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Medicinal and Pharmaceutical Chemistry

Theses & Dissertations

Theses/Dissertations

2020

Polymer-drug conjugate

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Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash May 2020

Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash

Theses & Dissertations

Purpose The aim of this study was to determine whether coadministration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonategraft- dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice.

Methods P-DTX and P-CYP were synthesized from mPEGb- PCC through carbodiimide coupling reaction and characterized by 1H–NMR. The micelles were prepared by film hydration and particle size was measured by dynamic light scattering (DLS). Cytotoxicity, apoptosis and cell cycle analysis of P-DTX and P-CYP were evaluated in MIA PaCa-2 cells. In vivo efficacy …