PAMAM dendrimers as aerosol drug nanocarriers for pulmonary delivery via nebulization

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Graphical abstractPolyamidoamine (PAMAM) dendrimers were evaluated as nanocarriers for pulmonary delivery of the model poorly soluble anti-asthma drug beclometasone dipropionate (BDP) using G3, G4 and G4(12) dendrimers. BDP-loaded dendrimers were characterized for drug solubility, in vitro drug release and aerosolization properties using three nebulizers: Pari LC Sprint (air-jet), Aeroneb Pro (actively vibrating-mesh) and Omron MicroAir (passively vibrating-mesh) nebulizers. Solubilization of BDP using dendrimers was increased by increasing the dendrimer generation and by using higher pH media. In vitro release studies showed that BDP when complexed with dendrimers exhibited a sustained release, and for all dendrimer formulations less than 35% of the drug was released after 8 h. Nebulization studies revealed that aerosol performance was dependent on nebulizer rather than dendrimer generation. Nebulization output values for the Pari (air-jet) and Aeroneb Pro (active mesh) nebulizers were in the range of 90–92% and 85–89% respectively compared to 57–63% for the Omron (passive mesh) nebulizer. The size of the droplets generated from the jet nebulizer was slightly smaller and aerosol polydispersity was lower compared to both mesh devices. The “fine particle fraction (FPF)” of the aerosols was in the following order: Pari (air-jet) > Aeroneb Pro (active mesh) > Omron (passive mesh). This study demonstrates that BDP-dendrimers have potential for pulmonary inhalation using air-jet and vibrating-mesh nebulizers. Moreover, the aerosol characteristics are influenced by nebulizer design rather than dendrimer generation.

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