Abstract
Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene delivery systems to increase stability as well as decrease toxicity and nonspecific interactions, thereby increasing transfection efficiency. In this work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery systems. For this purpose, we describe the design and evaluation of these nanosystems loaded with plasmid DNA, including an evaluation of their physicochemical characteristics, stability properties, ability to protect and efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid (pEGFP) in vitro, and biocompatibility both in vitro and in vivo. We confirm that molecules with high biological value and targeting potential, such as HA and CS, can be successfully incorporated into our recently developed sorbitan ester-based nanoparticles (SENS) and that this incorporation leads to effective stabilisation of both nanosystems as well as protects plasmid DNA. We demonstrated that the aforementioned incorporation of HA and CS enables long-term stability of the nanosystems in both liquid and lyophilised states, which is a remarkable property that can aid in their transfer to industry. The ability of these functionalised nanosystems to transfect the A549 cell line without compromising cell viability was also shown, as well as their innocuous safety profile in vivo. Thus, we provide valuable evidence of the suitable properties and potential of these hybrid nanoparticles as gene delivery systems.
Original language | English |
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Pages (from-to) | 85-94 |
Number of pages | 10 |
Journal | European Journal of Pharmaceutics and Biopharmaceutics |
Volume | 125 |
Early online date | 19 Jan 2018 |
DOIs | |
Publication status | Published - 1 Apr 2018 |
Funding
This work was supported by grants from the Ministry of Economy and Competitiveness of Spain (MAT2013-47501-C2-2-R) and Xunta de Galicia (Competitive Reference Groups, FEDER Funds, Ref. 2014/043). I. Fernandez-Piñeiro acknowledges the Spanish Ministry of Education, Culture and Sports for the FPU scholarship FPU13/00342.
Keywords
- Chondroitin sulfate
- DNA
- Gene delivery
- Hyaluronic acid
- Lipid nanoparticles
- Natural polymers
ASJC Scopus subject areas
- Biotechnology
- Pharmaceutical Science