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LARGE SIZE DNA IN VITRO AND IN VIVO DELIVERY USING CHITOSAN TRANSFECTION

100%

Sankov V., Shagdarova B., Varlamov V., Esipov R., Svirshchevskaya E.

Progress on Chemistry and Application of Chitin and its Derivatives

2017

vol. 22

190 - 200

In modern medicine, many diseases can be treated using gene therapy, which requires a DNA delivery system to prevent DNA from degradation and to transport it to the cells. Liposomal reagents are expensive for such a therapy and new inexpensive biodegradable DNA carriers are required. Chitosan (Ch) is a cationic polymer with promising potency for gene delivery. Some Ch derivatives have been shown to efficiently transfect mammalian cells in vitro. However, there are many inconsistencies in the literature concerning the effectiveness of Ch systems for in vivo gene transfer. The aim of this work was to develop a Ch-based vector for in vivo delivery of a large-size DNA fragment coding for the far-red fluorescent protein (RFP). Among several Ch derivatives, hexanoyl-Ch (HCh) with a molecular weight of 20 kDa effectively transfected cells in vitro. Intratumoural injection of polyplexes in colon and lung tumours resulted in local expression of RFP in tumours.

DEVELOPMENT OF MUCOADHESIVE CHITOSAN-BASED DRUG DELIVERY SYSTEM

86%

Konovalova M., Shagdarova B., Zubareva A., Generalov A., Grechikhina M., Svirshchevskaya E.

Chitosan is a highly versatile biopolymer characterised by low toxicity, biocompatibility, and slow but complete biodegradation in the human body, possessing multiple reactive groups. One of the most well-known properties of positively charged chitosan derivatives is their ability to bind mucous membranes. The aim of this work was the analysis of mucoadhesion of unmodified 20 kDa chitosan and its hydrophobic (HC) and hydrophobic quaternised (QHC) derivatives in vitro and ex vivo. Unmodified chitosan formed large aggregates in vitro in keratinocyte and colon cell cultures and ex vivo in murine small intestine and muscle explants. At the same time, HC and especially QHC bound cells in vitro and ex vivo in a fine dotted manner, as evidenced by confocal microscopy. Such a pattern of hydrophobic derivatives distribution provides the possibility to develop mucoadhesive drug delivery systems with increased local drug release and improved chitosan biodegradation.

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2 Progress on Chemistry and Application of Chitin and its Derivatives

1 2018

1 2017

2 Shagdarova B.

2 Svirshchevskaya E.

1 Esipov R.

1 Generalov A.

1 Grechikhina M.

1 Konovalova M.

1 Sankov V.

1 Varlamov V.

1 Zubareva A.

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LARGE SIZE DNA IN VITRO AND IN VIVO DELIVERY USING CHITOSAN TRANSFECTION

DEVELOPMENT OF MUCOADHESIVE CHITOSAN-BASED DRUG DELIVERY SYSTEM