Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression

Abstract

Plasmid-loaded microspheres can provide localized and sustained release into the target tissue, and thus have the potential to enhance the efficiency of naked DNA at promoting transgene expression. In this report, microsphere design parameters are investigated by correlating the extent and duration of transgene expression intramuscularly to the polymer molecular weight and the mass of DNA delivered. Plasmid DNA was incorporated into poly (lactide-co-glycolide) microspheres using a cryogenic double emulsion process, and microspheres were injected intramuscularly. Bolus injection of naked plasmid was used for control, which exhibited transfection of muscle cells with transgene expression that gradually decreased over time. Microspheres fabricated from low molecular weight polymer had expression levels that increased from day 1 to day 92, which subsequently decreased through day 174. Decreasing the microsphere mass delivered resulted in steady expression during the same time. However, microspheres fabricated with high molecular weight polymer had expression for only 14 days. Intramuscular injection resulted in a foreign body response to the microspheres, and these infiltrating cells adjacent were primarily transfected. This understanding of microsphere properties that determine transgene expression and the distribution of transfected cells may facilitate their application to fields such as tissue engineering or DNA vaccines.

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

“…Poly (D,Llactide-co-glycolide) (PLGA) is a biodegradable and biocompatible polymer [1]. Encapsulating plasmid DNA (pDNA) in PLGA microspheres protects it from enzymatic degradation and preserves its bioactivity and its ability to exhibit sustained release [2].…”

Development and characterization of pioglitazone loaded liposphere for the effective treatment of diabetes mellitus type 2

“…The aim of the present study was to assess the feasibility of formulating lipospheres of Pioglitazone HCl by melt dispersion technique and obtaining a suitable release pattern. [1][2][3][4][5] cetyl alcohol, gelatin were purchased from S.D. Fine Chemicals Ltd. (India).…”

Influence of particle size and antacid on release and stability of plasmid DNA from uniform PLGA microspheres

“…A major barrier to successful gene therapy is the safe and efficient delivery of DNA to the right place, in the right amount, at the right time. Although many vectors are available for gene therapy, including viruses [1], liposomes [2,3], and polymers [4], biodegradable polymer microparticles have emerged in recent years as a suitable gene delivery vehicle [5][6][7]. Encapsulation and controlled release of plasmid DNA from polymer microspheres provides several advantages.…”

“…Encapsulation and controlled release of plasmid DNA from polymer microspheres provides several advantages. Microparticles allow for access to alternative routes of administration including oral [8], pulmonary [9], subcutaneous [10], and intramuscular [7] pathways.…”

“…Passive targeting of microspheres encapsulating plasmid DNA based on size, via phagocytosis, to professional antigen presenting cells has been demonstrated [10], and active targeting by coating the surface of microspheres with cell-specific ligands is also possible [7,11].…”