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- W2092108820 abstract "The stability of nonviral vectors during freeze-drying has been well-studied, and it has been established that sugars can protect lipoplexes during freeze-drying. However low levels of damage are often observed after freeze-drying, and this damage is more evident in dilute lipoplex preparations. By investigating the stability of lipoplexes after each step in the freeze-drying cycle (i.e., freezing, primary drying, and secondary drying), we strive to understand the mechanisms responsible for damage and identify improved stabilization strategies. N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP)–cholesterol/plasmid DNA lipoplexes were prepared at an equimolar DOTAP–cholesterol ratio, and a 3:1 DOTAP+–DNA− charge ratio. Our experiments indicate that despite sufficient levels of “stabilizing” sugars, significant damage is still evident when dilute lipoplex preparations are subjected to freeze-drying. Analysis of the different stages of freeze-drying suggests that significant damage occurs during freezing, and that sugars have a limited capacity to protect against this freezing-induced damage. Similar effects have been observed in studies with proteins, and surfactants have been employed in protein formulations to protect against surface-induced damage, for example, at the ice crystal, solid, air, or sugar glass surfaces. However, the use of surfactants in a lipid-based formulation is inherently risky due to the potential for altering/solubilizing the lipid delivery vehicle. Our data indicate that judicious use of surfactants can reduce surface-induced damage and result in better preservation of lipoplex size and transfection activity after freeze-drying. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3319–3328, 2009" @default.
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- W2092108820 date "2009-09-01" @default.
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- W2092108820 title "Synergistic effects of surfactants and sugars on lipoplex stability during freeze-drying and rehydration" @default.
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- W2092108820 doi "https://doi.org/10.1002/jps.21564" @default.
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