COLL 3 |
| Brigitte Papahadjopoulos-Sternberg, Dental School, Microbiology Department, Dental School, Microbiology Department, Nanoanalytical Laboratory & University of the Pacific, 3951 Sacramento Street, San Francisco, CA 94118 |
| The potency of drug/gene-loaded carriers is frequently depending upon their morphology adopted in a biological relevant environment. Freeze-fracture electron microscopy is not only a powerful technique to characterize drug/gene carrier at nanometer resolution scale but also the method of choice to study their fate related to drug/gene load, application milieu, and during interaction with cells[1-3]. Using freeze-fracture electron microscopy we studied the morphology of a wide variety of drug and gene carriers such as depofoam particles, cochleate cylinder, liposomes, niosomes, micelles, and cationic liposome/DNA complexes. Furthermore we correlated the morphology of CLDC to their transfection activity under in vitro as well as in vivo conditions. While MLV display a multitude of bilayers and diameters of several micrometers, SUV have only one bilayer and can be as small as 15 nm[1-4]. Because of their small size (5-50 nm), spherical micelles accumulate in pathological areas and are excellent carrier for poorly water soluble drugs [5]. Niosomes are able to adopt geodetic sphere structure[6]. Cochleate cylinders are made of negatively charged lipids and form cigar-like cylinders several tens of micrometers long[1,2]. DepoFoam particles are prepared by double emulsification processes and display chambered inner volumes several tens of micrometers large. Depending upon helper lipid, ionic strength, and gene component CLDC adopt polymorph structures such as spaghetti/meatballs, map-pins, as well as honeycomb structures [7,8]. Parallel studies of transfection activity and morphology of CLDC revealed a fundamental difference between in vitro and in vivo transfection activity. Lipid precipitates displaying honeycomb structure are associated with high transfection rates under in vitro conditions. In vivo transfection activity seems to be associated with small complexes such as map-pin structure [8]. References: [1] B.Sternberg, Liposome Technology, CRC Press I (1992) 363. [2] B.Sternberg, Handbook Nonmed. Applications of Liposomes CRC Press (1996) 271. [3] B.Sternberg, Medical Applications of Liposomes, Elsevier (1998) 395. [4] V.P.Torchilin et al. PNAS (2003) 100 (4) 1972. [5] V.P.Torchilin et al. PNAS (2003) 100 (10) 603. [6] B.Sternberg et al., Nature 378 (1995) 21. [7] B.Sternberg et al., FEBS-Letters 356 (1994) 361. [8] B.Sternberg et al., Biochim. Biophys. Acta 1375 (1998) 1375. |
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Bio-Colloids
8:30 AM-11:30 AM, Sunday, March 28, 2004 Marriott -- Grand Ballroom J, Oral
Division of Colloid and Surface Chemistry |