The encapsulation of DNA molecules within biomimetic lipid nanocapsules.

Most of DNA synthetic complexes result from the self-assembly of DNA molecules with cationic lipids or polymers in an aqueous controlled medium. However, injection of such self-assembled complexes in medium like blood that differ from that of their formulation leads to strong instability. Therefore, DNA vectors that have physico-chemical properties and structural organisation that will not be sensitive to a completely different medium in terms of ionic and protein composition are actively sought. To this end, the goal here was to discover and optimize a nanostructured system where DNA molecules would be encapsulated in nanocapsules consisting in an oily core and a shell covered by PEG stretches obtained through a nanoemulsion process in the absence of organic solvent. This encapsulation form of DNA molecules would prevent interactions with external hostile biological fluid. The results show the entrapment of lipoplexes into lipid nanocapsules, leading to the formation of neutral 110 nm-DNA nanocapsules. They were weakly removed by the immune system, displaying an increased blood half-life, and improved carcinoma cell transfection, in comparison to the parent lipoplexes. Our results demonstrate that the fabrication of nanocapsules encapsulating hydrophilic DNA in an oily core that meet criteria for blood injection is possible.

[1]  P. B. Cowles.  Experimental Immunochemistry , 1948, The Yale Journal of Biology and Medicine.

[2]  R. Podgornik,et al.  The Structure of DNA−Liposome Complexes , 1997 .

[3]  J. Benoit,et al.  The influence of lipid nanocapsule composition on their size distribution. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[4]  R. Müller,et al.  The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. , 1995, Advanced drug delivery reviews.

[5]  H. Busscher,et al.  Characterization of poly(ethylene oxide) brushes on glass surfaces and adhesion of Staphylococcus epidermidis , 2003, Journal of biomaterials science. Polymer edition.

[6]  J. Benoit,et al.  Biodistribution of dual radiolabeled lipidic nanocapsules in the rat using scintigraphy and gamma counting. , 2002, International journal of pharmaceutics.

[7]  J. Benoit,et al.  Evaluation of pegylated lipid nanocapsules versus complement system activation and macrophage uptake. , 2006, Journal of biomedical materials research. Part A.

[8]  D. Devine,et al.  Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol)-lipids. , 1998, Archives of biochemistry and biophysics.

[9]  R. Juliano,et al.  Interactions of liposomes with the reticuloendothelial system. II: Nonspecific and receptor-mediated uptake of liposomes by mouse peritoneal macrophages. , 1982, Biochimica et biophysica acta.

[10]  J. Kreuter,et al.  Colloidal Drug Delivery Systems , 1994 .

[11]  C. Miller,et al.  Liposome-cell interactions in vitro: effect of liposome surface charge on the binding and endocytosis of conventional and sterically stabilized liposomes. , 1998, Biochemistry.

[12]  S. Moghimi,et al.  Capture of stealth nanoparticles by the body's defences. , 2001, Critical reviews in therapeutic drug carrier systems.

[13]  H. Harashima,et al.  Species Difference in the Disposition of Liposomes Among Mice, Rats, and Rabbits: Allometric Relationship and Species Dependent Hepatic Uptake Mechanism , 1996, Pharmaceutical Research.

[14]  Ohshima.  Dynamic Electrophoretic Mobility of a Soft Particle. , 2001, Journal of colloid and interface science.

[15]  F. Szoka,et al.  Effects of complement depletion on the pharmacokinetics and gene delivery mediated by cationic lipid-DNA complexes. , 1998, Human gene therapy.

[16]  D. Devine,et al.  Liposome-complement interactions in rat serum: implications for liposome survival studies. , 1994, Biochimica et biophysica acta.

[17]  Feng Liu,et al.  Antibody Dependent, Complement Mediated Liver Uptake of Liposomes Containing GM1 , 2004, Pharmaceutical Research.

[18]  J. M. Harris,et al.  LABORATORY SYNTHESIS OF POLYETHYLENE GLYCOL DERIVATIVES , 1985 .

[19]  J. Benoit,et al.  Electrokinetic properties of noncharged lipid nanocapsules: Influence of the dipolar distribution at the interface , 2005, Electrophoresis.

[20]  J. Ruysschaert,et al.  Formation and intracellular trafficking of lipoplexes and polyplexes. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[21]  J. Benoit,et al.  A Novel Phase Inversion-Based Process for the Preparation of Lipid Nanocarriers , 2002, Pharmaceutical Research.

[22]  D. Escande,et al.  Nonionic amphiphilic block copolymers promote gene transfer to the lung. , 2005, Human gene therapy.

[23]  D. Escande,et al.  A nonionic amphiphile agent promotes gene delivery in vivo to skeletal and cardiac muscles. , 2002, Human gene therapy.

[24]  Jean-Pierre Benoit,et al.  Parameters influencing the stealthiness of colloidal drug delivery systems. , 2006, Biomaterials.

[25]  K. Mechtler,et al.  Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. , 1996, Human gene therapy.

[26]  O. Bourdon,et al.  Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules. , 2001, Biomaterials.