Biodegradable Nanoparticle Flocculates for Dry Powder Aerosol Formulation

Abstract

Uncontrolled agglomeration presents a formidable encumbrance to nanoparticle formulation as a dry powder for inhalation therapy. Spray-drying and freeze-drying of nanosuspensions has demonstrated some success in creating dry powders composed of agglomerated nanoparticles with appropriate aerodynamic properties. These controlled drying processes, however, may require an undesirable amount of excipient to maintain an active therapeutic while generating dry powders and may not offer the desired control over agglomerate size and aerosolizability. As a potential alternative approach, a method for flocculating nanoparticles in solution followed by freeze-drying is reported. Biodegradable poly(DL-lactic-co-glycolic acid) nanoparticles were self-assembled into flocs via electrostatic interactions between nanoparticles coated with oppositely charged polyelectrolytes. The size of the nanoparticle flocs was readily controlled by manipulating the mixing ratio of charged nanoparticles. Freeze-drying the flocculated nanoparticles produced dry powders exhibiting low density (approximately 0.1 g/cm3), a weblike morphology, and desirable aerodynamic properties suited for dry powder aerosols.

Nanosized rods agglomerates as a new approach for formulation of a dry powder inhaler

“…For a gglomeration, the addition of monovalent cations is a well known procedure resulting in the agglomeration of phospholipids, solid lipid nanoparticles, and nanosuspensions. 42,51,52 It was reported that different types of monovalent cations can be chosen in order to control the degree of agglomeration. 53 The order of the capability of monovalent cations to induce the initial phase of the agglomeration of large phospholipid vesicles was reported to be: Li + .…”

Nanoparticle agglomerates of fluticasone propionate in combination with albuterol sulfate as dry powder aerosols

“…Inhaled drugs should ideally possess an aerodynamic diameter less than 5 µm for delivery into the ‘deep’ lung for local therapy or systemic absorption (Weers et al, 2010). Nanoparticles (<0.5 µm) are more likely to be exhaled, which may lead to dose variability (Shi et al, 2007). If delivered as a suspension, such small particles are also prone to particle growth due to Ostwald ripening and can suffer from uncontrolled agglomeration (Berkland, 2010).…”

Combination Chemotherapeutic Dry Powder Aerosols via Controlled Nanoparticle Agglomeration

“…1). This may be due to the deposition of nanoparticles on agglomerates during lyophilization or to cohesion between agglomerates as a result of drying (57). Furthermore, it was clear that the combination lyophilized powders had a broader distribution compared to the other two formulations (F1 and F2).…”