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Background
Daniel Carr is originally
from Shreveport, Louisiana. He received
his B.S. in Chemical Engineering from Louisiana
Tech University in 2005. As an undergraduate,
he researched enzyme immobilization via
layer-by-layer self assembly under Dr. Bill
Elmore at Louisiana Tech, and worked on
the development of a vaccine for botulism
under Dr. Ted Randolph at the University
of Colorado at Boulder as part of CU's NSF-REU
program. He is currently pursuing a Ph.D.
in Chemical Engineering at the University
of Texas at Austin under Dr. Peppas as a
National Science Foundation Graduate Research
Fellow.
Research Summary
The oral delivery of proteins is an advantageous
administration route as it alleviates the
associated pain and fear of injection-based
delivery and therefore should increase the
overall patient compliance to adhere to
a prescribed regimen. The low permeabilities
of proteins, degradative environment of
the gastrointestinal tract and the other
physical and chemical barriers to protein
absorption in the small intestine have led
to the development of systems to improve
the protection and release of therapeutic
proteins.
Enteric coatings have been used but solely
provide protection to the drug. Stimuli-sensitive
hydrogels, however, have been shown to provide
many desired features in the delivery of
therapeutic proteins. For the hydrogel system
P(MAA-g-PEG), drug protection, site-specific
release, enzyme inhibition, permeation enhancement
and mucoadhesive capabilities have been
demonstrated. Many strategies are currently
being employed to utilize this system with
modified drugs or specialized tethers to
improve drug delivery, but little work has
been conducted in the area of identifying
improved hydrogel systems.
We propose that a new class of hydrogel
carriers, optimized through the usage of
novel monomeric formulations and control
of system parameters, can promote higher
levels of drug protection from enzymatic
degradation and improved protein release
in the absorptive region of the gastrointestinal
tract. Higher levels of encapsulation and
release should lead to an improvement in
the bioavailability of the therapeutic protein
due to increased concentration gradients
and potential for contact with the intestinal
epithelium. The specific aims of the proposed
research are to:
1. Utilize molecular design and analysis
to optimize the structure of a series of
novel pH-sensitive hydrogel carriers for
application in the oral delivery of proteins
by investigating the effects of monomeric
formulation, crosslinking, and tethered
structures on the overall dynamic behavior.
2. Assess the ability of the optimized carriers
to entrap and protect therapeutic proteins
and to evaluate the in vitro release kinetics
of the systems in physiologically relevant
situations.
3. Investigate the in vitro cytocompatibility
of the carriers and evaluate the effectiveness
of the systems to increase bioavailability
by measuring protein transport across an
intestinal epithelial model.
Publications
D.A. Carr, M.C. Boudes, O.Z.
Fisher and N.A. Peppas, “Growth Hormone
Release from pH-Sensitive Complexation Hydrogels”,
Trans. Soc. Biomat., 32, 249 (2007).
D. Carr and N.A. Peppas, “pH-Sensitive
Complexation Hydrogels for the Oral Delivery
of Proteins”, AAPS PharmSci, W4218 (2006).
Patents
M.C. Boudes, D.A. Carr
and N.A. Peppas, “Formulations and Methods
for Oral Delivery of Proteins”, U.S. patent
(pending).
Presentations
D.A. Carr, M. Gomez-Burgaz,
and N.A. Peppas. “Molecular Design of a
Novel Complexation Hydrogel for the Oral
Delivery of Therapeutic Proteins,” 8th World
Biomaterials Congress. Amsterdam, The Netherlands.
May 28-June 1, 2008 (accepted).
D.A. Carr and N.A. Peppas.
“Complexation Hydrogels of Methacrylic Acid
and N-vinyl Pyrrolidone for the Oral Delivery
of Therapeutic Proteins,” 9th US-Japan Symposium
on Drug Delivery Systems. Lahaina, Maui,
HI. December 16-20, 2007 (accepted).
D.A. Carr, W.A. Hunt and
N.A. Peppas. “Molecular Design and Dynamic
Behavior of Interpolymer Complexing
Hydrogels for the Oral Delivery of
Therapeutic Proteins,” American
Institute of Chemical Engineers Annual
Meeting. Salt Lake City, UT. November 6,
2007.
D.A. Carr, W.A. Hunt and
N.A. Peppas. “Evaluation of Therapeutic
Protein Encapsulation and Release from pH-Sensitive
Complexation Hydrogels,” 16th International
Symposium on Microencapsulation. Lexington,
KY. September 11, 2007.
D.A. Carr, M.C. Boudes,
O.Z. Fisher and N.A. Peppas. “Growth Hormone
Release from pH-Sensitive Complexation Hydrogels,”
Society for Biomaterials Annual Meeting.
Chicago, IL. April 21, 2007.
D.A. Carr and N.A. Peppas.
“Molecular Analysis of Interpolymer Complexing
Hydrogels Based on Poly(Methacrylic Acid)
and N-Vinyl Pyrrolidone as Carriers for
Protein Delivery,” Graduate and Industry
Networking (GAIN) Conference, The University
of Texas at Austin. Austin, TX. February
21, 2007.
D.A. Carr, M.C. Boudes,
O.Z. Fisher and N.A. Peppas. “Growth Hormone
Release Using pH-Sensitive Complexation
Hydrogels,” The Houston Society for Engineering
in Medicine and Biology Conference on Biomedical
Engineering Research. Houston, TX. February
8, 2007.
D.A. Carr and N.A. Peppas.
“Molecular Analysis of Interpolymer Complexing
Hydrogels Based on Poly(Methacrylic Acid)
and N-Vinyl Pyrrolidone as Carriers for
Protein Delivery by Transmucosal Transport,”
American Institute of Chemical Engineers
Annual Meeting. San Francisco, CA. November
14, 2006.
D.A. Carr, M.C. Boudes,
O.Z. Fisher, and N.A. Peppas. “pH-Sensitive
Complexation Hydrogels for the Oral Delivery
of Proteins,” American Association of Pharmaceutical
Scientists Annual Meeting and Exposition.
San Antonio, TX. November, 1, 2006.
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