Technological Aspects of Scalable Processes for the Production of Functional Liposomes for Gene Therapy

摘要: The success of gene delivery systems in vivo or vitro applications depends on efficient transfection. Cationic liposomes remain a promising alternative for nonviral DNA carriers, mainly because they protect from interstitial fluids and easily interact with cells (Gregoriadis, 1993; Lasic, 1997). However, order to be effective the immunological response, cationic must functional reach their specific target. Stability, reduced toxicity, efficiency delivering genes cells, targeting nucleus are essential requirements prophylactic and/or therapeutic performance. In achieve these standards, important physico-chemical parameters controlled, such as functionality lipids, concentration lipid, loading (reflected by R+/molar charge ratio), zeta potential, size, polydispersity. Several laboratory experiments have already explored vaccines using lipids. A classical investigation lipid composition, well was performed Perrie colleagues (Perrie & Gregoriadis, 2000; et al., 2001). plasmid pRc/CMV HBS encoding S (small) region hepatitis B surface antigen encapsulated dehydrated-hydrated composed egg phosphatidylcholine (EPC, bilayer-forming lipid), 1,2-dioleoyl-3trimethylammonium-propane (DOTAP, 1,2-dioleoyl-sn-glycero-3phosphoethanolamine (DOPE, helper lipid) 50:25:25 percent molar ratio. authors demonstrated that encapsulation process protects vaccine against incubation sodium dodecyl sulfate (SDS) due incorporation inside liposome lamella 2000), better response obtained compared naked DNA. Concerning size polydispersity, different reported nanoparticle is an parameter transfection (Ma 2007; Ogris 1998; Rejman 2004; Ross Hui, 1999; Wiewrodt 2002). Indeed, most variability procedures consequence non-viral high polydispersity index values. related width particle