Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing a Prolonged Drug Level in Lungs: A Promise for Treating Fungal Infection.
Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design, development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labeling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC-MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles.
†Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam-786004, India.
Pranab Jyoti
PJ
Das
§Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, West Bengal, India.
Paramita
P
Paul
§Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, West Bengal, India.
Biswajit
B
Mukherjee
†Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam-786004, India.
Bhaskar
B
Mazumder
§Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, West Bengal, India.
Laboni
L
Mondal
∥Infectious and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata-700032, India.
Rinku
R
Baishya
∥Infectious and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata-700032, India.
Mita Chatterjee
MC
Debnath
⊥Guwahati Biotech Park, Technology Complex, Indian Institute of Technology, Guwahati-781039, India.
Kumar Saurav
KS
Dey
D000280:Administration, Inhalation; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D004337:Drug Carriers; D005260:Female; D006207:Half-Life; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D004337:Drug Carriers; D011100:Polyglycolic Acid; D065819:Voriconazole
biodistribution; clearance; gamma imaging; lungs; nanoparticles; pulmonary drug delivery; radiolabeling