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  • Title: Antimicrobial effectiveness of liposomal polymyxin B against resistant Gram-negative bacterial strains.
    Author: Alipour M, Halwani M, Omri A, Suntres ZE.
    Journal: Int J Pharm; 2008 May 01; 355(1-2):293-8. PubMed ID: 18164881.
    Abstract:
    Polymyxin B is a polycationic antibiotic effective in the treatment of Gram-negative bacterial infections. Systemic use of polymyxin B has been limited due to its toxicity, most notably nephrotoxicity, ototoxicity, and neuromuscular blockade. Entrapment of antibiotics in liposomes is known to enhance their antimicrobial activities while minimizing their toxic effects. In the present study, polymyxin B was incorporated into liposomes composed of either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (Chol) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and Chol. The entrapment efficiency of sonicated liposomes containing DPPC/Chol (32.1+/-2.43%) was six-fold higher than that of liposomes containing POPC/Chol (5.35+/-0.32%). On the other hand, the entrapment efficiency of extruded DPPC/Chol liposomes (3.23+/-0.46%) was about 30% less than that of liposomes composed of POPC/Chol (5.10+/-0.37%). Incubation of extruded DPPC/Chol liposomes containing polymyxin B in serum at 37 degrees C resulted in a complete release of the antibiotic into the supernatant after 3h as compared to 6h in the case of POPC/Chol liposomes. Spontaneous release of polymyxin B from DPPC/Chol liposomes incubated in saline was significantly higher (66%) than that from POPC/Chol liposomes (24%) after 48h at 37 degrees C. With respect to the antimicrobial activities of the liposomal polymyxin B formulations, the MICs of sonicated DPPC/Chol liposomes against Gram-negative strains were generally lower when compared to free polymyxin B. Immunocytochemistry and electron transmission microscopic studies revealed that the penetration of polymyxin B into a resistant strain of Pseudomonas aeruginosa was higher following its administration as a liposomal formulation as compared to its conventional form. The combination of free drug and plain liposomes had an antibacterial activity similar to that of free antibiotic. These data suggest that incorporation of polymyxin B in liposomes could be useful in the management of Gram-negative infections induced by these microorganisms.
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