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Development of a specific pulmonary ...

Zhou, Huiyu.

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Development of a specific pulmonary sustained delivery system for isoniazid.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Development of a specific pulmonary sustained delivery system for isoniazid./
作者:	Zhou, Huiyu.
面頁冊數:	92 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1419.
Contained By:	Dissertation Abstracts International66-03B.
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3168669
ISBN:	0542050781

Development of a specific pulmonary sustained delivery system for isoniazid.
Zhou, Huiyu.

Development of a specific pulmonary sustained delivery system for isoniazid. - 92 p.

Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1419.

Thesis (Ph.D.)--University of Colorado Health Sciences Center, 2005.

To improve patient's compliance with existing chemotherapy for tuberculosis (TB), we developed a microsphere-based drug delivery system to target a model anti-TB drug, isoniazid (INH), to alveolar macrophages (AMs) and to provide sustained drug release.

ISBN: 0542050781Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Development of a specific pulmonary sustained delivery system for isoniazid.
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245 1 0 $a Development of a specific pulmonary sustained delivery system for isoniazid.
300 $a 92 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-03, Section: B, page: 1419.
500 $a Director: Ka-yun Lawrence Ng.
502 $a Thesis (Ph.D.)--University of Colorado Health Sciences Center, 2005.
520 $a To improve patient's compliance with existing chemotherapy for tuberculosis (TB), we developed a microsphere-based drug delivery system to target a model anti-TB drug, isoniazid (INH), to alveolar macrophages (AMs) and to provide sustained drug release.
520 $a To incorporate the polar yet neutral compound, INH, into biodegradable PLA polymers, we used a two-step approach wherein a negatively charged prodrug of INH, isoniazid methanesulfonate (INHMS), was first synthesized, followed by ion-pairing of INHMS with hydrophobic cations to form hydrophobic species of the drug. The hydrophobic ion-paired complexes of INHMS (HIP-INHMS) were then incorporated in biodegradable PLA polymers using precipitation with a compressed antisolvent (PCA). The drug/polymer particles produced were spherical with a size in the range from 1 to 3 mum in diameter, ideal for deep lung penetration. In vitro release profiles in phosphate-buffered saline showed an initial burst followed by a sustained release of the drug over ten days. Neither the choice of hydrophobic cations nor the environmental pH seemed to affect the release kinetics.
520 $a To evaluate the drug-loaded PLA microspheres in vivo, we developed and validated a sensitive assay using liquid chromatography - tandem mass spectrometry (LC/LC-MS/MS) for quantification of INH and its major metabolite, acetylisoniazid (AcINH), in plasma and AMs of rats. Using this assay, high levels of INH was detected in NR8383, a rat AM cell line, after the cells were exposed to drug-loaded microspheres. To confirm the microparticles can target AMs in vivo, we compared the INH levels in bronchoalveolar lavaged (BAL) macrophages by LC/MS/MS after the Sprague-Dawley rats were administered either INHMS-loaded PLA microspheres by intra-tracheal instillation or INH aqueous solution by gavage or intra-tracheal instillation. As expected, only microparticles provided sustained and targeted delivery of INH to AMs. Most importantly, this method of delivery led to substantial reduction in the blood levels of acetylisoniazid (AcINH), a major and potential toxic metabolite of INH.
520 $a Our work suggests that PLA microspheres prepared using PCA process offer promises for treating pulmonary TB with reduced doses, lower dosing frequency and alleviated toxicity.
590 $a School code: 0831.
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Chemistry, Pharmaceutical. $3 550957
690 $a 0572
690 $a 0491
710 2 0 $a University of Colorado Health Sciences Center. $3 1023815
773 0 $t Dissertation Abstracts International $g 66-03B.
790 1 0 $a Ng, Ka-yun Lawrence, $e advisor
790 $a 0831
791 $a Ph.D.
792 $a 2005
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