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Effects of nonionic surfactants on n...

Croy, Scott R.

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Effects of nonionic surfactants on nystatin aggregation state and toxicity.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Effects of nonionic surfactants on nystatin aggregation state and toxicity./
Author:	Croy, Scott R.
Description:	162 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2534.
Contained By:	Dissertation Abstracts International66-05B.
Subject:	Health Sciences, Pharmacy. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3175492
ISBN:	9780542140389

Effects of nonionic surfactants on nystatin aggregation state and toxicity.
Croy, Scott R.

Effects of nonionic surfactants on nystatin aggregation state and toxicity. - 162 p.

Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2534.

Thesis (Ph.D.)--The University of Wisconsin - Madison, 2005.

This dissertation covered formulation of the antifungal drug nystatin by nonionic surfactant micelles. Nystatin is an amphiphilic and amphoteric molecule that aggregates in aqueous media. Unimers of nystatin show strong selectivity for fungal cell membranes, where they exert their activity. However, aggregates are not selective and are able to cause damage to fungal and mammalian cell membranes. It was proposed that nonionic surfactant micelles could prevent or reduce the aggregation, and therefore the toxicity, of nystatin by improvement in its solubilization at the micellar core. Surfactants studied included the class known as poloxamers, as well as CrEL and polysorbate 80. These surfactants were studied for abilities to prevent toxic aggregation of nystatin based on their physical properties. It was determined by dynamic light scattering that surfactant micelles were able to effectively prevent the aggregation of nystatin. Key characteristics responsible for the extent of nystatin deaggregation possible for the surfactants were defined by fluorescence methods as well as location of the nystatin molecules in surfactant micelles. It was determined that nystatin is solubilized at the micelle core-corona interface, and that the number of micelles in solution and core surface area accessible to the drug are the primary factors driving solubilization. Additionally, multiple unique assays indicated the surfactants were able to attenuate nystatin aggregate induced toxicities in highly relevant cell culture lines, including erythrocytes, human kidney cells, and human monocytes. Lastly, toxicity and pharmacokinetics of the formulations were analyzed in vivo, and efficacy of the nystatin formulations was also studied both in vitro and in vivo in a murine model of disseminated candidiasis.

ISBN: 9780542140389Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Effects of nonionic surfactants on nystatin aggregation state and toxicity.
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500 $a Source: Dissertation Abstracts International, Volume: 66-05, Section: B, page: 2534.
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502 $a Thesis (Ph.D.)--The University of Wisconsin - Madison, 2005.
520 $a This dissertation covered formulation of the antifungal drug nystatin by nonionic surfactant micelles. Nystatin is an amphiphilic and amphoteric molecule that aggregates in aqueous media. Unimers of nystatin show strong selectivity for fungal cell membranes, where they exert their activity. However, aggregates are not selective and are able to cause damage to fungal and mammalian cell membranes. It was proposed that nonionic surfactant micelles could prevent or reduce the aggregation, and therefore the toxicity, of nystatin by improvement in its solubilization at the micellar core. Surfactants studied included the class known as poloxamers, as well as CrEL and polysorbate 80. These surfactants were studied for abilities to prevent toxic aggregation of nystatin based on their physical properties. It was determined by dynamic light scattering that surfactant micelles were able to effectively prevent the aggregation of nystatin. Key characteristics responsible for the extent of nystatin deaggregation possible for the surfactants were defined by fluorescence methods as well as location of the nystatin molecules in surfactant micelles. It was determined that nystatin is solubilized at the micelle core-corona interface, and that the number of micelles in solution and core surface area accessible to the drug are the primary factors driving solubilization. Additionally, multiple unique assays indicated the surfactants were able to attenuate nystatin aggregate induced toxicities in highly relevant cell culture lines, including erythrocytes, human kidney cells, and human monocytes. Lastly, toxicity and pharmacokinetics of the formulations were analyzed in vivo, and efficacy of the nystatin formulations was also studied both in vitro and in vivo in a murine model of disseminated candidiasis.
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