Formulations for natural and peptide nucleic acids based on cationic polymeric submicron particles

被引：7

作者：

Cortesi R. ^{[1
]}

Mischiati C. ^{[2
]}

Borgatti M. ^{[2
]}

Breda L. ^{[2
]}

Romanelli A. ^{[3
]}

Saviano M. ^{[3
]}

Pedone C. ^{[3
]}

Gambari R. ^{[2
,4
]}

Nastruzzi C. ^{[5
]}

机构：

[1] Department of Pharmaceutical Sci., University of Ferrara, Ferrara

[2] Dept. of Biochemistry/Molec. Biology, University of Ferrara, Ferrara

[3] Institute of Biostructure/Bioimaging, CNR, Napoli

[4] Lab. Devmt. Pharmacol./Pharmacogen., Biotechnology Centre, University of Ferrara, Ferrara

[5] Dept. of Pharmaceut. Chem./Technol., University of Perugia, Perugia

来源：

AAPS PharmSci | / 6卷 / 1期

关键词：

Delivery; Peptide nucleic acids; Submicron particles;

D O I：

10.1208/ps060102

中图分类号：

学科分类号：

摘要：

This article describes the production and characterization of cationic submicron particles constituted with Eudragit RS 100, plus different cationic surfactants, such as dioctadecyl-dimethyl-ammonium bromide (DDAB18) and diisobutylphenoxyethyl-dimethylbenzyl ammonium chloride (DEBDA), as a transport and delivery system for DNA/DNA and DNA/peptide nucleic acid (PNA) hybrids and PNA-DNA chimeras. Submicron particles could offer advantages over other delivery systems because they maintain unaltered physicochemical properties for long time periods, allowing long-term storage, and are suitable for industrial production. Submicron particles were characterized in terms of size, size distribution, morphology, and zeta potential. Moreover, the in vitro activity and ability of submicron particles to complex different types of nucleic acids were described. Finally, the ability of submicron particles to deliver functional genes to cells cultured in vitro was determined by a luciferase activity assay, demonstrating that submicron particles possess superior transfection efficiency with respect to commercially available, liposome-based transfection kits.

引用

共 17 条

[1] Nielsen P.E., Egholm M., Berg R.H., Buchardt O., Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide, Science, 254, pp. 1497-1500, (1991)
[2] Egholm M., Buchardt O., Nielsen P.E., Berg R.H., Peptide nucleic acids (PNA): Oligonucleotide analogues with an achiral peptide backbone, J. Am. Chem. Soc., 114, pp. 1895-1897, (1992)
[3] Egholm M., Buchardt O., Christiensen L., Et al., PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules, Nature, 365, pp. 566-568, (1993)
[4] Gambari R., Peptide nucleic acids (PNAs): A tool for the development of gene expression modifiers, Curr. Pharm. Design, 7, pp. 1839-1862, (2001)
[5] Demidov V.V., Potaman V.N., Frank-Kamenetsk M.D., Et al., Stability of peptide nucleic acids in human serum and cellular extracts, Biochem. Pharmacol., 48, pp. 1310-1313, (1994)
[6] Scarfi S., Giovine M., Gasparini A., Et al., Modified peptide nucleic acids are internalized in mouse macrophages RAW 264.7 and inhibit inducible nitric oxide synthase, FEBS Lett., 451, pp. 264-268, (1999)
[7] Nastruzzi C., Cortesi R., Esposito E., Et al., Liposomes as carriers for DNA-PNA hybrids, J. Control Release, 68, pp. 237-249, (2000)
[8] Vinayak R., Van der Laan A.C., Brill R., Et al., Automated chemical synthesis of PNA and PNA-DNA chimera on a nucleic acid synthesizer, Nucleosides Nucleotides, 16, pp. 1653-1658, (1997)
[9] van der Laan A.C., Meeuwenoord N.J., Kuyl-Yeheskiely E., Oosting R.S., Brands R., van Boom J.H., Solid support synthesis of a PNA-DNA hybrid, Recl. Trav. Chim. Pays Bas., 114, pp. 295-297, (1995)
[10] Romanelli E., Pedone C., Saviano M., Et al., Molecular interactions between nuclear factor kB (NF-kB) transcription factors and a PNA-DNA chimera mimicking NF-kB binding sites, Eur. J. Biochem., 268, pp. 1-11, (2001)

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