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

Abstract

In this study, two types of biodegradable polycation (PAsp(DET) homopolymer and PEG-PAsp(DET) copolymer) were applied as vectors for inhalable dry gene powders prepared by spray freeze drying (SFD). The prepared dry gene powders had spherical and porous structures with a 5~10-μm diameter, and the integrity of plasmid DNA could be maintained during powder production. Furthermore, it was clarified that PEG-PAsp(DET)-based dry gene powder could more sufficiently maintain both the physicochemical properties and in vitro gene transfection efficiencies of polyplexes reconstituted after powder production than PAsp(DET)-based dry gene powder. From an in vitro inhalation study using an Andersen cascade impactor, it was demonstrated that the addition of l-leucine could markedly improve the inhalation performance of dry powders prepared by SFD. Following pulmonary delivery to mice, both PAsp(DET)- and PEG-PAsp(DET)-based dry gene powders could achieve higher gene transfection efficiencies in the lungs compared with a chitosan-based dry gene powder previously reported by us.

Development of Dry Powder Inhaler Containing Prothionamide-PLGA Nanoparticles Optimized Through Statistical Design: In-vivo Study

“…Rats were divided into two groups: one was treated with DPI of Prothionamide nanoparticles; and the other group was treated with pure Prothionamide [23]. Dry powder inhaler delivery device was designed with little modification as described previously [24]. Tongue was gently pulled outside and sprayed the DPI after placing the DPI device in the trachea region.…”

Comparative Study on Different Drying Methods of Fish Oil Microcapsules

“…It was reported that the microcapsule powders by SFD had a uniform particle size, larger specific surface area, and a better porous character than freeze-dried and spray-dried powders. The powders retained their spherical and porous morphology and could be further coated with an enteric food grade biological polymer and conducive to be absorbed [1,25,26]. Her et al [14] reported that SFD combined the SD and FD processes to obtain fine flavor powder without heat damage, which in turn prevented the drying of the agglomerates, while flavor powder produced by the SFD process typically had a larger surface area and higher fine particle fraction than the particles produced by the SD process, so it could be more quickly and easily rehydrated.…”

Development of New Formulation Dry Powder for Pulmonary Delivery Using Amino Acids to Improve Stability

“…This means that a core-shell type of polyplex micelle was formed, the surface of which was covered with PEG. 31) Interestingly, the powder samples showed an increasing zeta-potential when stored for 12 M or longer (Fig. 7B), suggesting that PEG-PAsp(DET) was decomposed to release the PEG moiety, resulting in the decomposition of the core-shell type of polyplex micelle.…”

“…30) Our previous report indicated that the addition of L-leucine (Leu) to inhalable dry gene powders with PAsp(DET) and PEG-PAsp(DET) led to a decrease in the aggregation and increase in the inhalation properties. 31) However, in-vitro gene transfection efficiencies against CT26 cells of the reconstituted powders containing one of PAsp(DET) and PEGPAsp(DET) were reduced compared to the corresponding sample solutions. Recently, Kataoka and colleagues reported superior in-vitro gene transfection efficiencies of a polyplex with a 1 : 1 mixture of PAsp(DET) and PEG-PAsp(DET).…”