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The Resource Novel Folic Acid Targeted Nanomicelles For Delivery Of Hydrophobic Drugs To The Back Of The Eye, by Sujay Shah

Novel Folic Acid Targeted Nanomicelles For Delivery Of Hydrophobic Drugs To The Back Of The Eye, by Sujay Shah

Creator
Author
Contributor
Summary
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
Language
eng
Work
Publication
Extent
1 online resource (142 pages)
Note
  • "A dissertation in Pharmaceutical Sciences and Chemistry."
  • Advisor: Ashim K. Mitra
  • Vita
Contents
  • Literature review
  • Transporters in drug discovery and delivery: a new paradigm in ocular drug design
  • Development and optimization of etoposide loaded nanomicelle aqueous solution
  • Development and optimization of fluocinolone acetonide loaded nanomicelle aqueous solution for the treatment of uveitis
  • Folic acid targeted nanomicelles for drug delivery to posterior segment of the eye
  • Appendix
Instance
Label
Novel Folic Acid Targeted Nanomicelles For Delivery Of Hydrophobic Drugs To The Back Of The Eye
Title
Novel Folic Acid Targeted Nanomicelles For Delivery Of Hydrophobic Drugs To The Back Of The Eye
Statement of responsibility
by Sujay Shah
Creator
Contributor
Author
Degree supervisor
Subject
Genre
Language
eng
Summary
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
Cataloging source
UMK
http://library.link/vocab/creatorDate
1985-
http://library.link/vocab/creatorName
Shah, Sujay
Degree
Ph.D.
Dissertation note
(School of Pharmacy and Department of Chemistry).
Dissertation year
2019.
Granting institution
University of Missouri-Kansas City,
Illustrations
illustrations
Index
no index present
Literary form
non fiction
Nature of contents
  • dictionaries
  • bibliography
  • theses
http://library.link/vocab/relatedWorkOrContributorDate
1954-
http://library.link/vocab/relatedWorkOrContributorName
Mitra, Ashim K.
http://library.link/vocab/subjectName
  • Drug delivery systems
  • Eye
Label
Novel Folic Acid Targeted Nanomicelles For Delivery Of Hydrophobic Drugs To The Back Of The Eye, by Sujay Shah
Instantiates
Publication
Copyright
Note
  • "A dissertation in Pharmaceutical Sciences and Chemistry."
  • Advisor: Ashim K. Mitra
  • Vita
Antecedent source
not applicable
Bibliography note
Includes bibliographical references (pages 134-141)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Color
black and white
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Contents
Literature review -- Transporters in drug discovery and delivery: a new paradigm in ocular drug design -- Development and optimization of etoposide loaded nanomicelle aqueous solution -- Development and optimization of fluocinolone acetonide loaded nanomicelle aqueous solution for the treatment of uveitis -- Folic acid targeted nanomicelles for drug delivery to posterior segment of the eye -- Appendix
Control code
1103442120
Dimensions
unknown
Extent
1 online resource (142 pages)
File format
one file format
Form of item
online
Level of compression
mixed
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations.
Quality assurance targets
not applicable
Specific material designation
remote
System control number
(OCoLC)1103442120
System details
  • The full text of the dissertation is available as an Adobe Acrobat .pdf file; Adobe Acrobat Reader required to view the file
  • Mode of access: World Wide Web
Label
Novel Folic Acid Targeted Nanomicelles For Delivery Of Hydrophobic Drugs To The Back Of The Eye, by Sujay Shah
Publication
Copyright
Note
  • "A dissertation in Pharmaceutical Sciences and Chemistry."
  • Advisor: Ashim K. Mitra
  • Vita
Antecedent source
not applicable
Bibliography note
Includes bibliographical references (pages 134-141)
Carrier category
online resource
Carrier category code
  • cr
Carrier MARC source
rdacarrier
Color
black and white
Content category
text
Content type code
  • txt
Content type MARC source
rdacontent
Contents
Literature review -- Transporters in drug discovery and delivery: a new paradigm in ocular drug design -- Development and optimization of etoposide loaded nanomicelle aqueous solution -- Development and optimization of fluocinolone acetonide loaded nanomicelle aqueous solution for the treatment of uveitis -- Folic acid targeted nanomicelles for drug delivery to posterior segment of the eye -- Appendix
Control code
1103442120
Dimensions
unknown
Extent
1 online resource (142 pages)
File format
one file format
Form of item
online
Level of compression
mixed
Media category
computer
Media MARC source
rdamedia
Media type code
  • c
Other physical details
illustrations.
Quality assurance targets
not applicable
Specific material designation
remote
System control number
(OCoLC)1103442120
System details
  • The full text of the dissertation is available as an Adobe Acrobat .pdf file; Adobe Acrobat Reader required to view the file
  • Mode of access: World Wide Web

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