A nanoscale polynucleotide-neutral liposome self-assemblies formulated for therapeutic gene delivery
- Autores: Erhan Süleymanoglu
- Localización: Revista Electrónica de Biomedicina, ISSN-e 1697-090X, Nº. 2, 2004, págs. 13-35
- Idioma: varios idiomas
- Enlaces
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Resumen
Human gene therapy research is currently discouraging due to the lack of suitable delivery vehicles for nucleic acid transfer to affected cell types. There is an urgent need for optimized gene delivery tools capable of protecting the polynucleotide from degradation through its route from site of administration to gene expression.
Besides difficulties arising during the preparation of the currently employed cationic lipids, their cytotoxicity has been an unavoidable hurdle. Some energetics issues related to preparation and use of self-assemblies formed between neutral lipid and polynucleotides with various conformation and size are presented.
The divalent metal cation-governed adsorption, aggregation and adhesion between single- and double-stranded polynucleotides with multilamellar and unilamellar phosphatidylcholine vesicles was followed turbidimetrically.
Thermotropic phase transitions of zwitterionic liposomes and their complexes with polynucleotides and calf thymus DNA with Ca2+ and Mg2+ is presented and compared to the previous data for various electrostatic lipid - nucleic acid complexes.
Differential scanning microcalorimetric measurements of synthetic phosphatidylcholine vesicles and polynucleotides and their ternary complexes with inorganic cations were used to build the thermodynamic model of their structural transitions. The increased thermal stability of the phospholipid bilayers is achieved by affecting their melting transition temperature by nucleic acid induced electrostatic charge screening.
Thermodynamic measurements give evidence for the stabilization of polynucleotide helices upon their association with liposomes in presence of divalent metal cations. It is thus possible to suggest this selfassembly as an improved formulation with further potential in gene therapy trials. Although the pharmacodynamical features of the zwitterionic lipid-metal ion-DNA nanocondensates remain to be tested in further transfection experiments, at least from physicochemical viewpoint, stability parameters are encouraging to consider them as a promising metal-based nucleic acid pharmaceuticals.
