期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 5, 期 12, 页码 6570-6580出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.9b00947
关键词
Paclitaxel nanocomposite microparticles; lung cancer; pulmonary delivery; multicellular tumor spheroids; air-interface cell culture
资金
- Institutional Development Award (IDeA) Network for Biomedical Research Excellence from the National Institute of General Medical Sciences of the National Institutes of Health [P20GM103430]
- National Science Foundation EPSCoR [EPS-1004057]
- National Science Foundation [1508868]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1508868] Funding Source: National Science Foundation
Paclitaxel (as intravenous Taxol) is one of the most applied chemotherapeutics used for the treatment of lung cancer. This project involves the development of a dry powder nanocomposite microparticle (nCmP) aerosol containing PTX-loaded nanoparticles (NP) to be delivered via a dry powder inhaler to the lungs for the treatment of non-small cell lung cancer (NSCLC). Nanoparticles were formulated by a single emulsion and solvent evaporation method, producing smooth, neutral PTX NP of approximately 200 nm in size. PTX nCmP were obtained via spray drying PTX NP with mannitol, producing amorphous wrinkled particles that demonstrated optimal aerosol deposition for in vitro pulmonary delivery. Free PTX, PTX NP, and PTX nCmP were evaluated in vitro in both 2D monolayers and 3D multicellular spheroids (MCS). PTX NP enhanced cytotoxicity when compared to pure drug in the 2D evaluation. However, on a liquid culture 3D tumor spheroid model, PTX NP and pure PTX showed similar efficacy in growth inhibition of MCS. The PTX nCmP formulation had a comparable cytotoxicity impact on MCS compared with free PTX. Finally, PTX nCmP were evaluated in an air-grown 3D MCS platform that mimics the pulmonary environment, representing a new model for the assessment of dry powder formulations.
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