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The design and delivery of a biodegr...
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The University of Wisconsin - Madison.
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The design and delivery of a biodegradable poly(lactic-co-glycolic) acid based carrier to the regional lymphatics in rats.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
The design and delivery of a biodegradable poly(lactic-co-glycolic) acid based carrier to the regional lymphatics in rats./
Author:
Rao, Deepa Avasarala.
Description:
195 p.
Notes:
Adviser: Joseph R. Robinson.
Contained By:
Dissertation Abstracts International69-09B.
Subject:
Chemistry, Pharmaceutical. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3327754
ISBN:
9780549799818
The design and delivery of a biodegradable poly(lactic-co-glycolic) acid based carrier to the regional lymphatics in rats.
Rao, Deepa Avasarala.
The design and delivery of a biodegradable poly(lactic-co-glycolic) acid based carrier to the regional lymphatics in rats.
- 195 p.
Adviser: Joseph R. Robinson.
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2008.
The lymphatic system has been shown to be involved in cancer metastasis and HIV. However, very little research has been done so far to successfully target drugs to the lymphatic system due to a fundamental gap in understanding the relevant characteristics needed for a carrier system. The purpose of our research is to evaluate different biodegradable drug carrier systems on the basis of size, hydrophobicity and charge distribution that would lead to preferential uptake and retention into the regional lymphatics. The first aim was to create tagged biodegradable particles of defined size, hydrophobicity and charge density. The second aim was to test these particles in a rat model to determine their ability to locate within the regional lymphatics.
ISBN: 9780549799818Subjects--Topical Terms:
550957
Chemistry, Pharmaceutical.
The design and delivery of a biodegradable poly(lactic-co-glycolic) acid based carrier to the regional lymphatics in rats.
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The design and delivery of a biodegradable poly(lactic-co-glycolic) acid based carrier to the regional lymphatics in rats.
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195 p.
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Adviser: Joseph R. Robinson.
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Source: Dissertation Abstracts International, Volume: 69-09, Section: B, page: 5424.
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Thesis (Ph.D.)--The University of Wisconsin - Madison, 2008.
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The lymphatic system has been shown to be involved in cancer metastasis and HIV. However, very little research has been done so far to successfully target drugs to the lymphatic system due to a fundamental gap in understanding the relevant characteristics needed for a carrier system. The purpose of our research is to evaluate different biodegradable drug carrier systems on the basis of size, hydrophobicity and charge distribution that would lead to preferential uptake and retention into the regional lymphatics. The first aim was to create tagged biodegradable particles of defined size, hydrophobicity and charge density. The second aim was to test these particles in a rat model to determine their ability to locate within the regional lymphatics.
520
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The polymer poly(lactic-co-glycolic) acid (PLGA) was chosen as the biodegradable scaffold and it was successfully conjugated to 1-pyrenemethylamine (PMA). PLGA-PMA was co-precipitated with poly lactic-b-polyethyleneglycol to obtain low hydrophobicity nanoparticles of 50, 100 and 200 nm sizes. The uptake and retention of these particles was compared to high hydrophobicity fluorescently labeled polystyrene particles of 60, 112 and 200 nm. Particles of 50 nm size with varying surface charge were prepared by co-precipitating PLGA-PMA with acid end group PLGA at ratios of 80:20, 50:50 and 20:80 with the anionic charge distribution going from the least to the highest.
520
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The in vivo size study showed 50 followed by 100 and 200 nm particles having statistically high regional accumulation. Statistically it was also seen that as the hydrophobicity of the particle increases, the uptake and retention of these particles decreases irrespective of the size. The charge study revealed that as the anionic charge distribution increases so does the lymphatic uptake and retention in a statistically significant manner.
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Overall conclusions from the work indicate that 50 nm particles with low hydrophobicity can act as the primary scaffold for delivery into the regional lymphatics. Results from the charge study indicate that the most anionically charged particle can be used for dissemination within the lymphatics. However macrophage involvement in the uptake and retention of these particles needs to be evaluated prior to proceeding further.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3327754
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