Chitosan Oleate Coated PLGA Nanoparticles as siRNA Drug Delivery System

Pharmaceutics

Maria Cristina Bonferoni¹  Silvia Rossi¹  Laura Catenacci¹  Dalila Miele¹  Franca Ferrari¹  Milena Sorrenti¹  Giuseppina Sandri¹  John J. Rossi²  Xin Xia² 

[1] Department Drug Sciences, University of Pavia, Vle Taramelli 12, 27100 Pavia, Italy;Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, 1218 Fifth Avenue, Duarte, CA 91010, USA;

关键词: nucleic acid delivery;    PLGA nanoparticles;    chitosan oleate;    siRNA;    polyplexes;   

DOI  :  10.3390/pharmaceutics13101716

来源: DOAJ

【 摘 要 】

Oligonucleotide therapeutics such as miRNAs and siRNAs represent a class of molecules developed to modulate gene expression by interfering with ribonucleic acids (RNAs) and protein synthesis. These molecules are characterized by strong instability and easy degradation due to nuclease enzymes. To avoid these drawbacks and ensure efficient delivery to target cells, viral and non-viral vectors are the two main approaches currently employed. Viral vectors are one of the major vehicles in gene therapy; however, the potent immunogenicity and the insertional mutagenesis is a potential issue for the patient. Non-viral vectors, such as polymeric nanocarriers, provide a safer and more efficient delivery of RNA-interfering molecules. The aim of this work is to employ PLGA core nanoparticles shell-coated with chitosan oleate as siRNA carriers. An siRNA targeted on HIV-1, directed against the viral Tat/Rev transcripts was employed as a model. The ionic interaction between the oligonucleotide’s moieties, negatively charged, and the positive surface charges of the chitosan shell was exploited to associate siRNA and nanoparticles. Non-covalent bonds can protect siRNA from nuclease degradation and guarantee a good cell internalization and a fast release of the siRNA into the cytosolic portion, allowing its easy activation.

【 授权许可】

Unknown