Comparison of post-emulsification freeze drying or spray drying processes for the microencapsulation of plasmid DNA

Abstract

In this work, methods used to microencapsulate plasmid DNA in a biodegradable polymer were compared for their effects on the physicochemical characteristics of DNA-loaded microparticles and on the release and integrity of encapsulated DNA. Microparticles were formulated by either w/o/w emulsification and freeze-drying (EFD) or by w/o/w emulsification and spray-drying (ESD). The influence of both manufacturing processes on particle morphology, charge, release characteristics and biological activity of encapsulated DNA was evaluated. Particles produced by emulsification/spray-drying exhibited more diversity in shape and size than those produced by emulsification/freeze-drying. These particles also exhibited higher plasmid DNA encapsulation efficiency than particles produced by emulsification/freeze-drying. The fractional DNA release rates were similar over the first 25 days for both formulations, release rate declining more rapidly at later times for the ESD product. Mammalian cell transfection assays confirmed the biological activity of encapsulated DNA extracted from both types of particles, with significantly higher transfection levels being observed for ESD particles. Application of a double emulsion (w/o/w) before spray drying resulted in higher encapsulation levels (> 90%) relative to previous literature values, which used single (w/o) emulsions before spray drying. The emulsification/spray-drying technique described here appears to be a rapid and efficient method for the preparation of PLGA microparticles loaded with plasmid DNA.

Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers

“…Therefore, some researchers have explored the use of spray-drying as an alternative method to freeze-drying [2,17,[44][45][46].…”

“…[26, 35,101] and PLGA [44,74,82,98,[102][103][104][105][106], or hydrophilic ones such as chitosan [25,45,56,94,[107][108][109][110][111], alginate [37,112], poly(vinylpyrrolidone) (PVP) [113,114], hydroxypropylmethylcellulose (HPMC) [69] and gelatin [50,115] are initially dissolved in organic or aqueous solvents, respectively, and then spray-dried. In the former, the main advantage is the use of solvents with low boiling point.…”

Formulating Poly(Lactide-Co-Glycolide) Particles for Plasmid DNA Delivery

“…Cell transfection assays have confirmed the biological activity of encapsulated DNA is significantly higher for spray dried particles. 58 While these methodologies have generated significant improvements in pDNA entrapment in PLGA particles, optimization of several other formulation parameters can also significantly affect pDNA entrapment and functional release.…”

Development of Biodegradable Polycation-Based Inhalable Dry Gene Powders by Spray Freeze Drying

“…Although reports on the development of DPIs for pulmonary gene therapy are still limited, some powder production techniques, including spray drying (SD), supercritical fluid precipitation, and lyophilization, might be applicable for a specific formulation or condition [ 9 , 10 , 11 ]. However, the destabilization of the gene or delivery system caused by several stresses, including heating, freezing, spraying, and shear force, must be considered during powder production [ 9 , 12 , 13 , 14 , 15 ]. Moreover, the morphology and particle size of prepared powders are critical factors affecting their inhalability.…”