomona, CA 91766, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Muppidi
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wang
authors.forename: Guru
authors.initials: G
authors.lastname: Betageri
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Pumerantz
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D008081:Liposomes; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000382:microbiology; D011092:Polyethylene Glycols; D014018:Tissue Distribution; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D014640:Vancomycin