Design of Innovative and Cross-Linker Free Drug Carriers

Bhutani, Utkarsh and Majumdar, Saptarshi (2019) Design of Innovative and Cross-Linker Free Drug Carriers. PhD thesis, Indian institute of technology Hyderabad.

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Abstract

Oral drug delivery has advanced at a brisk pace and has offered many polymeric cargos to have control release of drug molecules. Despite the towering success in this arena, few shortcomings need to be addressed. Critical ones are the lack of material tunability that causes an early degradation, or the high expulsion of drug molecules in the initial hours. To overcome these defects, cross-linkers like glutaraldehyde, have been introduced, however, they add potential toxicity to the system. Alternatives like biodegradable cross-linkers like genipin have a prohibitively high cost. In order to improve these shortcomings, we introduce strategies to design cross-linker free drug delivery vehicles. Sodium alginate and gelatin are the two FDA approved biodegradable polymers used extensively in this research. Throughout the investigation, these polymers were neither cross-linked (few test cases were crosslinked) or chemically functionalized to alter their native state. The goal was to maximize the potential of physical forces (hydrogen bonding and polymer entanglements) in stabilizing these polymers against rapid dissolution. Sodium alginate and gelatin are charged polymers and their association led to the formation of polyelectrolyte hydrogels. The physiochemical properties of these hydrogels were studied in detail. The effect of plasticizers (PEG and glycerol) and monovalent salt (NaCl) was investigated in depth to understand their role in designing an ideal drug carrier. The hydrogels inspired us to investigate the potential of few naturally occurring materials (soya nuggets and cardamom husk) as drug carriers. Soya nuggets are protein-rich and consumed heavily worldwide. Similar to hydrogels it possesses porosity and swells in an aqueous medium. These properties were further scrutinized which led to the transformation of soya nuggets into drug carriers. However, soya nuggets were limited by their low loading efficiency and stability against proteindigesting enzymes. In order to overcome this stumbling block, cardamom husks (naturally occurring Indian spice) were tested. The careful removal of the cardamom seeds led us to a cavity (cardamom husk) that could be used to encapsulate polymerdrug conjugates. Further, the husk was cellulosic, which ensured the stability of the polymeric mixture against the challenging environment of the stomach (acidic, pH ix 1.2) as cellulose-digesting enzymes are absent in humans. The results of this study were favourable as zero order release could be achieved for both hydrophilic (naproxen sodium) and well as hydrophobic (piperine) drug molecules. Finally, the possibility of piperine as a placebo was explored, where piperine was coated over the gelatin capsules to strengthen their stability in the aqueous medium. Piperine hydrophobicity repelled the water molecules from the capsule surface, which enhanced its stability. This stability led to the controlled release of the desired drug i.e. naproxen sodium. The role of hydrogen bonding in forming a piperine layer over these capsules was identified. Molecular modelling studies further elevated the understanding of the crystallization mechanism of piperine on the gelatin surface. Thus, this thesis presents comprehensive strategies to design cross-linker free carriers from naturally derived biopolymers (SA/gelatin hydrogels) as well as from natural biomaterials (soya nuggets and cardamom)

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IITH Creators:
IITH CreatorsORCiD
Majumdar, SaptarshiUNSPECIFIED
Item Type: Thesis (PhD)
Uncontrolled Keywords: controlled release, drug delivery, Hydro-gels, Sodium alginate
Subjects: Chemical Engineering
Divisions: Department of Chemical Engineering
Depositing User: Team Library
Date Deposited: 16 Mar 2019 11:18
Last Modified: 16 Mar 2019 11:18
URI: http://raiith.iith.ac.in/id/eprint/4884
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