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Salicylate based poly(anhydride-este...

Yeagy, Brian Allen.

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Salicylate based poly(anhydride-ester) microspheres: Preparation, in vitro and in vivo characterization.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Salicylate based poly(anhydride-ester) microspheres: Preparation, in vitro and in vivo characterization./
作者:	Yeagy, Brian Allen.
面頁冊數:	155 p.
附註:	Adviser: Thomas J. Cook.
Contained By:	Dissertation Abstracts International68-02B.
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3253029

Salicylate based poly(anhydride-ester) microspheres: Preparation, in vitro and in vivo characterization.
Yeagy, Brian Allen.

Salicylate based poly(anhydride-ester) microspheres: Preparation, in vitro and in vivo characterization. - 155 p.

Adviser: Thomas J. Cook.

Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 2007.

The aim of this project was to investigate solvent evaporation/extraction as a method to formulate salicylate-based poly(anhydride-esters) into microspheres and to characterize them for intestinal delivery applications (e.g. inflammatory bowel disease (IBD) treatment). The salicylate-based poly(anhydride-esters) studied were poly[1,6-bis(o-carboxyphenoxy)hexanoate] (CPH), poly[1,8-bis(o-carboxyphenoxy)octanoate] (CPO) poly[1,10-bis( o-carboxyphenoxy)decanoate] (CPD), 5-(2,4-difluorophenyl) polymer (poly(diflunisal), salicylsalicylic polymer (poly(salsalate), and 5-acetamidosalicylic polymer (poly(5-ASA). A modified oil-in-water solvent evaporation method was optimized for preparing microspheres of the polymers by altering several of the parameters including: emulsion mechanism, method of microsphere isolation, and the concentration of aqueous surfactant. The poly(anhydride-ester) microspheres were investigated for the factors involved in the change in glass transition temperature (Tg) observed after microsphere formulation, physiochemical properties, salicylate release, and in vitro degradation. CPH and poly(diflunisal) microspheres were selected for in situ evaluation in order to determine the effect that poly(anhydride-ester) microsphere properties have on uptake in the ileum and colon of rats. Scanning electron microscopic analysis of the microspheres revealed that polymer Tg and organic solubility were critical for microsphere formation. After formulation, the microspheres exhibited changes in Tg compared to their polymer precursor. The major contributors to the change in Tg after microsphere formulation were linker length, structural composition, and molecular weight (MW). The hydrophobicity of the poly(anhydride-esters) was determined to be influenced by MW and polymer composition, and microsphere size distribution modes by polymer age, homogenization speed, MW, as well as the polymer's structural composition. Salicylate release was observed to be decreased by increasing the length of the diacyl polymer linker, and the polymers MW. Altering the microspheres composition by incorporating the different salicylates into the poly(anhydride-esters) resulted in changing both the release profiles as well as their initial release kinetics. In situ studies of poly(anhydride-ester) microspheres uptake by rat ileum and colon indicated that the intestinal uptake of the microspheres was polymer, and tissue dependent. Microsphere uptake occurred by mucal adhesion and/or epithelial transcytosis, and ileal Peyer's patches had higher microsphere uptake compare the non-Peyer's patch ileum, and colon tissue. Overall, these result indicate that salicylate-based poly(anhydride-ester) microspheres have potential for IBD treatment.Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Salicylate based poly(anhydride-ester) microspheres: Preparation, in vitro and in vivo characterization.
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245 1 0 $a Salicylate based poly(anhydride-ester) microspheres: Preparation, in vitro and in vivo characterization.
300 $a 155 p.
500 $a Adviser: Thomas J. Cook.
500 $a Source: Dissertation Abstracts International, Volume: 68-02, Section: B, page: 0913.
502 $a Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick, 2007.
520 $a The aim of this project was to investigate solvent evaporation/extraction as a method to formulate salicylate-based poly(anhydride-esters) into microspheres and to characterize them for intestinal delivery applications (e.g. inflammatory bowel disease (IBD) treatment). The salicylate-based poly(anhydride-esters) studied were poly[1,6-bis(o-carboxyphenoxy)hexanoate] (CPH), poly[1,8-bis(o-carboxyphenoxy)octanoate] (CPO) poly[1,10-bis( o-carboxyphenoxy)decanoate] (CPD), 5-(2,4-difluorophenyl) polymer (poly(diflunisal), salicylsalicylic polymer (poly(salsalate), and 5-acetamidosalicylic polymer (poly(5-ASA). A modified oil-in-water solvent evaporation method was optimized for preparing microspheres of the polymers by altering several of the parameters including: emulsion mechanism, method of microsphere isolation, and the concentration of aqueous surfactant. The poly(anhydride-ester) microspheres were investigated for the factors involved in the change in glass transition temperature (Tg) observed after microsphere formulation, physiochemical properties, salicylate release, and in vitro degradation. CPH and poly(diflunisal) microspheres were selected for in situ evaluation in order to determine the effect that poly(anhydride-ester) microsphere properties have on uptake in the ileum and colon of rats. Scanning electron microscopic analysis of the microspheres revealed that polymer Tg and organic solubility were critical for microsphere formation. After formulation, the microspheres exhibited changes in Tg compared to their polymer precursor. The major contributors to the change in Tg after microsphere formulation were linker length, structural composition, and molecular weight (MW). The hydrophobicity of the poly(anhydride-esters) was determined to be influenced by MW and polymer composition, and microsphere size distribution modes by polymer age, homogenization speed, MW, as well as the polymer's structural composition. Salicylate release was observed to be decreased by increasing the length of the diacyl polymer linker, and the polymers MW. Altering the microspheres composition by incorporating the different salicylates into the poly(anhydride-esters) resulted in changing both the release profiles as well as their initial release kinetics. In situ studies of poly(anhydride-ester) microspheres uptake by rat ileum and colon indicated that the intestinal uptake of the microspheres was polymer, and tissue dependent. Microsphere uptake occurred by mucal adhesion and/or epithelial transcytosis, and ileal Peyer's patches had higher microsphere uptake compare the non-Peyer's patch ileum, and colon tissue. Overall, these result indicate that salicylate-based poly(anhydride-ester) microspheres have potential for IBD treatment.
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