Comparative assessment of plasmid DNA delivery by encapsulation within or adsorbed on poly (D, L-lactide-coglycolide) nanoparticles

Abd Almonem Doolaanea,Mohd Affendi Bin Mohd Shafri,Nurul Hafizah Mohd Nor,Farahidah Mohamed,Nur Izzati Mansor

doi:10.4314/tjpr.v17i1.1

Abstract

Purpose : To compare the gene delivery effectiveness of plasmid DNA (pDNA) encapsulated within poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles with that adsorbed on PLGA nanoparticles. Methods: PLGA nanoparticles were prepared using solvent-evaporation method. To encapsulate pDNA within the particles, it was first complexed with cetyltrimethylammonium bromide (CTAB) and then added to the oil phase during the synthesis. For the adsorption, PLGA nanoparticles were first modified with either CTAB or chitosan and then pDNA was adsorbed on the particle surface by electrostatic interaction. Results : Nanoparticles encapsulating pDNA exhibited better plasmid loading and protection with significantly lower burst release (p < 0.05) compared to that of the nanoparticles with adsorbed plasmid. Cell uptake of chitosan-modified nanoparticles by murine neuroblastoma (N2a) cells was significantly (p < 0.05) higher than that of chitosan-free nanoparticles. Nanoparticles encapsulating pDNA showed higher transfection efficiency (p < 0.05) in N2a cells. Conclusion : Encapsulation of pDNA within PLGA nanoparticles presents a potential strategy for gene delivery that is superior to pDNA adsorbed on the nanoparticle surface. In addition, encapsulation keeps the particle surface free for further modifications such as the addition of targeting ligands. Keywords : Poly (D,L-lactide-co-glycolide), Plasmid DNA, Encapsulation, Adsorption, Cellular uptake, Gene therapy, Targeting ligands

Highlights

Gene therapy has shown promising results in the treatment of a wide range of diseases
F1 complexed with plasmid DNA (pDNA) underwent significant increase in both particle size and polydispersity
F1, F3 and F4 revealed similar particle size when complexed with pDNA (p > 0.05)

Summary

Introduction

Gene therapy has shown promising results in the treatment of a wide range of diseases. Microparticles and PLGA nanoparticles have been frequently used to deliver nucleic acids after being modified to bear positive charges. The positively-charged particles interact with the negatively-charged nucleic acids by means of electrostatic interactions. Some of the commonly used surface modifying materials are chitosan [3], cetyltrimethylammonium bromide (CTAB) [4] and poly-L-lysine (PLL) [5]. Another approach for delivering nucleic acids is by encapsulating them within PLGA microparticles or nanoparticles [6]. Every approach for encapsulation of PDNA may have its own advantages and disadvantages

Results

Discussion

Conclusion