Liposome-based formulations for the antibiotic nonapeptide Leucinostatin A: Fourier transform infrared spectroscopy characterization and in vivo toxicologic study.
Leucinostatin-A is a nonapeptide isolated from Paecilomyces marquandii, Paecilomyces lilacinus A257, and Acremonium sp., exerting remarkable phytotoxic, antibacterial (especially against Gram-positive) and antimycotic activities. With the aim to find alternative formulation for in vivo administration, a number of Leucinostatin-A-loaded liposomal formulations have been prepared and characterized. Both large unilamellar vesicles and multilamellar vesicles consisting of synthetic and natural lipids were evaluated. In addition, to determine the nature of peptide-membrane interactions and the stability of liposomes loaded with Leucinostatin-A, a Fourier Transform Infrared Spectroscopy study was performed. The results suggest that the mode of interaction of the peptide is dependent on its concentration, on bilayer fluidity, and on liposome type. Finally, the LD50 of both free and liposome-delivered Leucinostatin-A was determined in mice. These results suggest that the incorporation of Leucinostatin-A into liposomes may result in decreased Leucinostatin-A toxicity, as the intraperitoneal administration of Leucinostatin-A-loaded liposomes reduced the LD50 of Leucinostatin-A 15-fold.
Ricci
M
M
Institute of Chimica e Tecnologia del Farmaco, in Department of Chimica e Tecnologia, Università degli Studi, 06123 Perugia, Italy. riky@unipg.it
Sassi
P
P
Nastruzzi
C
C
Rossi
C
C
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000633:toxicity; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000633:toxicity; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007928:Lethal Dose 50; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000737:chemistry* / Q000633:toxicity*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013816:Thermodynamics; D023382:Toxicity Tests, Acute / Q000379:methods
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D010455:Peptides; C008268:leucinostatin A