Development of Chlorambucil Conjugated Folate Receptor Targeted Polyprodrug System for Effective Chemotherapy

Ancy, U (2022) Development of Chlorambucil Conjugated Folate Receptor Targeted Polyprodrug System for Effective Chemotherapy. Masters thesis, theIndian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Ancy U (17MS040)) 17MS040_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

Scientists and engineers have been doing continuous research in developing potent therapeutics for the treatment of cancer, because cancers are one of the most dire diseases present in this century. Because of the stimuli responsiveness of polymer-based systems, it is widely used in the biomedical field, especially in drug delivery for cancer therapy. Herein, a polyprodrug with a norbornene backbone has been designed as a therapeutic system. A chlorambucil drug conjugated monomer, which acts as a DNA alkylating agent. Then a folic acid conjugated monomer for targeting the folate receptors of cancer cells. A tertiary amine with norbornene, for pH responsiveness and a PEG conjugated moiety, acts as the hydrophilic system. Two polymers, CHL-TAMPEG and CHL-TAM-PEG-FOL were synthesized using ring-opening metathesis polymerization (ROMP) technique under the norbornene backbone and can form nano-aggregates because of the amphiphilicity of polymers. Both polymers and monomers formation was confirmed using spectroscopic methods like ¹H NMR, ¹³C NMR, ESI-MS. CHL-TAM-PEG polymer is the non-targeting moiety and CHL-TAM-PEG-FOL polymer is the targeting moiety. Later selfassembly studies have to be done and confirm the morphology studies using DLS/SEM/TEM. Due to the presence of a folic acid segment at the exterior of the nano-aggregates, it would easily can do internalization into the tumor cell through folate receptor mediated endocytosis. The acidic environment of the cancer cells and the esterase enzyme present in it can help in creating a dual stimuli responsive, that causes the disaggregate and hence releases the drug into the cancer cells.

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