Microparticle‐mediated gene delivery for the enhanced expression of a 19‐kDa fragment of merozoite surface protein 1 of Plasmodium falciparum

Abstract

The 19 kDa carboxyl-terminal fragment of merozoite surface protein 1 (MSP1(19)) is a major component of the invasion-inhibitory response in individual immunity to malaria. A novel ultrasonic atomization approach for the formulation of biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles of malaria DNA vaccines encoding MSP1(19) is presented here. After condensing the plasmid DNA (pDNA) molecules with a cationic polymer polyethylenimine (PEI), a 40 kHz ultrasonic atomization frequency was used to formulate PLGA microparticles at a flow rate of 18 mL h(-1). High levels of gene expression and moderate cytotoxicity in COS-7 cells were achieved with the condensed pDNA at a nitrogen to phosphate (N/P) ratio of 20, thus demonstrating enhanced cellular uptake and expression of the transgene. The ability of the microparticles to convey pDNA was examined by characterizing the formulated microparticles. The microparticles displayed Z-average hydrodynamic diameters of 1.50-2.10 microm and zeta potentials of 17.8-23.2 mV. The encapsulation efficiencies were between 78 and 83%, and 76 and 85% of the embedded malaria pDNA molecules were released under physiological conditions in vitro. These results indicate that PLGA-mediated microparticles can be employed as potential gene delivery systems to antigen-presenting cells in the prevention of malaria.

Extracellular vesicles in malaria: an agglomeration of two decades of research

“…A number of earlier malaria vaccine studies focused on developing synthetic nanoparticles and microparticles for the delivery of parasite genes or proteins and a majority of the formulations included the biocompatible polymer poly (lactic-co-glycolic acid)—PLGA [ 129 – 134 ]. For the first time, iREVs from in vitro P. falciparum cultures and corresponding uninfected RBC derived EVs (uREVs), have been evaluated for their potential as natural antimalarial drug delivery systems [ 118 ].…”

Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery

“…The same group subsequently reported high levels of gene expression and moderate cytotoxicity in COS-7 cells using a similar carrier with plasmid DNA encoding PyMSP1-19 formulated via ultrasonic atomization. 5 Previously, we have shown that magnetofection significantly improved the transfection efficiency of DNA encoding P. yoelii merozoite surface protein1-19 (MSP1-19) (VR1020-PyMSP1- 19) in COS-7 cells. 6 The vector compositions of superparamagnetic iron oxide nanoparticles (SPIONs) and PEI complexed under acidic condition showed better DNA transfection than at neutral condition, possibly due to the protonated structures of PEI polymer that entrapped and condensed higher amounts of DNA.…”

Role of Extracellular Vesicles in Cellular Cross Talk in Malaria

“…The delivery of P. vivax antigens using PLGA as a vehicle demonstrated promising and improved immune response when compared to standard vaccination technique (128). In addition, PLGA microparticles have been used to deliver Plasmodium antigenencoding plasmid DNA to antigen-presenting cells (129). Targeting the sexual stage of the parasite by transmission blocking vaccines have been shown to be promising but less efficient.…”