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Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery.
Pulm Pharmacol Ther. 2020 10; 64:101975.PP

Abstract

The purpose of this study was to design, develop and characterize inhalable proliposomal microparticles/nanoparticles of Amphotericin B (AmB) with synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) which are lung surfactant-mimic phospholipids. Organic solutions of AmB and phospholipids, were co-spray dried using an advanced closed-mode system and a high performance cyclone. Scanning electron microscopy (SEM) was employed to visualize the surface structure, morphology, and particles size. The residual water content of the proliposomes was quantified by Karl Fisher coulometric titration (KFT). Degree of crystallinity/non-crystallinity was measured by X-ray powder diffraction (XRPD). Phase behavior was measured by differential scanning calorimetry. The chemical composition by molecular fingerprinting was established using attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy. The amount of AmB loaded into the proliposomes was quantified using UV-VIS spectroscopy. The in vitro aerosol dispersion performance was conducted using the Next Generation Impactor (NGI) and the human dry powder inhaler (DPI) (Handihaler®) that is FDA-approved. Different human lung cell lines were employed to demonstrate in vitro safety as a function of dose and formulation. Smooth, spherical microparticles/nanoparticles were formed at medium and high spray drying pump rates and had low residual water content. A characteristic peak in the XRPD diffraction pattern as well as an endotherm in DSC confirmed the presence of the lipid bilayer structure characteristic in the DPPC/DPPG proliposomal systems. Superior in vitro aerosol performance was achieved with engineered microparticles/nanoparticles demonstrating suitability for targeted pulmonary drug delivery as inhalable dry powders. The in vitro cellular studies demonstrated that the formulated proliposomes are safe. These AmB proliposomes can be a better option for targeted treatment of severe pulmonary fungal infections.

Authors+Show Affiliations

The University of Arizona College of Pharmacy, Dept of Pharmaceutical Sciences, Tucson, AZ, USA; The University of Arizona College of Engineering, Department of Biomedical Engineering, Tucson, AZ, USA; The University of Arizona College of Medicine, Department of Medicine, Division of Translational & Regenerative Medicine, Tucson, AZ, USA.The University of Arizona College of Pharmacy, Dept of Pharmaceutical Sciences, Tucson, AZ, USA.The University of Arizona College of Pharmacy, Dept of Pharmaceutical Sciences, Tucson, AZ, USA.The University of Arizona College of Medicine, Department of Medicine, Division of Translational & Regenerative Medicine, Tucson, AZ, USA.The University of Arizona College of Medicine, Department of Medicine, Division of Translational & Regenerative Medicine, Tucson, AZ, USA; The University of Arizona College of Medicine, Department of Medicine, Center for Lung Vascular Pathobiology, Tucson, AZ, USA; The University of Arizona College of Medicine, Department of Physiology, Tucson, AZ, USA.The Ohio State University College of Medicine, Department of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Columbus, AZ, USA; The Ohio State University College of Medicine, The Davis Heart and Lung Research Institute, Columbus, OH, USA.The University of Arizona College of Pharmacy, Dept of Pharmaceutical Sciences, Tucson, AZ, USA; The University of Arizona College of Medicine, Department of Medicine, Division of Translational & Regenerative Medicine, Tucson, AZ, USA; The University of Arizona, Institute of the Environment, Tucson, AZ, USA; The University of Arizona, BIO5 Research Institute, Tucson, AZ, USA; The University of Arizona, National Cancer Institute Comprehensive Cancer Center, Tucson, AZ, USA. Electronic address: mansour@pharmacy.arizona.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

33137515

Citation

Gomez, Alexan I., et al. "Advanced Spray Dried Proliposomes of Amphotericin B Lung Surfactant-mimic Phospholipid Microparticles/nanoparticles as Dry Powder Inhalers for Targeted Pulmonary Drug Delivery." Pulmonary Pharmacology & Therapeutics, vol. 64, 2020, p. 101975.
Gomez AI, Acosta MF, Muralidharan P, et al. Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery. Pulm Pharmacol Ther. 2020;64:101975.
Gomez, A. I., Acosta, M. F., Muralidharan, P., Yuan, J. X., Black, S. M., Hayes, D., & Mansour, H. M. (2020). Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery. Pulmonary Pharmacology & Therapeutics, 64, 101975. https://doi.org/10.1016/j.pupt.2020.101975
Gomez AI, et al. Advanced Spray Dried Proliposomes of Amphotericin B Lung Surfactant-mimic Phospholipid Microparticles/nanoparticles as Dry Powder Inhalers for Targeted Pulmonary Drug Delivery. Pulm Pharmacol Ther. 2020;64:101975. PubMed PMID: 33137515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery. AU - Gomez,Alexan I, AU - Acosta,Maria F, AU - Muralidharan,Priya, AU - Yuan,Jason X-J, AU - Black,Stephen M, AU - Hayes,Don,Jr AU - Mansour,Heidi M, Y1 - 2020/10/31/ PY - 2020/08/07/received PY - 2020/10/07/revised PY - 2020/10/26/accepted PY - 2020/11/3/pubmed PY - 2021/9/18/medline PY - 2020/11/2/entrez KW - Co-spray drying particle engineering KW - Human inhaler device KW - In vitro aerosol dispersion KW - In vitro human pulmonary cell viability KW - Lung surfactant phospholipids KW - Pulmonary drug delivery SP - 101975 EP - 101975 JF - Pulmonary pharmacology & therapeutics JO - Pulm Pharmacol Ther VL - 64 N2 - The purpose of this study was to design, develop and characterize inhalable proliposomal microparticles/nanoparticles of Amphotericin B (AmB) with synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) which are lung surfactant-mimic phospholipids. Organic solutions of AmB and phospholipids, were co-spray dried using an advanced closed-mode system and a high performance cyclone. Scanning electron microscopy (SEM) was employed to visualize the surface structure, morphology, and particles size. The residual water content of the proliposomes was quantified by Karl Fisher coulometric titration (KFT). Degree of crystallinity/non-crystallinity was measured by X-ray powder diffraction (XRPD). Phase behavior was measured by differential scanning calorimetry. The chemical composition by molecular fingerprinting was established using attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy. The amount of AmB loaded into the proliposomes was quantified using UV-VIS spectroscopy. The in vitro aerosol dispersion performance was conducted using the Next Generation Impactor (NGI) and the human dry powder inhaler (DPI) (Handihaler®) that is FDA-approved. Different human lung cell lines were employed to demonstrate in vitro safety as a function of dose and formulation. Smooth, spherical microparticles/nanoparticles were formed at medium and high spray drying pump rates and had low residual water content. A characteristic peak in the XRPD diffraction pattern as well as an endotherm in DSC confirmed the presence of the lipid bilayer structure characteristic in the DPPC/DPPG proliposomal systems. Superior in vitro aerosol performance was achieved with engineered microparticles/nanoparticles demonstrating suitability for targeted pulmonary drug delivery as inhalable dry powders. The in vitro cellular studies demonstrated that the formulated proliposomes are safe. These AmB proliposomes can be a better option for targeted treatment of severe pulmonary fungal infections. SN - 1522-9629 UR - https://www.unboundmedicine.com/medline/citation/33137515/Advanced_spray_dried_proliposomes_of_amphotericin_B_lung_surfactant_mimic_phospholipid_microparticles/nanoparticles_as_dry_powder_inhalers_for_targeted_pulmonary_drug_delivery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(20)30180-2 DB - PRIME DP - Unbound Medicine ER -