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
AU - Mansour, Heidi M.
N1 - Funding Information:
The authors gratefully acknowledge financial support from Western Alliance to Expand Student Opportunities (WAESO) Louis Stokes Alliance for Minority Participation (LSAMP) National Science Foundation ( NSF ) Cooperative Agreement No. HRD-1101728 and UA UROC-PREP and NSF WAESO to AIG and HMM. This work was partially supported by NIH NIAID HHSN2272201000033I/HHSN27200002 A65 (HMM) and NIH NHLBI 1R01HL137282 (HMM and SMB ) and a CONACyT Fellowship awarded to MFA . This material is based upon work supported by the National Science Foundation under Grant Number #0619599 and Arizona Proposition 301: Technology and Research Initiative Fund (A.R.S.§15–1648).
Funding Information:
SEM images and data were collected in the W.M. Keck Center for Nano-Scale Imaging in the Department of Chemistry and Biochemistry at the University of Arizona with funding from the W.M. Keck Foundation Grant. Raman data was collected in the Imaging Cores - Materials Imaging and Characterization Facility supported by the office of Research, Discovery and Innovation at the University of Arizona . This material is based upon work supported by the National Science Foundation under Grant Number #0619599 and Arizona Proposition 301: Technology and Research Initiative Fund (A.R.S.§15–1648). X-ray diffraction data were collected in the X-Ray Diffraction Facility of the Department of Chemistry and Biochemistry, The University of Arizona. The authors sincerely thank Dr. Brooke Beam-Masani, Dr. Andrei Astachkine, Dr. Chad Park for the core facility access, assistance and Dr. Nathan Cherrington for access to the UV-microplate reader.
Funding Information:
The authors gratefully acknowledge financial support from Western Alliance to Expand Student Opportunities (WAESO) Louis Stokes Alliance for Minority Participation (LSAMP) National Science Foundation (NSF) Cooperative Agreement No. HRD-1101728 and UA UROC-PREP and NSF WAESO to AIG and HMM. This work was partially supported by NIH NIAID HHSN2272201000033I/HHSN27200002 A65 (HMM) and NIH NHLBI 1R01HL137282 (HMM and SMB) and a CONACyT Fellowship awarded to MFA. This material is based upon work supported by the National Science Foundation under Grant Number #0619599 and Arizona Proposition 301: Technology and Research Initiative Fund (A.R.S.?15?1648).SEM images and data were collected in the W.M. Keck Center for Nano-Scale Imaging in the Department of Chemistry and Biochemistry at the University of Arizona with funding from the W.M. Keck Foundation Grant. Raman data was collected in the Imaging Cores - Materials Imaging and Characterization Facility supported by the office of Research, Discovery and Innovation at the University of Arizona. This material is based upon work supported by the National Science Foundation under Grant Number #0619599 and Arizona Proposition 301: Technology and Research Initiative Fund (A.R.S.?15?1648). X-ray diffraction data were collected in the X-Ray Diffraction Facility of the Department of Chemistry and Biochemistry, The University of Arizona. The authors sincerely thank Dr. Brooke Beam-Masani, Dr. Andrei Astachkine, Dr. Chad Park for the core facility access, assistance and Dr. Nathan Cherrington for access to the UV-microplate reader.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/10
Y1 - 2020/10
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.
AB - 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.
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
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U2 - 10.1016/j.pupt.2020.101975
DO - 10.1016/j.pupt.2020.101975
M3 - Article
C2 - 33137515
AN - SCOPUS:85095446542
SN - 1094-5539
VL - 64
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
M1 - 101975
ER -