PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of pharmscispringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSci. Dec 2003; 5(4): 62–76.
Published online Nov 18, 2003. doi:  10.1208/ps050430
PMCID: PMC2750992
Lipid-based supramolecular systems for topical application: A preformulatory study
Elisabetta Esposito,corresponding author1 Nadia Eblovi,1 Silvia Rasi,2 Markus Drechsler,3 Giordano M. Di Gregorio,4 Enea Menegatti,1 and Rita Cortesi1
1Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara, 19, I-44100 Ferrara, Italy
2Institute für Polymere, ETH Zentrum, Zürich, Switzerland
3Macromolecular Chemistry II, University of Bayreuth, Germany
4Dipartimento di Scienze Applicate ai Sistemi Complessi e INFM, Università Politecnica delle Marche, Ancona, Italy
Elisabetta Esposito, Phone: +39-0532-291259, Fax: +39-0532-291296, ese/at/unife.it.
corresponding authorCorresponding author.
Received April 18, 2003; Accepted September 22, 2003.
This article describes the production and characterization of monoglyceride-based supramolecular systems by a simple processing technique, avoiding time-consuming procedures, high energy input, and the use of organic solvents. A preformulatory study was performed to study the influence of the experimental parameters on the production of monoglyceride-based disperse systems. In particular the effects of (1) stirring speed, (2) type and concentration of monoglyceride mixture, and (3) type and concentration of surfactant were investigated on the recovery, fraction of larger particles, mean diameter, and shape of smaller particles (so called nanosomes). Dispersions were first characterized by optical microscopy and freeze-fracture electron microscopy. The mean diameter of standard nanosomes, analyzed by photon correlation spectroscopy (PCS) after elimination of larger particles by filtration, was 193.5 nm. Cryotransmission electron microscopy studies, conducted in order to investigate the structure of dispersions, showed the coexistence of vesicles and particles characterized by a cubic organization. X-ray diffraction data revealed the coexistence of 2 different cubic phases, the first being a bicontinuous cubic phase of spatial symmetry Im3m (Q229) and the second belonging to the Pn3m spatial symmetry. A study on the stability of monoglyceride-based dispersions based on macroscopical analysis of organoleptic properties and dimensional analysis by time was performed after elimination of larger particles by filtration. Organoleptic and morphological features do not change by time, appearing free from phase-separation phenomena for almost 1 year from production. PCS studies showed that nanosomes undergo an initial increase in mean diameter within the first month following production; afterwards they generally maintain their dimensions for the next 4 months.
Keywords: monoglycerides, nanosome dispersions, photon correlation spectroscopy
1. Thormar H, Isaacs CE, Brown HR, Barshatzy MR, Pessolano T. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother. 1987;31:27–31. [PMC free article] [PubMed]
2. Thormar H, Isaacs CE, Kim KS, Brown HR. Inactivation of visna virus and other enveloped viruses by free fatty acids and monoglycerides. Ann N Y Acad Sci. 1994;724:465–471. doi: 10.1111/j.1749-6632.1994.tb38948.x. [PubMed] [Cross Ref]
3. Isaacs CE, Litov RE, Thormar H. Antimicrobial activity of lipids added to human milk, infant formula and bovine milk. Nutr Biochem. 1995;6:362–366. doi: 10.1016/0955-2863(95)80003-U. [PubMed] [Cross Ref]
4. Kristmundsdottir T, Amadottir SG, Bergsson G, Thormar H. Development and evaluation of microbicidal hydrogels containing monoglyceride as the active ingredient. J Pharm Sci. 1999;88:1011–1015. doi: 10.1021/js9900396. [PubMed] [Cross Ref]
5. Isaacs CE, Kim KS, Thormar H. Inactivation of enveloped viruses in human bodily fluids by purified lipids. Ann N Y Acad Sci. 1994;724:457–464. doi: 10.1111/j.1749-6632.1994.tb38947.x. [PubMed] [Cross Ref]
6. D'Antona P, Parker WO, Zanirato MC, Esposito E, Nastruzzi C. Rheologic and NMR characterization of monoglyceride-based formulation. J Biomed Mat Res. 2000;52:40–52. doi: 10.1002/1097-4636(200010)52:1<40::AID-JBM6>3.0.CO;2-V. [PubMed] [Cross Ref]
7. Hyde ST, Andersson S, Ericsson B, Larsson K. A cubic structure consisting of a lipid bilayer forming an infinite periodic minimal surface of the gyroid type in the glycerol monooleate water system. Z Kristallogr. 1984;168:213–219.
8. Chung H, Caffrey M. The neutral area surface of the cubic mesophases: location and properties. Biophys J. 1994;66:377–381. [PubMed]
9. Engstroem S, Lindahl L, Wallin R, Engblom J. A study of polar lipid drug carrier systems undergoing a thermoreversible lamellar-to-cubic phase transition. Int J Pharm. 1992;86:137–145. doi: 10.1016/0378-5173(92)90190-D. [Cross Ref]
10. Engstroem S, Norden TP, Nyquist H. Cubic phases for studies of drug partition into lipid bilayers. Eur J Pharm. 1999;8:243–254. doi: 10.1016/S0928-0987(99)00012-3. [PubMed] [Cross Ref]
11. Shah JC, Sadhale Y, Chilukuri DM. Cubic phase gels as drug delivery systems. Adv Drug Deliv Rev. 2001;47:229–250. doi: 10.1016/S0169-409X(01)00108-9. [PubMed] [Cross Ref]
12. Larsson K. Aqueous dispersion of cubic lipid-water phases. Curr Opin Colloid In. 2000;5:64–69. doi: 10.1016/S1359-0294(00)00040-6. [Cross Ref]
13. Engstrom S, Ericsson B, Landh T. A cubosome formulation for intravenous administration of somatostatin. Proc Int Symp Control Rel Bioact Mater. 1996;23:382–383.
14. Kim JS, Kim HK, Chung H, Sohn YT, Kwon IC, Jeong SY. Drug formulations that form a dispersed cubic phase when mixed with water. Proc Int Symp Control Rel Bioact Mater. 2000;27:1118–1119.
15. Chung H, Kim J, Um JY, Kwon IC, Jeong SY. Self-assembled “nanocubicle” as a carrier for peroral insulin delivery. Diabetologia. 2002;45(3):448–451. doi: 10.1007/s00125-001-0751-z. [PubMed] [Cross Ref]
16. Landh T, Larsson K, inventors; GS Development AB, SE, assignee. Particles, method of preparing said particles and uses thereof. Canadian Patent WO93/06921. April 15, 1993.
17. Gustafsson J, Ljusberg-Wharen H, Almgrem M, Larsson K. Submicronparticles of reversed lipid phases in water stabilized by a nonionic amphiphilic polymer. Langmuir. 1997;13:6964–6971. doi: 10.1021/la970566+. [Cross Ref]
18. Siekmann B, Bunjes H, Koch MHJ, Westesen K. Preparation and structural investigations of colloidal dispersions prepared from cubic monoglyceride-water phases. Int J Pharm. 2002;244:33–43. doi: 10.1016/S0378-5173(02)00298-3. [PubMed] [Cross Ref]
19. Spicer PT, Hayden KL. Novel process for producing cubic liquid cristalline nanoparticles (cubosomes) Langmuir. 2001;17:5748–5756. doi: 10.1021/la010161w. [Cross Ref]
20. Nakano M, Sugita A, Matsuoka H, Handa T. Small angle x-ray scattering and 13C NMR investigation on the internal structure of “cubosomes” Langmuir. 2001;17:3917–3922. doi: 10.1021/la010224a. [Cross Ref]
21. Arshady R. Albumin microspheres and microcapsules: methodology of manufacturing techniques. J Control Release. 1990;14:111–131. doi: 10.1016/0168-3659(90)90149-N. [Cross Ref]
22. Almgrem M, Edwards K, Karlsson G. Cryo transmission electron microscopy of liposomes and related structures. Colloid Surface A. 2000;174:3–21. doi: 10.1016/S0927-7757(00)00516-1. [Cross Ref]
23. Gustafsson J, Ljusberg-Wharen H, Almgrem M, Larsson K. Cubic lipid-water phase dispersed into submicron particles. Langmuir. 1996;12:4611–4613. doi: 10.1021/la960318y. [Cross Ref]
24. Lee SC, Oh JT, Jang MH, Chung SI. Quantitative analysis of polyvinylalcohol on the surface of poly(D,L-lactide-co-glycolide) microparticles prepared by solvent evaporation method: effect of particle size and PVA concentration. J Control Release. 1999;59:123–132. doi: 10.1016/S0168-3659(98)00185-0. [PubMed] [Cross Ref]
25. Baras B, Benoit MA, Gillard J. Parameters influencing the antigen release from spray-dried poly(DL-lactide) microparticles. Int J Pharm. 2000;200(1):133–145. doi: 10.1016/S0378-5173(00)00363-X. [PubMed] [Cross Ref]
26. Lemoine D, Preat V. Polymeric nanoparticles as delivery system for influenza virus glycoproteins. J Control Release. 1998;54:15–27. doi: 10.1016/S0168-3659(97)00241-1. [PubMed] [Cross Ref]
27. Cavalier M, Benoit JP, Thies C. The formation and characterization of hydrocortisone-loaded poly(+/−)-lactide) microspheres. J Pharm Pharmacol. 1986;38(4):249–253. [PubMed]
28. Caboi F, Amico GS, Pitzalis P, Monduzzi M, Nylander T, Larsson K. Addition of hydrophilic and lipophilic compounds of biological relevance to the monoolein/water system. I. Phase behavior. Chem Phys Lipids. 2001;109(1):47–62. doi: 10.1016/S0009-3084(00)00200-0. [PubMed] [Cross Ref]
29. Wörle G, Westesen K, Koch MHJ. EMBL Hamburg Outstation Annual Report. Heidelberg, Germany: European Molecular biology Laboratory; 2000. Investigation of the phase behavior of monoolein/surfactant dispersions of different composition and preparation methods.
30. Mariani P, Luzzati V, Delacroix H. Cubic phases of lipid-containing systems. Structure analysis and biological implications. J Mol Biol. 1988;204:165–189. doi: 10.1016/0022-2836(88)90607-9. [PubMed] [Cross Ref]
31. Luzzati V, Vargas R, Mariani P, Gulik A, Delacroix H. Cubic phases of lipid-containing systems. Elements of a theory and biological connotations. J Mol Biol. 1993;229(2):540–551. doi: 10.1006/jmbi.1993.1053. [PubMed] [Cross Ref]
32. Johnsson M, Edwards K. Phase behavior and aggregate structure in mixtures of dioleoylphosphatidylethanolamine and poly(ethylene glycol)-lipids. Biophys J. 2001;80:313–323. [PubMed]
33. Templer RH, Seddon JM, Warrender NA, et al. Inverse Bicontinuous cubic phases in 2[ratio]1 fatty acid/phosphatidylcholine mixtures. The effects of chain length, hydration, and temperature. J Phys Chem. 1998;102:7251–7261.
Articles from AAPS PharmSci are provided here courtesy of
American Association of Pharmaceutical Scientists