The Resource Synthesis, Characterization and In-vivo Testing of Photoactivatable Insulin Depots for Continuously Variable and Minimally Invasive Insulin Delivery, by Bhagyesh R. Sarode

Synthesis, Characterization and In-vivo Testing of Photoactivatable Insulin Depots for Continuously Variable and Minimally Invasive Insulin Delivery, by Bhagyesh R. Sarode

Label
Synthesis, Characterization and In-vivo Testing of Photoactivatable Insulin Depots for Continuously Variable and Minimally Invasive Insulin Delivery
Title
Synthesis, Characterization and In-vivo Testing of Photoactivatable Insulin Depots for Continuously Variable and Minimally Invasive Insulin Delivery
Statement of responsibility
by Bhagyesh R. Sarode
Creator
Contributor
Author
Degree supervisor
Subject
Genre
Language
eng
Summary
Proteins are macromolecules involved in a diverse array of functions. Mutations or abnormal levels of proteins are indicated in several diseases. Despite showing early promise, the translation of protein therapeutics into the clinics has been challenging. The stability of these macromolecules, their delivery, and penetration inside the cells have been the main hurdles limiting their true potential. In the dissertation, various strategies to overcome such protein delivery challenges are discussed. Insulin is a lifesaving peptide for millions of diabetics around the world. Despite significant progress in insulin therapies, the quality of life in diabetics is constrained by the burden of multiple daily injections, invasive nature of therapy and inability to control the blood glucose tightly. To address these concerns, we constructed a photoactivatable insulin depot (PAD). In the approach, an insoluble depot of modified insulin was created by linking insulin covalently to photolabile caging moieties. Transcutaneous irradiation breaks the bond to release insulin from the depot into the systemic circulation. Chapter 3 describes the first successful testing on our PAD technology in diabetic animal models. In Chapters 2 and 4, I describe second-generation materials incorporating more efficient photolabile groups utilizing visible light wavelengths and PAD material with greater insulin loading. These changes improved the overall performance by several folds when tested in-vivo. Chapter 5 discusses the strategies addressed to deliver siRNA inside cells for effective light-activated RNA interference (LARI). LARI can be used for studying biology and cellular processes. Once administered, proteins are prone to degradation by ubiquitous proteases, limiting their circulation time and therapeutic effect significantly. Chapter 6 discusses prodrug strategies to temporarily modify proteins to shield them against proteases. We envisioned cross-linking amino acid residues on the surface via small crosslinkers. The tight bridges would hinder proteases from binding to proteins and unwinding the helices preventing their proteolysis. We also attempted integration of this approach to achieve intracellular protein delivery which is another obstacle in protein delivery. Here, the cross linking was performed via disulfide linkages. The disulfide groups would be reduced once inside the cells, yielding native proteins
Cataloging source
UMK
http://library.link/vocab/creatorDate
1990-
http://library.link/vocab/creatorName
Sarode, Bhagyesh R.
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
1966-
http://library.link/vocab/relatedWorkOrContributorName
Friedman, Simon H.
http://library.link/vocab/subjectName
  • Insulin
  • Drug delivery systems
  • Insulin
  • Drug Delivery Systems
Label
Synthesis, Characterization and In-vivo Testing of Photoactivatable Insulin Depots for Continuously Variable and Minimally Invasive Insulin Delivery, by Bhagyesh R. Sarode
Instantiates
Publication
Copyright
Note
  • "A dissertation in Pharmaceutical Sciences and Chemistry."
  • Advisor: Simon H. Friedman
  • Vita
Antecedent source
not applicable
Bibliography note
Includes bibliographical references (pages 275-290)
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
Introduction: photoactivatable insulin depot -- Synthesis of insulin macro polymer -- In-vivo testing of first-generation pad material -- Synthesis and testing of advanced second-generation material -- Light activated SiRNA nanoparticles -- Intracellular protein delivery using protein prodrugs
Control code
1154355096
Dimensions
unknown
Extent
1 online resource (291 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)1154355096
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
Synthesis, Characterization and In-vivo Testing of Photoactivatable Insulin Depots for Continuously Variable and Minimally Invasive Insulin Delivery, by Bhagyesh R. Sarode
Publication
Copyright
Note
  • "A dissertation in Pharmaceutical Sciences and Chemistry."
  • Advisor: Simon H. Friedman
  • Vita
Antecedent source
not applicable
Bibliography note
Includes bibliographical references (pages 275-290)
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
Introduction: photoactivatable insulin depot -- Synthesis of insulin macro polymer -- In-vivo testing of first-generation pad material -- Synthesis and testing of advanced second-generation material -- Light activated SiRNA nanoparticles -- Intracellular protein delivery using protein prodrugs
Control code
1154355096
Dimensions
unknown
Extent
1 online resource (291 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)1154355096
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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