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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

  • Research Article
  • Theme: Advances in Formulation and Device Technologies for Pulmonary Drug Delivery
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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.

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Acknowledgments

The authors gratefully acknowledge financial support from the National Institutes of Health (NIH)-National Cancer Institute (NCI) Grant Number R25CA153954 and an NIH-NCI Cancer Nanotechnology Training Center (CNTC) Postdoctoral Traineeship awarded to SAM. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI or the NIH. The authors thank Dr. Tonglei Li for XRPD and HSM access and Dr. J. Zach Hilt for ATR-FTIR access.

Conflict of Interest

No conflicts of interest exist.

Author information

Authors and Affiliations

  1. Drug Development Division, Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA

    Samantha A. Meenach

  2. Department of Chemical and Materials Engineering, College of Engineering, University of Kentucky, Lexington, Kentucky, 40506, USA

    Samantha A. Meenach, Kimberly W. Anderson & J. Zach Hilt

  3. Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky, USA

    Kimberly W. Anderson & J. Zach Hilt

  4. Department of Radiation Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, 40536, USA

    Ronald C. McGarry

  5. Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona, 1703 E. Mabel St, Tucson, Arizona, 85721, USA

    Heidi M. Mansour

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  1. Samantha A. Meenach
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Correspondence to Heidi M. Mansour.

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Guest Editors: Professor Paul B. Myrdal and Dr. Steve W. Stein

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Meenach, S.A., Anderson, K.W., Hilt, J.Z. 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 15, 1574–1587 (2014). https://doi.org/10.1208/s12249-014-0182-z

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