Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects.

Despite immense revolutionary therapeutics potential, sustaining release of active small interfering RNA (siRNA) remains an arduous challenge. The development of nanoparticles with siRNA sustained release capabilities provides an avenue to enhance the therapeutic efficacy of gene-based therapy. Herein, we present a new system based on the encapsulation of siRNA/chitosan-methacrylate (CMA) complexes into liposomes to form UV crosslinkable Nanolipogels (NLGs) with sustained siRNA-release properties in vitro. We demonstrated that the CMA nanogel in NLGs can enhance the encapsulation efficiency of siRNA and provide sustained release of siRNA up to 28 days. To understand the particle mechanism of cellular entry, multiple endocytic inhibitors have been used to investigate its endocytosis pathways. The study saw positively charged NLGs entering cells via multiple endocytosis pathways, facilitating endosomal escape and slowly releasing siRNA into the cytoplasm. Transfection experiments confirmed that the crosslinked NLG delivery system provides effective transfection and prolonged silencing effect up to 14 days in cell cultures. We expect that this sustained-release siRNA NLG platform would be of interest in both fundamental biological studies and in clinical applications to extend the use of siRNA-based therapies.

Recent Advances in Chitosan-Based Carriers for Gene Delivery.

Approximately 4000 diseases are associated with malfunctioning genes in a particular cell type. Gene-based therapy provides a platform to modify the disease-causing genes expression at the cellular level to treat pathological conditions. However, gene delivery is challenging as these therapeutic genes need to overcome several physiological and intracellular barriers in order, to reach the target cells. Over the years, efforts have been dedicated to develop efficient gene delivery vectors to overcome these systemic barriers. Chitosan, a versatile polysaccharide, is an attractive non-viral vector material for gene delivery mainly due to its cationic nature, biodegradability and biocompatibility. The present review discusses the design factors that are critical for efficient gene delivery/transfection and highlights the recent progress of gene therapy using chitosan-based carriers.