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Synthesis and characterization of DN...
~
Enriquez Schumacher, Iris Vanessa.
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Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy./
作者:
Enriquez Schumacher, Iris Vanessa.
面頁冊數:
278 p.
附註:
Source: Dissertation Abstracts International, Volume: 70-11, Section: B, page: 7140.
Contained By:
Dissertation Abstracts International70-11B.
標題:
Engineering, Biomedical. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3381377
ISBN:
9781109453423
Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy.
Enriquez Schumacher, Iris Vanessa.
Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy.
- 278 p.
Source: Dissertation Abstracts International, Volume: 70-11, Section: B, page: 7140.
Thesis (Ph.D.)--University of Florida, 2007.
Conventional cancer chemotherapy results in systemic toxicity which severely limits effectiveness and often adversely affects patient quality of life. There is a need to find new drugs and delivery methods for less toxic therapy.
ISBN: 9781109453423Subjects--Topical Terms:
1017684
Engineering, Biomedical.
Synthesis and characterization of DNA nano-meso-microspheres as drug delivery carriers for intratumoral chemotherapy.
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Conventional cancer chemotherapy results in systemic toxicity which severely limits effectiveness and often adversely affects patient quality of life. There is a need to find new drugs and delivery methods for less toxic therapy.
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Previous studies concerning DNA complexing with chemotherapy drugs suggest unique opportunities for DNA as a mesosphere drug carrier. The overall objective of this research was devoted to the synthesis and evaluation of novel DNA-drug nano-mesospheres designed for localized chemotherapy via intratumoral injection. My research presents DNA nano-meso-microspheres (DNA-MS) that were prepared using a modified steric stabilization method originally developed in this lab for the preparation of albumin MS. DNA-MS were prepared with glutaraldehyde covalent crosslinking (genipin crosslinking was attempted) through the DNA base pairs. In addition, novel crosslinking of DNA-MS was demonstrated using chromium, gadolinium, or iron cations through the DNA phosphate groups. Covalent and ionic crosslinked DNA-MS syntheses yielded smooth and spherical particle morphologies with multimodal size distributions.
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Optimized DNA-MS syntheses produced particles with narrow and normal size distributions in the 50nm to 5mum diameter size range. In aqueous dispersions approximately 200% swelling was observed with dispersion stability for more than 48 hours. Typical process conditions included a 1550rpm initial mixing speed and particle filtration through 20mum filters to facilitate preparation.
520
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DNA-MS were in situ loaded during synthesis for the first time with mitoxantrone, 5-fluorouracil, and methotrexate. DNA-MS drug incorporation was 12%(w/w) for mitoxantrone, 9%(w/w) for methotrexate, and 5%(w/w) for 5-fluorouracil. In vitro drug release into phosphate buffered saline was observed for over 35 days by minimum sink release testing. The effect of gadolinium crosslink concentration on mitoxantrone release was evaluated at molar equivalences in the range of 20% to 120%. The most highly crosslinked DNA-MS exhibited the longest sustained release.
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The drug efficacy of mitoxantrone loaded DNA-MS was evaluated in vitro using a murine Lewis lung carcinoma cell line and a significant cytotoxic response was found at mitoxantrone doses as low as 1ppm. Drug release properties, DNA biodegradability, and observed cancer cell cytotoxicity of drug loaded DNA-MS suggest that they are appropriate for intratumoral chemotherapy evaluation aimed at improved and less toxic cancer therapy.
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