Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2003 December; 4(4): 549–560.
Published online 2003 October 23. doi:  10.1208/pt040469
PMCID: PMC2750662

Unilamellar vesicles as potential capreomycin sulfate carriers: Preparation and physicochemical characterization


The aim of this work was to evaluate unilamellar liposomes as new potential capreomycin sulfate (CS) delivery systems for future pulmonary targeting by aerosol administration. Dipalmitoylphosphatidylcholine, hydrogenated phosphatidylcholine, and distearoylphosphatidylcholine were used for liposome preparation. Peptide-membrane interaction was investigated by differential scanning calorimetry (DSC) and attenuated total internal reflection Fourier-transform infrared spectroscopy (ATIR-FTIR). Peptide entrapment, size, and morphology were evaluated by UV spectrophotometry, photocorrelation spectroscopy, and transmission electron microscopy, respectively. Interaction between CS and the outer region of the bilayer was revealed by DSC and ATIR-FTIR. DSPC liposomes showed enhanced interdigitation when the CS molar fraction was increased. Formation of a second phase on the bilayer surface was observed. From kinetic and permeability studies, CS loaded DSPC liposomes resulted more stable if compared to DPPC and HPC over the period of time investigated. The amount of entrapped peptide oscillated between 10% and 13%. Vesicles showed a narrow size distribution, from 138 to 166 nm, and a good morphology. These systems, in particular DSPC liposomes, could represent promising carriers for this peptide.

Keywords: capreomycin sulfate, liposomes, DSC, ATIR-FTIR, phase transition

Full Text

The Full Text of this article is available as a PDF (510K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Maher D, Floyd K, Raviglione M. A strategic framework to decrease the burden of TB/HIV. WHO report, World Health Organization/ Communicable Disease/Tuberculosis, 2002; 296.
2. Vigorita MG, Ottana R, Zappalà C, Maccari R, Pizzimenti FC, Gabrielli G. Halogenated isoniazid derivatives as possible antimy cobacterial and anti-HIV agents-III. IL Farmaco. 1994;49:775–781. [PubMed]
3. Ferrarini P, Manera C, Mori C, Badawneh M, Saccomanni G. Synthesis and evaluation of antimycobacterial activity of 4-phenyl-1,8-naphthyridine derivatives. II Farmaco. 1999;53:741–746. doi: 10.1016/S0014-827X(98)00094-9. [PubMed] [Cross Ref]
4. Gursoy A. Liposome-encapsulated antibiotics: Physicochemical and antibacterial properties, a review. STP Pharma Sci. 2000;10(4):285–291.
5. Deol P, Khuller GK. Lung specific stealth liposomes: stability, biodistribution and toxicity of liposomal antitubercular drugs in mice. Biochim Biophys Acta. 1997;1334:161–172. [PubMed]
6. Pinto-Alphandary H, Andremont A, Couvreur P. Targeted delivery antibiotics using liposomes and nanoparticles: research and applications. Int J Antimicrob Agents. 2000;13:155–168. doi: 10.1016/S0924-8579(99)00121-1. [PubMed] [Cross Ref]
7. Le Conte P, Le Gallou F, Potel G, Struillou L, Baron D, Drugeon HB. Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminatedMycobacterium avium beige mouse model. Antimicrob Agents Chemother. 1994;38:2695–2701. [PMC free article] [PubMed]
8. Martindale the Extra Pharmacopoeia . Capreomycin sulfate (7554-1) In: Parfitt K, editor. The Complete Drug Reference—Monographs. 3 2nd ed. London, UK: The Pharmaceutical Press; 1997. pp. 162–162.
9. Fattorini L, Iona E, Ricci ML, Thoresen OF, Orru G, Oggioni MR, Tortoli E, Piersimoni C, Chiaradonna P, Tronci M, Pozzi G, Orefici G. Activity of 16 antimicrobial agents against drug-resistant strains of Mycobacterium tuberculosis. Microb Drug Resist. 1999;5:265–270. doi: 10.1089/mdr.1999.5.265. [PubMed] [Cross Ref]
10. Farr SJ, Kellaway IW, Perry-Jones DR, Woolfrey SG. 99-m Technetium as a marker of liposomal deposition and clearance in the human lung. Int J Pharm. 1985;26:303–316. doi: 10.1016/0378-5173(85)90239-X. [Cross Ref]
11. Gilbert BE, Six HR, Wilson SZ, Wyde PR, Knight V. Small particle aerosols of enviroxime-containing liposomes. J Antiviral Res. 1988;9:355–365. doi: 10.1016/0166-3542(88)90037-X. [PubMed] [Cross Ref]
12. Niven RW, Schreier H. Nebulization of liposomes, I: effects of lipid composition. Pharm Res. 1990;7:1127–1133. doi: 10.1023/A:1015924124180. [PubMed] [Cross Ref]
13. Schreier H, Gonzalez-Rothi RJ, Steceko AA. Pulmonary delivery of liposomes. J Control Release. 1993;24:209–223. doi: 10.1016/0168-3659(93)90180-D. [Cross Ref]
14. Taylor KMG, Farr SJ. Liposomes for delivery to the respiratory tract. Drug Dev Ind Pharm. 1993;19:123–142. doi: 10.3109/03639049309038764. [Cross Ref]
15. Hung OR, Whynot SC, Varnel JR, Shafer SL, Mezel M. Pharmacokinetics of inhaled liposome encapsulated fentanyl. Anesthesiology. 1995;83:277–284. doi: 10.1097/00000542-199508000-00007. [PubMed] [Cross Ref]
16. Patton JS, Platz RM. Pulmonary delivery of peptides and proteins for systemic action. Adv Drug Deliv Rev. 1992;8:179–196. doi: 10.1016/0169-409X(92)90002-8. [Cross Ref]
17. Niven RW, Speer M, Schreier H. Nebulization of liposomes, II: the effects of size and modelling of solute release profiles. Pharm Res. 1991;8(2):217–221. doi: 10.1023/A:1015896121377. [PubMed] [Cross Ref]
18. Mayer LD, Hope MJ, Cullis PR. Vesicles of variable, sizes produced by a rapid extrusion procedure. Biochim Biophys Acta. 1986;858:161–168. doi: 10.1016/0005-2736(86)90302-0. [PubMed] [Cross Ref]
19. Sivakuma PA, Panduranga KR. Development of stable polymerized vinyl-pyrrolidone cholesteryl methacrylate liposomes as carriers for drug delivery. Biomed Microdev. 2002;4(3):197–204. doi: 10.1023/A:1016096329874. [Cross Ref]
20. Moscho A, Orwar O, Chiu DT, Modi BP, Zare RN. Rapid preparation of giant unilamellar vesicles. Proc Natl Acad Sci USA. 1996;93:11443–11447. doi: 10.1073/pnas.93.21.11443. [PubMed] [Cross Ref]
21. Goormaghtigh E, Raussens V, Ruysschaert JM. Attenuated total reflection infrared spectroscopy of proteins and lipids in biological membranes. Biochim Biophys Acta. 1999;1422:105–185. [PubMed]
22. Jain MK. Order and dynamics in bilayers and solute in bilayers. In: Jain MK, editor. Introduction to Biological Membranes. New York, NY: Wiley; 1988. pp. 122–165.
23. Taylor KMG, Morris RM. Thermal analysis of phase transition behaviour in liposomes. Thermochim Acta. 1995;248:289–301. doi: 10.1016/0040-6031(94)01884-J. [Cross Ref]
24. Weers JG, Scheuing DR. Characterization of viscoelatic surfactant mixtures, I: Fourier transform infrared spectroscopic studies. Colloids Surf. B: Biointerfaces. 1991;55:41–56.
25. Fringeli UP, Guenthard HH. Infrared membrane spectroscopy. Mol Biol Biochem Biophys. 1981;31:270–332. [PubMed]
26. Guenzler H, Boeck H. IR Spectroscopy. An Introduction. 2nd ed. Weinheim, Germany: Verlag Chemie; 1983. pp. 403–403.
27. Silvestro L, Axelsen PH. Infrared spectroscopy of supported lipid monolayer, bilayer, multibilayer membranes. Chem Phys Lipids. 1998;96:69–80. doi: 10.1016/S0009-3084(98)00081-4. [PubMed] [Cross Ref]
28. Attar M, Wong PTT, Kates M, Carrier D, Jaklis P, Tanphaichitr N. Interaction between sulfogalactosylceramide and dimyristoylphosphatidylcholine increases the orientational fluctuation of their lipid hydrocarbon chains. Chem Phys, Lipids. 1998;94:227–238. doi: 10.1016/S0009-3084(98)00057-7. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists