Cationic stearylamine-containing biodegradable microparticles for DNA delivery

Abstract

Technical aspects for preparing a new type of cationic stearylamine (SA)-containing microparticle as a potential drug delivery system for negatively charged therapeutics were investigated. Cationic biodegradable microparticles based on poly(lactide) and poly(lactide-co-glycolide) were prepared upon incorporation of SA either by solvent evaporation or by spray-drying. Water-insoluble SA offers the advantage over other water-soluble cationic compounds that it can be dissolved directly in the organic solution together with the polymers. This facilitated the subsequent preparation of the microparticle formulations. Particle size was controlled by the respective process parameters, resulting in either large polymer aggregates within the range 50-100 micro m or small spherical microparticles within the range 1-10 micro m. The incorporation of SA into the formulations also improved particle characteristics in terms of re-dispersibility, reduced sticking, and particle size uniformity. Both circular plasmid DNA (5 kbp) and linear salmon DNA (0.5 kbp) were efficiently adsorbed to the cationic SA microparticle surfaces. Preliminary tests on the release of DNA from spray-dried SA microparticles showed an immediate burst release, which was followed by a delayed second release phase for more than 4 weeks. The cationic SA microparticles might provide a potential drug-delivery system to improve the efficacy for protein and DNA-type therapeutics.

Inhalable large porous microspheres of low molecular weight heparin: In vitro and in vivo evaluation

“…However, no significant differences were observed between the morphologies of the Span 60-and stearylamine-modified particles despite the two surfactants being electrostatically different. Uniform sized particles with rough surfaces have previously been observed when neutral or cationic surfactants were incorporated in the internal aqueous or OP of the primary emulsion [10,11,30]. The rough surface of the particles was caused by shrinkage of the polymer as water was being removed during drying.…”

Pharmaceutical Particle Engineering via Spray Drying

“…Developments in the area of bioactive surface layers seem particularly promising. For example, the surface of spray dried microparticles has been loaded with covalently bonded antibodies ( 402 ) or adsorbed DNA ( 403 , 404 ) for immunomodulation purposes.…”

Non-Viral Delivery Systems in Gene Therapy

“…To enhance the DNA loading, several strategies have been proposed. Kusonowiriyawong et al [31] prepared cationic PLGA microparticles by dissolving cationic surfactants (like water insoluble stearylamine) in the organic solvent in which the PLGA was dissolved to prepare the microparticles. Another strategy was to reduce the negative charge of plasmid DNA by condensing it with poly(aminoacids) (like poly-L-lysine) before encapsulation in PLGA microparticles [32,33].…”