Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 12, Pages 4741-4750Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00532
Keywords
targeted pulmonary delivery; nano-in-microparticles (NIMs); pulmonary chemotherapeutic; aerosolized drug delivery; non-small cell lung cancer; superparamagnetic iron oxide nanoparticles (SPIONs)
Funding
- University of New Mexico, School of Medicine
- Bill and Melinda Gates Grand Challenge Exploration [OPP1061393]
- UNM IDIP [T32-A1007538]
- UNM College of Pharmacy
- Bill and Melinda Gates Foundation [OPP1061393] Funding Source: Bill and Melinda Gates Foundation
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This brief communication evaluates the cytotoxicity and targeting capability of a dry powder chemotherapeutic. Nano-in-microparticles (NIMs) are a dry powder drug delivery vehicle containing superparamagnetic iron oxide nanoparticles (SPIONs) and either doxorubicin (w/w solids) or fluorescent nanospheres (w/v during formulation; as a drug surrogate) in a lactose matrix. In vitro cytotoxicity was evaluated in A549 adenocarcinoma cells using MTS and LDH assays to assess viability and toxicity after 48 h of NIMs exposure. In vivo magnetic-field-dependent targeting of inhaled NIMs was evaluated in a healthy mouse model. Mice were endotracheally administered fluorescently labeled NIMs either as a dry powder or a liquid aerosol in the presence of an external magnet placed over the left lung. Quantification of fluorescence and iron showed a significant increase in both fluorescence intensity and iron content to the left magnetized lung. In comparison, we observed decreased targeting of fluorescent nanospheres to the left lung from an aerosolized liquid suspension, due to the dissociation of SPIONs and nanoparticles during pulmonary administration. We conclude that dry powder NIMs maintain the therapeutic cytotoxicity of doxorubicin and can be better targeted to specific regions of the lung in the presence of a magnetic field, compared to a liquid suspension.
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