Please use this identifier to cite or link to this item: http://hdl.handle.net/10603/251990
Title: Tumor Targeted Multifunctional Poly amidoamine PAMAM Dendrimers to Promote Delivery of Poorly Soluble Chemotherapeutic Agent Paclitaxel in Cancer
Researcher: ROMPICHARLA S V KIRAN
Guide(s): SWATI BISWAS
Keywords: Clinical Pre Clinical and Health,Pharmacology and Toxicology,Substance Abuse drugs
Dendrimers, Chemotherapeutic
University: Birla Institute of Technology and Science
Completed Date: 2018
Abstract: Dendrimers have gained much attention in the recent years for their unique architecture and feasibility of surface modification to cater various functions in drug delivery. They have been successfully explored for delivery of poorly soluble anti-cancer molecules to different types of cancers. The purpose of the present research is to study the delivery potential of dendrimers in targeting anti-cancer agents specifically to tumors by utilizing various benefits they offer in improving the biopharmaceutical properties of the drugs. The current thesis focuses on the delivery of paclitaxel (PTX), a poorly soluble chemotherapeutic agent to cancer cells utilizing poly(amidoamine) (PAMAM) dendrimers as delivery system. Initially, PTX was covalently attached to the generation 4.0 PAMAM dendrimer via a succinate linker using acid/amine coupling reaction to yield G4-PTX. Polyethylene glycol has been conjugated to the amine terminals of the G4 PAMAM dendrimer-PTX conjugate to improve the distribution and decrease the toxicity of cationic dendrimers. In the first part of the study, G4-PTX-PEG was anchored with octa-arginine (R8), a cell penetrating peptide to improve the penetration of conjugate into the cells. The synthesized dendrimers were characterized by proton NMR, gel permeation chromatography (GPC), and zeta potential measurements to confirm the formation of conjugates. From the GPC analysis, it was observed that approximately 2.5 molecules of PTX, 10.5 molecules of PEG and 1.8 molecules of R8 were attached to each G4 PAMAM dendrimer molecule. Hemolytic toxicity of the dendrimer conjugates revealed that PEGylated dendrimers were non-toxic to the cells and R8 modification did not cause any toxicity. The synthesized constructs were evaluated in human cervical cancer cells (HeLa) as monolayers as well as 3D multicellular spheroids. The R8 tagged newlineconjugate was found to internalize efficiently into the cancer cells as assessed by microscopy and flow cytometry. The cytotoxic potential of PTX was significantly improved upon
Pagination: 157
URI: http://hdl.handle.net/10603/251990
Appears in Departments:Pharmacy

Files in This Item:
File Description SizeFormat 
2014phxf0010h_thesis.pdfAttached File8.3 MBAdobe PDFView/Open


Items in Shodhganga are protected by copyright, with all rights reserved, unless otherwise indicated.

Altmetric Badge: