Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 97, Issue 7, Pages 2691-2701Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.21201
Keywords
solid-state NMR; FTIR; calorimetry DSC; phospholipid liposomes; drug delivery; encapsulation; bilayer; chloramphenicol; Staphylococcus aureus; eye infection
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Since their discovery by Bangham and coworkers almost four decades ago, liposomes have become models for biomembranes and vehicles for pharmaceutical, diagnostic, and cosmetic agents. One of the advantages of using liposomes as a drug vehicle is their ability for slow release, thus reducing dosage, localizing a drug, and minimizing its side-effects. Antibiotic resistance is a growing global problem, including for ocular bacterial infection by Staphylococcus aureus, where time is an important parameter that determines the severity of infection. This situation has prompted the pursuit of ways to prepare drug-encapsulating liposomes that enable bulk release of the drug chloramphenicol (CAP) once the liposomal structure is perturbed. Our approach is a two-step process: first, to characterize the interaction of CAP with model biomembranes of dimyristoylphosphatidylcholine (DMPC) used to prepare CAP-liposomes by different formulations; second, to test the efficiency of these formulation against S. aureus. Solid-state NMR, differential scanning calorimetry, and infrared spectroscopy were used to study the interaction of CAP with DMPC bilayers. The minimum inhibitory concentrations and time-kill curves for S. aureus using different liposomal preparations were compared. Evidence of conformational changes in the DMPC molecules and the effectiveness of the CAP encapsulated in liposomes are reported. (C) 2007 Wiley-Liss, Inc.
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