ArticlePharmaceutical research2002
Novel water insoluble lipoparticulates for gene delivery.
Article in Pharmaceutical research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 32 citations in OpenAlex.
- An overview of strategies and challenges adopted to silence BCR-ABL gene by small interfering RNA.Nanomedicine (London, England) · 2025Review
- Exploring the Potential of siRNA Delivery in Acute Myeloid Leukemia for Therapeutic Silencing.Nanomaterials (Basel, Switzerland) · 2023Article
- Polymeric Systems for Cancer Immunotherapy: A Review.Frontiers in immunology · 2022Review
- Radiation-enhanced delivery of plasmid DNA to tumors utilizing a novel PEI polyplex.Cancer gene therapy · 2018Article
- Polymeric oncolytic adenovirus for cancer gene therapy.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe objective was to design and prepare water insoluble lipoparticulates (ISLPs) for efficient gene delivery to lung tissue.
methodsNona[(ethylenimine)-co-[(2-aminoethyl)-N-choleseteryl-oxycarbonyl-ethylenimine]] (NEACE-T) was synthesized in both its free-base and chloride salt-forms using linear polyethylenimine (PEI, Mw 423) as a headgroup and cholesteryl chloroformate as a hydrophobic lipid anchor resulting in a T-shaped lipononamer. Semitelechelic N(alpha)-cholesteryloxycarbonyl nona(ethylenimine) (st-NCNEI-L) was synthesized similarly resulting in a linear lipononamer. As confirmed by 1H-NMR, the site of conjugation was either a primary amine resulting in a linear configuration (st-NCNEI-L) or a secondary amine resulting in a T-shaped configuration (NEACE-T). ISLPs were prepared by combining NEACE-T or st-NCNEI-L with a co-lipid, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) at 1/1, 1/2, and 2/1 molar ratios and the lipoparticulates were hydrated and filtered. ISLP/p2CMVmIL-12 complexes were characterized for particle size, zeta potential, surface morphology, cytotoxicity, and in vitro transfection efficiency.
resultsTransgene expression was dependent on the site of cholesterol conjugation, lipononamer:colipid molar ratio, and ISLP/ p2CMVmIL-12 charge ratios. ISLP/p2CMVmIL-12 complexes were nontoxic to murine colon adenocarcinoma (CT-26) cells at 9/1 (+/-) or lower, had a mean particle size of 330-400 nm while the zeta potential varied from 36-39 mV. Atomic force microscopy (AFM) showed the surface morphology to be that of an oblate spheroid with a size comparable to that determined by dynamic light scattering. ISLP/ p2CMVmIL-12 complexes prepared using free-base NEACE-T:DOPE (1/2) at charge ratios of 3/1 and 5/1 (+/-) provided the highest levels of transgene expression, 18 times more than the levels provided by the salt-form. Secreted levels of mIL-12 p70 were 75 times higher for ISLP/p2CMVmIL-12 complexes than naked p2CMVmIL-12 and nearly 4 times higher than PEI 25 kDa/p2CMVmIL-12 complexes.
conclusionsThe transfection efficiency of the ISLPs was dependent on the site of cholesterol conjugation, amount of colipid, and charge ratio. The highest levels of transgene expression were provided by NEACE-T:DOPE (1/2)/p2CMVmIL-12 at a 3/1 (+/-) charge ratio.
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