title: Development of polymeric-cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery.
abstract: We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid-polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK ; Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Jain
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Massey
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Helmy
authors.initials: H
authors.lastname: Yusuf
authors.affiliation: Centre for Vision & Vascular Science, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Denise M
authors.initials: DM
authors.lastname: McDonald
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
authors.affiliation: School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Vicky L
authors.initials: VL
authors.lastname: Kett
mesh_terms: D002412:Cations; D045744:Cell Line, Tumor; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013696:Temperature; D014162:Transfection
chemical_list: D002412:Cations; D057846:Cell-Penetrating Peptides; D010455:Peptides; C000596539:RALA peptide; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D004247:DNA
keywords: DNA; PLA-PEG; cationic peptide; composite nanoparticles; gene delivery; transfection