Thermosensitive Polysaccharide Particles for Pulmonary Drug Delivery
2019
Abstract In the present study, we have prepared drug carriers for pulmonary administration: temperature-responsive polysaccharide particles prepared through an emulsion formation and a subsequent sol-gel transition of polysaccharides. The particles are obtained by the cooling of w/o (water-in-oil) emulsions prepared from an aqueous polysaccharide solution and a surfactant-dissolving organic solvent. We found that highly stable s/o (solid-in-oil) suspensions were formed regardless of HLB value, structure, and composition of the surfactants when high-molecular-weight surfactants were used. There are two possible important factors affecting the formation of spherical κ-carrageenan particles: (1) the formation of physically crosslinked domains inside the particle by means of the increase of concentrations of polysaccharides and cations and (2) the formation of a stable solid-liquid interfaces by using high-molecular-weight surfactants. We obtained stable polysaccharide particles with dimpled surfaces. As a result of the in vitro aerosol dispersion performance of the κ-carrageenan particles with the cascade impactor, we identified the characteristic delivery behavior of κ-carrageenan particles: the κ-carrageenan particles delivered more to the alveoli than to the pharynx and bronchi, despite their high density. The present study shows that the “dimpled” κ-carrageenan particles can likely stay in the alveoli so that high therapeutic effects will likely occur in pulmonary administration.
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