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High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies.
AAPS PharmSciTech. 2014 Dec; 15(6):1574-87.AP

Abstract

Inhalable lung surfactant-based carriers composed of synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), along with paclitaxel (PTX), were designed and optimized as respirable dry powders using organic solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of pulmonary diseases with this current work focusing on lung cancer. In particular, this is the first time dry powder lung surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid-state transitions, amorphous character, residual water content, and phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro aerosol performance using a Next Generation Impactor™ (NGI™) showed measurable powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high-performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 μm with excellent aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions.

Authors+Show Affiliations

Drug Development Division, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25139763

Citation

Meenach, Samantha A., et al. "High-performing Dry Powder Inhalers of Paclitaxel DPPC/DPPG Lung Surfactant-mimic Multifunctional Particles in Lung Cancer: Physicochemical Characterization, in Vitro Aerosol Dispersion, and Cellular Studies." AAPS PharmSciTech, vol. 15, no. 6, 2014, pp. 1574-87.
Meenach SA, Anderson KW, Hilt JZ, et al. High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AAPS PharmSciTech. 2014;15(6):1574-87.
Meenach, S. A., Anderson, K. W., Hilt, J. Z., McGarry, R. C., & Mansour, H. M. (2014). High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AAPS PharmSciTech, 15(6), 1574-87. https://doi.org/10.1208/s12249-014-0182-z
Meenach SA, et al. High-performing Dry Powder Inhalers of Paclitaxel DPPC/DPPG Lung Surfactant-mimic Multifunctional Particles in Lung Cancer: Physicochemical Characterization, in Vitro Aerosol Dispersion, and Cellular Studies. AAPS PharmSciTech. 2014;15(6):1574-87. PubMed PMID: 25139763.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AU - Meenach,Samantha A, AU - Anderson,Kimberly W, AU - Hilt,J Zach, AU - McGarry,Ronald C, AU - Mansour,Heidi M, Y1 - 2014/08/20/ PY - 2014/04/29/received PY - 2014/07/23/accepted PY - 2014/8/21/entrez PY - 2014/8/21/pubmed PY - 2015/7/21/medline SP - 1574 EP - 87 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 15 IS - 6 N2 - Inhalable lung surfactant-based carriers composed of synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG), along with paclitaxel (PTX), were designed and optimized as respirable dry powders using organic solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of pulmonary diseases with this current work focusing on lung cancer. In particular, this is the first time dry powder lung surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid-state transitions, amorphous character, residual water content, and phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro aerosol performance using a Next Generation Impactor™ (NGI™) showed measurable powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high-performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 μm with excellent aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/25139763/High_performing_dry_powder_inhalers_of_paclitaxel_DPPC/DPPG_lung_surfactant_mimic_multifunctional_particles_in_lung_cancer:_physicochemical_characterization_in_vitro_aerosol_dispersion_and_cellular_studies_ L2 - https://dx.doi.org/10.1208/s12249-014-0182-z DB - PRIME DP - Unbound Medicine ER -