Development of Polymeric nanocarriers for Drug Delivery to Cancer Cells
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2009
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Abstract
Designing of nanosystems that are able to deliver therapeutic molecules to the right place, at a desired dose, at the appropriate time in a controlled manner is currently an important area of research. Pharmaceutical nanocarriers have evolved as one of the major means for drug delivery in cancer chemotherapy due to their unique advantages over conventional dosage. The present research work deals with the development of polymeric nanocarriers for delivery of curcumin, a potential anticancer molecule. Curcumin has showed great promises in the last decade for cancer therapy but the clinical progress of this compound has been slow due to its poor water solubility and low bioavailability. Nanocarrier based delivery of curcumin could provide an opportunity to expand the clinical repertoire of this efficacious agent by enabling aqueous dispersion. Based on these considerations, the objectives of the present research work were fixed as follows: 1. Development of a synthetic nanocarrier and its application in curcumin delivery. i. Synthesis and characterization of synthetic mPEG-PA nanocarrier. ii. Evaluation of the nanocarrier for drug encapsulation. iii. Delivery of the nanocarrier encapsulated drug to in vitro cultured cancer cells. 2. Formulation of curcumin in Pluronic nanocarriers. i. Encapsulation of curcumin in Pluronic nanocarriers by self assembly. ii. Study of drug release and stability of the Pluronic based formulations. iii. Delivery of Pluronic encapsulated curcumin to in vitro cultured cancer cells. 3. Natural food protein based nanoparticle for curcumin delivery. i. Purification and characterization of casein micellar nanoparticles from milk. ii. Fluorescence study of curcumin binding to casein micelle nanoparticles. iii. Effect of curcumin complexed casein micelles on in vitro cultured cancer cells. Chapter One starts with a brief historical development of the concept of drug delivery and moves onto describe the fundamental understanding of drug delivery systems with an emphasis on nanosystems. A review of different types of nanocarriers used in drug delivery and their advantages has been discussed with a focus on cancer therapy. Detailed discussions on the use of inorganic, lipid and polymer based nanocarrier systems are presented along with information about the various commercialized drug delivery products based on nanosystems. The chapter also discusses about the chemistry and multi-therapeutic potential of curcumin. The clinical progress of curcumin, recent advances in the area of its delivery and its promising future as a chemotherapeutic drug against cancer are also reviewed. Chapter Two describes the synthesis of a novel synthetic nanocarrier for curcumin delivery. An amphiphilic polymer, mPEG-PA was synthesized by conjugating mPEG with palmitate by an ester linkage in a single step reaction. The conjugate forms micelle based nanocarriers by self-assembly in aqueous solution. mPEG-PA was characterized through 1HNMR and FT-IR spectroscopy. The size and morphology of the micelle nanostructures were characterized by DLS and AFM. The mPEG-PA based micelle nanocarriers were able to encapsulate curcumin in its hydrophobic core and also efficiently delivers it to the cancer cells. Chapter Three deals with use of Pluronics for curcumin delivery. Pluronics are commercially available FDA approved tri-block copolymers for pharmaceutical appl...
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Supervisor: Utpal Bora and Pranab Goswami
Keywords
BIOSCIENCES AND BIOENGINEERING