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Novel Folic Acid Targeted Nanomicell...

Shah, Sujay.

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Novel Folic Acid Targeted Nanomicelles for Delivery of Hydrophobic Drugs to the Back of the Eye.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Novel Folic Acid Targeted Nanomicelles for Delivery of Hydrophobic Drugs to the Back of the Eye./
Author:	Shah, Sujay.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	162 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Contained By:	Dissertations Abstracts International80-12B.
Subject:	Chemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13885993
ISBN:	9781392231906

Novel Folic Acid Targeted Nanomicelles for Delivery of Hydrophobic Drugs to the Back of the Eye.
Shah, Sujay.

Novel Folic Acid Targeted Nanomicelles for Delivery of Hydrophobic Drugs to the Back of the Eye. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 162 p.

Source: Dissertations Abstracts International, Volume: 80-12, Section: B.

Thesis (Ph.D.)--University of Missouri - Kansas City, 2019.

This item must not be added to any third party search indexes.

Overall aim of this research project is to develop folic acid targeted nanomicelles loaded with insoluble hydrophobic drugs for delivery to posterior segment of the eye. Retinoblastoma and uveitis are diseases that affect the posterior segment. Etoposide (ET) is used for treatment of retinoblastoma and fluocinolone acetonide (FA) is used for treatment of uveitis. Both drugs have very poor water solubility and it is necessary to develop clear aqueous solutions for topical drug delivery. We utilized vitamin E TPGS polymer to develop nanomicelles to solubilize the drugs. The polymer was also modified with PEG chain having molecular weight of 2000. Synthesis of modified polymer was performed and confirmed by NMR studies. Critical micelle concentration of modified polymer was determined using pyrene method. The size of drug loaded nanomicelles was < 20nm. Nanomicelles were optimized for maximum solubility using Box-Behnken design using JMP software. The design model was checked for validity by model fit analysis using ANOVA. Solubility for both drugs was increased by about 25 times. Drug release from modified and unmodified nanomicelles was observed to be 12 h. Folic acid transporters/receptors are expressed in ocular tissues. We conjugated folic acid to vitamin E TPGS to target the receptors in order to increase bioavailability. Structure was confirmed by NMR studies. The size of drug loaded targeted micelles was ~12nm. Morphological structure of nanomicelles was analyzed by TEM images. The nanomicelles were uniform and spherical in shape. Cumulative release of 100% was observed for coumarin-6 from targeted nanomicelles within 6 h. No burst release was observed. To confirm the targeting ability of folic acid conjugated nanomicelles, uptake of 3H-folic acid was performed in presence of targeted and non-targeted nanomicelles on Y-79 and D407 cells. Uptake of 3H-folic acid was reduced by 45% and 60% in presence of targeted nanomicelles in Y-79 and D407 cells respectively. To confirm the targeting ability of folic acid conjugated nanomicelles, confocal imaging studies were performed after uptake of coumarin-6 loaded targeted and non-targeted nanomicelles. Confocal images showed increased internalization of folic acid targeted nanomicelles.This research showed that Vitamin E TPGS nanomicelles can be successfully utilized to develop clear aqueous solutions for topical drug delivery of etoposide and fluocinolone acetonide. Folic acid transporter/receptor can be targeted to achieve increased bioavailability.

ISBN: 9781392231906Subjects--Topical Terms:

516420
Chemistry.

Novel Folic Acid Targeted Nanomicelles for Delivery of Hydrophobic Drugs to the Back of the Eye.
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500 $a Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Mitra, Ashim.
502 $a Thesis (Ph.D.)--University of Missouri - Kansas City, 2019.
506 $a This item must not be added to any third party search indexes.
506 $a This item must not be sold to any third party vendors.
520 $a Overall aim of this research project is to develop folic acid targeted nanomicelles loaded with insoluble hydrophobic drugs for delivery to posterior segment of the eye. Retinoblastoma and uveitis are diseases that affect the posterior segment. Etoposide (ET) is used for treatment of retinoblastoma and fluocinolone acetonide (FA) is used for treatment of uveitis. Both drugs have very poor water solubility and it is necessary to develop clear aqueous solutions for topical drug delivery. We utilized vitamin E TPGS polymer to develop nanomicelles to solubilize the drugs. The polymer was also modified with PEG chain having molecular weight of 2000. Synthesis of modified polymer was performed and confirmed by NMR studies. Critical micelle concentration of modified polymer was determined using pyrene method. The size of drug loaded nanomicelles was < 20nm. Nanomicelles were optimized for maximum solubility using Box-Behnken design using JMP software. The design model was checked for validity by model fit analysis using ANOVA. Solubility for both drugs was increased by about 25 times. Drug release from modified and unmodified nanomicelles was observed to be 12 h. Folic acid transporters/receptors are expressed in ocular tissues. We conjugated folic acid to vitamin E TPGS to target the receptors in order to increase bioavailability. Structure was confirmed by NMR studies. The size of drug loaded targeted micelles was ~12nm. Morphological structure of nanomicelles was analyzed by TEM images. The nanomicelles were uniform and spherical in shape. Cumulative release of 100% was observed for coumarin-6 from targeted nanomicelles within 6 h. No burst release was observed. To confirm the targeting ability of folic acid conjugated nanomicelles, uptake of 3H-folic acid was performed in presence of targeted and non-targeted nanomicelles on Y-79 and D407 cells. Uptake of 3H-folic acid was reduced by 45% and 60% in presence of targeted nanomicelles in Y-79 and D407 cells respectively. To confirm the targeting ability of folic acid conjugated nanomicelles, confocal imaging studies were performed after uptake of coumarin-6 loaded targeted and non-targeted nanomicelles. Confocal images showed increased internalization of folic acid targeted nanomicelles.This research showed that Vitamin E TPGS nanomicelles can be successfully utilized to develop clear aqueous solutions for topical drug delivery of etoposide and fluocinolone acetonide. Folic acid transporter/receptor can be targeted to achieve increased bioavailability.
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