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Morphological studies on nanostructures for drug & gene delivery

B. Papahadjopoulos-Sternberg
NanoAnalytical Laboratory, UOP, Dental School, Microbiology Dept, US

Keywords: drug carrier, gene delivery, freeze-fracture electron microscopy

MORPHOLOGICAL STUDIES ON NANOSTRUCTURES FOR DRUG & GENE DELIVERY CARRIED OUT BY FREEZE-FRACTURE ELECTRON MICROSCOPY Brigitte Papahadjopoulos-Sternberg NanoAnalytical Laboratory & University of the Pacific, Dental School, Microbiology Dept., San Francisco, CA 94115 The potency of drug/gene-loaded carriers is frequently depending upon their morphology adopted in a biological relevant environment. Freeze-fracture electron microscopy/1/ is not only a powerful technique to characterize drug/gene carrier on a nanometer resolution scale/2,4-11/ but also the method of choice to study their fate related to drug/gene load, application milieu, and during interaction with cells/3,6,8/. Using freeze-fracture electron microscopy we studied the morphology of a wide variety of drug and gene carriers such as Multilamellar Vesicles (MLV, Fig. 1.1)/1,6/, Small Unilamellar Vesicles (SUV, Fig. 1.2)/1,6/, niosomes (Fig. 1.3) /5,6/, cochleate cylinder (Fig. 1.4) /6/, depofoam particles (Fig. 1.5), and cationic liposome/DNA complexes (CLDC, Fig. 2.1-3)/4,6-11/. While SUV are suitable for systemic applications, MLV are excellent depots for dermatological use. Cochleate cylinder are stable under acidic stomach conditions and therefore they are suitable for oral applications. Depending upon the type and ratio of the helper lipid CLDC are able to adopt spaghetti/meatball–type structure, map-pin, as well as honeycomb structures/4,6-11/. 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 structures/10,11/. References /1/ B. Sternberg In: Liposome Technology, 2nd Ed.: Liposome Preparation and related Techniques, ed G. Gregoriadis, CRC Press I, 363-383 (1992). /2/ K. Merz & B. Sternberg J. Drug Targeting 2 (1994) 411-417. /3/ K. Prüfer et al. J. Drug Targeting 2 (1994) 419-429. /4/ B. Sternberg et al. FEBS-Letters 356 (1994) 361-366 /5/ B. Sternberg et al. Nature 378 (1995) 21. /6/ B. Sternberg In: Handbook of Nonmedical Applications of Liposomes IV: From Gene Delivery and Diagnostics to Ecology, eds D. Lasic & Y. Barenholz, CRC Press (1996) 271-297. /7/ B. Sternberg J. Liposome Research 6 (1996) 515-533. /8/ B. Sternberg In: Medical Applications of Liposomes, Eds D. Lasic & D. Papahadjopoulos, Elsevier (1998) 395-427. /9/ O. Meyer et al. J. Biological Chemistry 273 (1998) 15621-15627. /10/ B. Sternberg et al. Biochim. Biophys. Acta 1375 (1998) 23-35. /11/ B. Sternberg et al. In: Targeting of Drugs 323: Strategies for Gene Constructs and Delivery, Eds G. Gregoriadis & B. McCormack, IOS Press (2000) 156-165.

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