Graduation Year

2020

Document Type

Thesis

Degree

M.S.

Degree Name

Master of Science (M.S.)

Degree Granting Department

Graduate School

Major Professor

Subhra Mohapatra, Ph.D.

Committee Member

Shyam Mohapatra, Ph.D.

Committee Member

Eleni Markoutsa, Ph.D.

Keywords

CRC, CSCs, Hydrogel, Mithramycin-A, Nanotechnology, Nanotherapy

Abstract

Mithramycin-A (Mit-A) is a US Food and Drug Administration (FDA) approved chemotherapeutic agent that is used for the treatment of testicular cancer. According to previous studies, Mit-A has shown promising results in targeting colorectal cancer (CRC) and cancer stem cells (CSCs) which are responsible for a highly invasive and metastatic forms of CRC. The use of Mit-A as chemotherapy is limited in CRC due to its toxicity. To minimize its toxicity, we have developed an orally delivered nanoscale drug delivery system by which Mit-A can be delivered using biocompatible and biodegradable materials. Mit-A nanoparticles were prepared using Poly(lactic-co-glycolic acid) as the inner core and chitosan (CS) on the outer shell of nanoparticles having an average size of 166.66 ± 0.86 nm and were dispersed in alginate/chitosan double crosslinked hydrogel which release the payload at the colonic site to target CRC and CSCs thus, contributing to total cancer therapy. In-vitro and in-vivo results show that oral administration of Mit-A nanoparticles dispersed in hydrogel have a decreased toxicity and can reduce the tumor burden in an orthotopic CRC mouse model. Taken together, an orally administered nanoscale drug delivery system of Mit-A nanoparticles dispersed in the hydrogel is a promising drug delivery system to target CRC and CSCs with reduced toxicity.

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