Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery
Invasive Pulmonary Aspergillosis (IPA) and <i>Pneumocystis jiroveci</i> Pneumonia (PCP) are serious fungal pulmonary diseases for immunocompromised patients. The brand name drug CANCIDAS<sup>®</sup> (Caspofungin acetate for injection) is FDA approved to treat IPA, but is only...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/4/504 |
| _version_ | 1797538636988678144 |
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| author | Iching G. Yu David M. Ryckman |
| author_facet | Iching G. Yu David M. Ryckman |
| author_sort | Iching G. Yu |
| collection | DOAJ |
| description | Invasive Pulmonary Aspergillosis (IPA) and <i>Pneumocystis jiroveci</i> Pneumonia (PCP) are serious fungal pulmonary diseases for immunocompromised patients. The brand name drug CANCIDAS<sup>®</sup> (Caspofungin acetate for injection) is FDA approved to treat IPA, but is only 40% effective. Efficacious drug levels at the lung infection site are not achieved by systemic administration. Increasing the dose leads to toxicity. The objective, here, is to reformulate caspofungin for aerosolization to high drug concentration by lung targeted delivery and avoid systemic distribution. Described in this paper is a new, room temperature-stable formulation that meets these goals. The in vitro antifungal activity, solid state and reconstituted stability, and aerosol properties of the new formulation are presented. In addition, pharmacokinetic parameters and tissue distribution data are determined from nose-only inhalation studies in rats. Plasma and tissue samples were analyzed by High Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS-MS). Inhaled drug concentrations for caspofungin Active Pharmaceutical Ingredient (API), and the new formulation, were compared at the same dose. In the lungs, the parameters C<sub>max</sub> and Area Under Curve (AUC) showed a 70%, and 60%, respective increase in drug deposition for the new formulation without significant systemic distribution. Moreover, the calculated pharmacodynamic indices suggest an improvement in efficacy. These findings warrant further animal toxicology studies and human clinical trials, with inhaled caspofungin, for treating IPA. |
| first_indexed | 2024-03-10T12:33:15Z |
| format | Article |
| id | doaj.art-d6211e8b8be5419697662c3fde49da56 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T12:33:15Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d6211e8b8be5419697662c3fde49da562023-11-21T14:29:15ZengMDPI AGPharmaceutics1999-49232021-04-0113450410.3390/pharmaceutics13040504Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary DeliveryIching G. Yu0David M. Ryckman1Trilogy Therapeutics, Inc., San Diego, CA 92130, USATrilogy Therapeutics, Inc., San Diego, CA 92130, USAInvasive Pulmonary Aspergillosis (IPA) and <i>Pneumocystis jiroveci</i> Pneumonia (PCP) are serious fungal pulmonary diseases for immunocompromised patients. The brand name drug CANCIDAS<sup>®</sup> (Caspofungin acetate for injection) is FDA approved to treat IPA, but is only 40% effective. Efficacious drug levels at the lung infection site are not achieved by systemic administration. Increasing the dose leads to toxicity. The objective, here, is to reformulate caspofungin for aerosolization to high drug concentration by lung targeted delivery and avoid systemic distribution. Described in this paper is a new, room temperature-stable formulation that meets these goals. The in vitro antifungal activity, solid state and reconstituted stability, and aerosol properties of the new formulation are presented. In addition, pharmacokinetic parameters and tissue distribution data are determined from nose-only inhalation studies in rats. Plasma and tissue samples were analyzed by High Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS-MS). Inhaled drug concentrations for caspofungin Active Pharmaceutical Ingredient (API), and the new formulation, were compared at the same dose. In the lungs, the parameters C<sub>max</sub> and Area Under Curve (AUC) showed a 70%, and 60%, respective increase in drug deposition for the new formulation without significant systemic distribution. Moreover, the calculated pharmacodynamic indices suggest an improvement in efficacy. These findings warrant further animal toxicology studies and human clinical trials, with inhaled caspofungin, for treating IPA.https://www.mdpi.com/1999-4923/13/4/504inhalationpulmonary drug deliverycaspofunginantifungalformulationpeptide(s) |
| spellingShingle | Iching G. Yu David M. Ryckman Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery Pharmaceutics inhalation pulmonary drug delivery caspofungin antifungal formulation peptide(s) |
| title | Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery |
| title_full | Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery |
| title_fullStr | Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery |
| title_full_unstemmed | Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery |
| title_short | Assessment and Development of the Antifungal Agent Caspofungin for Aerosolized Pulmonary Delivery |
| title_sort | assessment and development of the antifungal agent caspofungin for aerosolized pulmonary delivery |
| topic | inhalation pulmonary drug delivery caspofungin antifungal formulation peptide(s) |
| url | https://www.mdpi.com/1999-4923/13/4/504 |
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