- Title
- Engineering pH-sensitive dissolution of lipid-polymer nanoparticles by Eudragit integration impacts plasmid DNA (pDNA) transfection
- Creator
- Santhanes, Diviya; Zhang, Huiming; Wilkins, Alex; John Aitken, Robert; Gannon, Anne-Louise; Liang, Mingtao
- Relation
- European Journal of Pharmaceutics and Biopharmaceutics Vol. 199, Issue June 2024, no. 114299
- Publisher Link
- http://dx.doi.org/10.1016/j.ejpb.2024.114299
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2024
- Description
- Lipid-polymer nanoparticles offer a promising strategy for improving gene nanomedicines by combining the benefits of biocompatibility and stability associated with the individual systems. However, research to date has focused on poly-lactic-co-glycolic acid (PLGA) and resulted in inefficient transfection. In this study, biocompatible Eudragit constructs E100 and RS100 were formulated as lipid-polymer nanoparticles loaded with pDNA expressing red fluorescent protein (RFP) as a model therapeutic. Using a facile nanoprecipitation technique, a core-shell structure stabilised by lipid-polyethylene glycol (PEG) surfactant was produced and displayed resistance to ultracentrifugation. Both cationic polymers E100 (pH-sensitive dissolution at 5) and RS100 (pH-insensitive dissolution) produced 150-200 nm sized particles with a small positive surface charge (+3-5 mV) and high pDNA encapsulation efficiencies (EE) of 75-90 %. The dissolution properties of the Eudragit polymers significantly impacted the biological performance in human embryonic kidney cells (HEK293T). Nanoparticles composed of polymer RS100 resulted in consistently high cell viability (80-100 %), whereas polymer E100 demonstrated dose-dependent behaviour (20-90 % cell viability). The low dissolution of polymer RS100 over the full pH range and the resulting nanoparticles failed to induce RFP expression in HEK293T cells. In contrast, polymer E100-constructed nanoparticles resulted in reproducible and gradually increasing RFP expression of 26-42 % at 48-72 h. Intraperitoneal (IP) injection of the polymer E100-based nanoparticles in C57BL/6 mice resulted in targeted RFP expression in mouse testes with favourable biocompatibility one-week post-administration. These findings predicate Eudragit based lipid-polymer nanoparticles as a novel and effective carrier for nucleic acids, which could facilitate pre-clinical evaluation and translation of gene nanomedicines.
- Subject
- plasmid DNA (pDNA); eudragit lipid-polymer; lipid-polymer nanoparticles; nanoprecipitation; gene transfection
- Identifier
- http://hdl.handle.net/1959.13/1502883
- Identifier
- uon:55286
- Identifier
- ISSN:0939-6411
- Language
- eng
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