Biodistribution and histopathology studies of amphotericin B sodium deoxycholate sulfate formulation following intratracheal instillation in rat models

Drug Delivery and Translational Research
Faisal UsmanTeerapol Srichana

Abstract

Aerosol inhalation of amphotericin B (AmB) can be a clinically compliant way to administer the drug directly to the pulmonary route for treatment as well as prophylaxis of invasive pulmonary aspergillosis (IPA). We report aerosol formulation of AmB using sodium deoxycholate sulfate (SDCS), a lipid carrier synthesized in-house using natural precursor deoxycholic acid. In vitro toxicity was determined by MTT assay. Biodistribution and histopathology in rats were evaluated in targeted organs including the lungs, kidneys, spleen, and liver. No toxicity was observed when lung and kidney cells treated with AmB-SDCS formulations up to 8 μg/mL and minimal toxicity at higher concentration 16 μg/mL, while the Fungizone®-like formulation induced toxicity to lung and kidney cells with viability decreasing from 86 to 41% and 100 to 49%, respectively, when compared with an equivalent concentration of AmB-SDCS. Renal and hepatic markers were raised for Fungizone®-like formulation-treated rats but not for AmB-SDCS formulations following 7 days of regular dosing by intratracheal instillation. AmB concentrations were highest in the lungs (5.4-8.3 μg/g) which were well above minimum inhibitory concentration (MIC) of all Aspergillus species. Plasm...Continue Reading

References

Apr 1, 1991·Antimicrobial Agents and Chemotherapy·J M ClarkD P Bonner
Aug 1, 1995·The European Respiratory Journal·P DiotG C Smaldone
Sep 1, 1995·Chest·J DuboisM R Pratter
Feb 1, 1993·American Journal of Clinical Oncology·J GrynJ Inzerillo
Feb 1, 1997·Antimicrobial Agents and Chemotherapy·C E CicognaD Armstrong
May 1, 1997·Antimicrobial Agents and Chemotherapy·R BhamraC E Swenson
Sep 19, 1997·Journal of Pharmaceutical Sciences·M P LambrosD L Johnson
Jun 13, 1998·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·D W Denning
Sep 19, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·B G YuG Kwon
Jan 22, 2002·The Journal of Antimicrobial Chemotherapy·Bertrand Dupont
May 1, 2002·Current Opinion in Pulmonary Medicine·Ilana Oren, Noam Goldstein
Dec 31, 2003·International Journal of Pharmaceutics·S P VyasParamjit Singh
May 12, 2005·International Journal of Pharmaceutics·Suresh P VyasK S Jaganathan
Sep 10, 2005·American Journal of Respiratory and Critical Care Medicine·Svetlana GelperinaLeonid Heifets
Sep 27, 2006·International Journal of Pharmaceutics·Waree Tiyaboonchai, Nanteetip Limpeanchob
Sep 26, 2007·Journal of Pharmaceutical Sciences·J J TorradoS Torrado-Santiago
Jan 8, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Thomas J WalshUNKNOWN Infectious Diseases Society of America
Jun 6, 2009·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Suk Hyun JungByung Cheol Shin
Jan 1, 2009·Critical Reviews in Therapeutic Drug Carrier Systems·Anu PuriRobert Blumenthal
Feb 27, 2013·International Journal of Pharmaceutics·Dolores R SerranoJuan J Torrado
Apr 16, 2014·Biomedical Chromatography : BMC·Bushra T Al-QuadeibAbdulaziz Alshaer
Aug 26, 2014·International Journal of Pharmaceutics·Mengyu ZhaoZibin Gao
Feb 11, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Leila Rodrigues CaldeiraLucas Antônio Miranda Ferreira

❮ Previous
Next ❯

Citations

Jan 8, 2020·Pharmaceutics·Célia Faustino, Lídia Pinheiro
Jun 25, 2020·BMC Pulmonary Medicine·Shanjana AwasthiStanley Kosanke

❮ Previous
Next ❯

Methods Mentioned

BETA
pharmacotherapy
dynamic light scattering

Software Mentioned

SPSS
cellSens

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.