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Development of polymeric–cationic peptide composite nanoparticles, a nanoparticle-in-nanoparticle system for controlled gene delivery

Authors Jain AK, Massey A, Yusuf H, McDonald DM, McCarthy HO, Kett VL

Received 27 August 2015

Accepted for publication 7 October 2015

Published 24 November 2015 Volume 2015:10(1) Pages 7183—7196

DOI https://doi.org/10.2147/IJN.S95245

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lakshmi Kiran Chelluri

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Arvind K Jain,1,2 Ashley Massey,1 Helmy Yusuf,1 Denise M McDonald,3 Helen O McCarthy,1 Vicky L Kett1

1School of Pharmacy, Medical Biology Centre, Queen’s University Belfast, Belfast, Northern Ireland, UK, 2Weatherall Institute of Molecular Medicine, MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Oxford, UK, 3Centre for Vision & Vascular Science, Queen’s University Belfast, Belfast, Northern Ireland, UK

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.

Keywords: PLA-PEG, cationic peptide, gene delivery, composite nanoparticles, DNA, transfection

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