The present thesis focuses on the selection of polymers and methods to fabricate stable and stimuli responsive multilayer self-assembly via layer-by-layer (LbL) approach. The polymers utilized in this study are biodegradable and biocompatible such as hyaluronic acid, chitosan
and poly(vinyl alcohol) (PVA). The thesis is comprised of six chapters and a brief discussion on the contents of the individual chapters is given below.
Chapter I reviews the LbL self-assembly approach in the context of drug delivery. The
various interactions such as electrostatic, hydrogen bonding and covalent bonding involved in preparation of stable multilayer assemblies via LbL approach are discussed. Stimuli responsive behaviour of these multilayer assemblies can be tuned by choosing suitable depositing materials and method. Preparation of hollow microcapsules using LbL approach and its application in drug delivery has also been described in this chapter.
Chapter II deals with the LbL assembly of a neutral polymer, poly(vinyl alcholol) (PVA). The negative charge on PVA backbone was induced by physical cross-linking with borax. The PVA-borate can undergo electrostatic interaction with positively charged chitosan in LbL process to form multilayer thin film. The thin film of PVA-borate complex/chitosan was found be responsive towards glucose concentration; disintegration of the multilayer assembly was observed at a high glucose concentration. This finding was rationalized on the basis of strong interaction of glucose with borate ions leading to dissociation of PVA-borate complex
and subsequent collapse of the assembly. Thus, this multilayer self-assembly is potent for glucose triggered drug delivery.
Chapter III reports the construction of a stable hydrogen bonded multilayer self-assembly based on complementary DNA base pairs (adenine and thymine) interaction. The natural polymer such as chitosan was modified with adenine whereas hyaluronic acid was modified with thymine. These two modified polymers were sequentially deposited on flat substrate and
melamine formaldehyde (MF) particles; wherein strong interaction among the DNA base
pairs led to the formation of stable assembly without utilizing any external cross-linking agent. The modified polymers are non-cytotoxic as proved from MTT assay. Further the multilayer assembly was used for pH responsive anticancer drug doxorubicin hydrochloride (DOX) release.
In Chapter IV, glutaraldehyde mediated LbL self-assembly of single polymer multilayer thin films on flat and colloidal substrate by covalent bonding is described. A comparitive study between the native polymer (chitosan) and adenine modified polymer in the growth of thin film is performed. It is established from the study that the conformation of polymer and the availability of cross-linking points on the polymer play a crucial role in controlling the
growth of these multilayer assemblies.
Chapter V is divided into two parts (A and B). Part A describes a simple and unique
protocol for fabrication of water dispersed chitosan nanoparticles (CH NPs). The method
utilized in this work is based on the fast desolvation technique without using any additional stabilizer or any sophisticated instrumental setup. Furthermore, the CH NPs prepared from the mentioned protocol were proved to be cell-viable and are found to be responsive towards pH of the solution. In part B of this chapter, the LbL self-assembly of the responsive CH NPs is fabricated via electrostatic interaction with hyaluronic acid (HA). The growth of the
multilayer thin film was found to be linear as function of number of bilayers. The
morphology of thin film was characterized by atomic force microscopy (AFM) and scanning
electron microscopy (SEM). The microscopic images reveal the uniform film morphology
devoid of any phase separation of nanoparticles and polymers. Subsequently, the film was loaded with an anticancer therapeutic, doxorubicin hydrochloride (DOX). The release dynamics of encapsulated drug from the self-assembly are tunable and pH responsive.
Chapter VI deals with the general and versatile method for the encapsulation of hydrophobic model drugs into polymeric multilayer assembly by using LbL approach. Electrical charge was induced on the surface of pyrene (uncharged organic substance) using an amphiphilic surfactant, sodium dodecyl sulfate (SDS) by micellar solubilization. The SDS micellar solution of pyrene was utilized to grow LbL multilayer thin film on a planar substrate and
colloidal particles along with chitosan as a polycation. The LbL self-assembly of pyrene
loaded SDS micelles/chitosan is additionally able to encapsulate hydrophobic or hydrophilic model therapeutics, thus providing an opportunity for dual-drug delivery. The desorption kinetics of the two model drugs from the thin film is found to follow a second order rate model.
| Identifer | oai:union.ndltd.org:IISc/oai:etd.ncsi.iisc.ernet.in:2005/2020 |
| Date | 05 1900 |
| Creators | Manna, Uttam |
| Contributors | Patil, Satish A |
| Source Sets | India Institute of Science |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | G25012 |
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