Polymer carriers composed of poly(methacrylic acid – grafted – ethylene glycol)
(P(MAA-g-EG)) hydrogels modified with poly(butyl acrylate) (PBA) to form IPNs or
photopolymerized in the presence of poly(methyl methacrylate) (PMMA) nanoparticles
were investigated for their use in the oral delivery of therapeutic agents for cancer
treatment. The P(MAA-g-EG) hydrogel provided pH-responsive and hydrophilic
properties while PBA or PMMA polymers provided hydrophobic properties. An inulin-
doxorubicin conjugate was also synthesized to provide local, direct targeting for the
treatment of colon cancer.
The pH-responsive behavior of these polymer systems was investigated using
equilibrium and dynamic swelling experiments. In gastric conditions (low pH) all
materials were in a collapsed state and in intestinal conditions (neutral pH) these material
were swollen. The equilibrium swelling ratios decreased with increasing hydrophobic
content for both IPNs and compositions of P(MAA-g-EG) containing nanoparticles. The loading efficiencies of doxorubicin, a chemotherapeutic drug, were as high as
56% for IPNs and the IPN structure and hydrophobicity influenced the loading efficiency
values. The loading efficiency of doxorubicin using P(MAA-g-EG) containing
nanoparticles was as high as 64% and increased with increasing weight percent of
PMMA nanoparticles in the P(MAA-g-EG) hydrogel. In gastric conditions (low pH),
IPNs released a majority of the encapsulated doxorubicin (up to 70%) as compared to the
P(MAA-g-EG) containing nanoparticles (up to 27%). P(MAA-g-EG) containing
nanoparticles was used to load and release the inulin-doxorubicin conjugate. Loading
efficiency was 54% and release profiles behaved similarly as doxorubicin.
Both polymer systems were biocompatible with Caco-2, HT29-MTX, and SW620
cell models over concentration ranging from 1 mg/mL to 5 mg/mL and exposure times
lasting from 2 hr to 24 hr. The 75/25 IPN exhibited the highest degree of mucoadhesion
and the P(MAA-g-EG)-5.0NP the lowest. Using the same cell lines and cytotoxicity
assays, the inulin-doxorubicin conjugate was determined to be more toxic than free
doxorubicin at equal doxorubicin concentrations.
Doxorobuicin and inulin-doxorubicin conjugate were tested for transport across
Caco-2/HT29-MTX cell monolayers with and without the presence of unmodified
P(MAA-g-EG) or P(MAA-g-EG)-5.0NP microparticles. The presence of the
microparticles did not increase transport across the cell monolayer which is advantageous
for local, direct delivery to the colon. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/ETD-UT-2012-08-6028 |
| Date | 13 November 2012 |
| Creators | Schoener, Cody Alan |
| Source Sets | University of Texas |
| Language | English |
| Detected Language | English |
| Type | thesis |
| Format | application/pdf |
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