- Title Information
- Title
- Engineering Double-Walled Nanospheres for More Effective Oral Drug Delivery: Quantitative Analysis of Uptake, Biodistribution, Bioadhesion and Nanoencapsulation
- Name:
Personal
- Name Part
- Cho, Daniel Y
- Role
- Role Term:
Text
- creator
- Origin Information
- Copyright Date
- 2012
- Physical Description
- Extent
- xxi, 219 p.
- digitalOrigin
- born digital
- Note
- Thesis (Ph.D. -- Brown University (2012)
- Name:
Personal
- Name Part
- Mathiowitz, Edith
- Role
- Role Term:
Text
- Director
- Name:
Personal
- Name Part
- Morgan, Jeffrey
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Darling, Eric
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Palmore, G. Tayhas
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Zielinski, Beth
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. BIOMED: Artificial Organs, Biomaterials, and Cell Technology
- Role
- Role Term:
Text
- sponsor
- Genre (aat)
- theses
- Abstract
- The field of medicine relies heavily on the use of therapeutic agents for the treatment of various illnesses but many of these drugs have chemical or physical properties that prevent them from being administered orally, despite this being the most convenient method with the highest rates of patient comfort and compliance. The use of polymeric microspheres and nanospheres shows significant promise due to their ability to protect the drug from the harsh GI environment while allowing for controlled drug release kinetics. The ultimate goal of this work is to provide a foundation for the development of more effective oral drug delivery platforms based on the knowledge obtained from systematic evaluations of particle uptake mechanisms, bioadhesion, nanosphere preparation and protein encapsulation. In vivo studies revealed an inverse relationship between particle size and uptake from the small intestine while implicating endocytotic mechanisms by enterocytes as the predominant pathway of particle internalization. A series of bioinspired bioadhesive polymers capable of generating and sustaining strong bioadhesive interactions with the small intestinal mucosa were developed and used to engineer bioadhesive and biodegradable double-walled nanospheres via a sequential phase inversion nanoencapsulation method for use as carriers in oral drug delivery. Evaluation of these nanospheres in vivo revealed an 11.5-fold enhancement of particle uptake through the incorporation of a bioadhesive polymer shell to non-adhesive nanospheres suggesting that bioadhesion is an effective strategy for achieving efficient uptake of orally administered particulate drug carriers. Additionally, the systematic evaluation of protein encapsulation by phase inversion revealed that high actual drug loadings, reduced initial burst release and sustained release kinetics can be achieved over a 42 day period to deliver physiologically relevant levels of insulin from 500 nm poly(lactic-co-glycolic acid) nanospheres. Through the systematic evaluation of particle uptake and tissue distribution, the synthesis and characterization of novel bioadhesive polymers, the development of novel nanoencapsulation methods and systematic evaluation of protein nanoencapsulation by phase inversion, we have provided a framework upon which to develop more effective oral drug delivery platforms.
- Subject
- Topic
- drug delivery
- Subject
- Topic
- polymer science
- Subject
- Topic
- nanoencapsulation
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/898667")
- Topic
- Drug delivery systems
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20121023
- Language
- Language Term:
Code (ISO639-2B)
- eng
- Language Term:
Text
- English
- Identifier:
DOI
- 10.7301/Z06971WR
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.
- Type of Resource (primo)
- dissertations