dc.contributor.author | Day, Timothy P. | |
dc.contributor.author | Sil, Diptesh | |
dc.contributor.author | Shukla, Nikunj M. | |
dc.contributor.author | Anbanandam, Asokan | |
dc.contributor.author | Day, Victor W. | |
dc.contributor.author | David, Sunil A. | |
dc.date.accessioned | 2017-05-09T19:40:40Z | |
dc.date.available | 2017-05-09T19:40:40Z | |
dc.date.issued | 2011-02-07 | |
dc.identifier.citation | Day, T. P., Sil, D., Shukla, N. M., Anbanandam, A., Day, V. W., & David, S. A. (2011). Imbuing Aqueous Solubility to Amphotericin B and Nystatin with a Vitamin. Molecular Pharmaceutics, 8(1), 297–301. http://doi.org/10.1021/mp100363f | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24054 | |
dc.description.abstract | Aqueous solubilities of many drugs in current clinical use are very low, necessitating formulations that often present problems for parenteral administration, including toxicities due to the excipients used. Recognizing that pharmacologically active compounds frequently possess amines, we asked whether pyridoxal phosphate (PLP), an inoccuous, water-soluble vitamin, could be utilized to form prodrug-like complexes via the formation of imine or iminium adducts, and whether the vitamin would impart solubilizing properties to such complexes. Direct spectroscopic and crystallographic data obtained using model primary and secondary amines showed that PLP forms stable imine adducts with primary amines under entirely aqueous conditions and at physiologic pH, while no reaction was observed for secondary amines; the basis of the exceptional stability appears to be a consequence of favorable H-bond interactions of the imine nitrogen with the 5-OH group of PLP. Amphotericin B and nystatin in their native forms display marked aqueous insolubility, and possess lone primary amines. We were able to utilize PLP in achieving excellent solubilization of both these antifungal agents, surpassing aqueous solubilities of 100 mg/mL. In in vitro bioassays, both polyenes in their PLP-adducted form display attenuated antifungal potencies which is attributable to ‘prodrug-like’ complexes. These results point to the utility of excipient-free, entirely aqueous formulations of amphotericin B for parenteral use, and may also be extended to other primary amine-bearing compounds exhibiting poor aqueous solubility. | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/mp100363f. | en_US |
dc.subject | Amphotericin B | en_US |
dc.subject | Nystatin | en_US |
dc.subject | Pyridoxal phosphate | en_US |
dc.subject | Aqueous solubilization | en_US |
dc.title | Imbuing Aqueous Solubility to Amphotericin B and Nystatin with a Vitamin | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Day, Timothy P. | |
kusw.kuauthor | Sil, Diptesh | |
kusw.kuauthor | Shukla, Nikunj M. | |
kusw.kuauthor | Anbanandam, Asokan | |
kusw.kuauthor | Day, Victor W. | |
kusw.kuauthor | David, Sunil A. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1021/mp100363f | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-6457-0545 | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3034802 | en_US |
dc.rights.accessrights | openAccess | |