An emergent class of molecules with potential therapeutic value for a variety of socially relevant human diseases is represented by the so called Nucleic Acid Based Drugs (NABD), including small interfering RNAs (siRNA), decoy oligodeoxynucleotides (decoy ODN) and antisense oligonucleotides (ASOs). Although NABD can be engineered to be specifically directed against virtually any target, their instability and poor delivery into target tissues severely limits their therapeutic use and requires the development of nanoscale delivery systems [1]. For delivery of NABD, Inulin (Inu), a natural, water soluble and biocompatible polysaccharide, was derivatized by Spermine (Spm), a flexible molecule with four amine groups that, having pKa values in the range between 8-11, is mainly in the protonated form at pH 7.4.The synthesis of related copolymers (Inu- Spm) was performed by a two step reaction, using an alternative method for performing organic reactions, named Enhanced Microwave Synthesis (EMS) [2,3]. By externally cooling the reaction vessel with compressed air, while simultaneously administering microwave irradiation, more energy can be directly applied to the reaction mixture. The synthesized inulin derivatives were characterized by FT-IR spectra and 1H-NMR. These polycations were tested to evaluate their ability to form non covalent complexes with genetic material (polyplexes). Agarose gel retardation assays showed that the obtained copolymers effectively condensed both plasmid DNA and DNA duplex to form polyplexes at different c/p weight ratios. Moreover, light scattering studies, performed to analyze size and z-potential of polyplexes, evidenced that copolymers are able to interact with genetic material leading to the formation of nanoscale systems. In addiction, biocompatibility of poliplexes was demonstrated by performing citotoxicity assays on a 16HBE cell line. [1] Current Signal Trasduction Therapy, 2010, (5): 92-120 [2] World Patent WO 04002617, January 8, 2004 [3] Aldrichimica Acta, 2004, (37): 66-76.
Inulin cationic derivatives obtained via enhanched microwave synthesis for nucleic acid based drugs delivery
Sardo C;Cavallaro G;
2012
Abstract
An emergent class of molecules with potential therapeutic value for a variety of socially relevant human diseases is represented by the so called Nucleic Acid Based Drugs (NABD), including small interfering RNAs (siRNA), decoy oligodeoxynucleotides (decoy ODN) and antisense oligonucleotides (ASOs). Although NABD can be engineered to be specifically directed against virtually any target, their instability and poor delivery into target tissues severely limits their therapeutic use and requires the development of nanoscale delivery systems [1]. For delivery of NABD, Inulin (Inu), a natural, water soluble and biocompatible polysaccharide, was derivatized by Spermine (Spm), a flexible molecule with four amine groups that, having pKa values in the range between 8-11, is mainly in the protonated form at pH 7.4.The synthesis of related copolymers (Inu- Spm) was performed by a two step reaction, using an alternative method for performing organic reactions, named Enhanced Microwave Synthesis (EMS) [2,3]. By externally cooling the reaction vessel with compressed air, while simultaneously administering microwave irradiation, more energy can be directly applied to the reaction mixture. The synthesized inulin derivatives were characterized by FT-IR spectra and 1H-NMR. These polycations were tested to evaluate their ability to form non covalent complexes with genetic material (polyplexes). Agarose gel retardation assays showed that the obtained copolymers effectively condensed both plasmid DNA and DNA duplex to form polyplexes at different c/p weight ratios. Moreover, light scattering studies, performed to analyze size and z-potential of polyplexes, evidenced that copolymers are able to interact with genetic material leading to the formation of nanoscale systems. In addiction, biocompatibility of poliplexes was demonstrated by performing citotoxicity assays on a 16HBE cell line. [1] Current Signal Trasduction Therapy, 2010, (5): 92-120 [2] World Patent WO 04002617, January 8, 2004 [3] Aldrichimica Acta, 2004, (37): 66-76.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
