Mesoporous silica nanomaterials and magnetic nanoparticles based stimuli-responsive controlled-release delivery systems

The research presented and discussed within this dissertation involves the development of mesoporous silica nanomaterials and magnetic nanoparticles based stimuli-responsive controlled-release delivery systems.;A superparamagnetic iron oxide nanoparticle-capped, MCM-41 type mesoporous silica nanorod-based controlled-release delivery system (Magnet-MSN) was synthesized. The stimuli-responsive release profiles of fluorescein-loaded Magnet-MSN delivery systems in the presence of external magnetic field was studied by using cell-produced antioxidants as triggers for releasing fluorescein molecules. The intracellular delivery efficiency of the Magnet-MSN system with human cervical cancer cells (HeLa) in vitro was demonstrated involving fluorescein molecules as model drug.;To take the advantage of the intracellular delivery capability of Magnet-MSN systems, a series of in vitro experiments demonstrating the loading and release of a DNA intercalating drug 9-aminoacridine was performed using Magnet-MSN by the action of reductant triggers. The in vivo application of Magnet-MSN with HeLa cells led to the enhanced cell growth inhibition effect. The cell growth inhibition was found to be unaffected by a strong external magnetic field.;A poly(N-isopropylacrylamide) coated mesoporous silica nanomaterials (PNiPAm-MSN) was demonstrated to load and release drug molecules using thermal stimuli as a trigger. Iron oxide (Fe3O4) nanoparticles were then attached to the surface of drug loaded PNiPAm-MSN to render the system magnetic (Mag-PNiPAm-MSN). Successful release of the loaded drug molecules was shown by placing Mag-PNiPAm-MSN under an alternating current based magnetic field. The mechanism of drug release was explained by the action of hyperthermia effect originating from the attached magnetic nanoparticles under the high frequency alternating magnetic field. The rate of drug release was also shown to be precisely controllable by controlling the parameters of the external magnetic field

Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release

Mesoporous silica nanoparticles (MSNs) are introduced as chemically and thermally stable nanomaterials with well-defined and controllable morphology and porosity. It is shown that these particles possess external and internal surfaces that can be selectively functionalized with multiple organic and inorganic groups. On the basis of these characteristics, the biocompatibility of silica, and their efficient uptake by mammalian cells, MSNs are proposed as the basis of nanodevices for the controlled release of drugs and genes into living cells

Collating and validating indigenous and local knowledge to apply multiple knowledge systems to an environmental challenge: A case-study of pollinators in India

There is an important role for indigenous and local knowledge in a Multiple Evidence Base to make decisions about the use of biodiversity and its management. This is important both to ensure that the knowledge base is complete (comprising both scientific and local knowledge) and to facilitate participation in the decision making process. We present a novel method to gather evidence in which we used a peer-to-peer validation process among farmers that we suggest is analogous to scientific peer review. We used a case-study approach to trial the process focussing on pollinator decline in India. Pollinator decline is a critical challenge for which there is a growing evidence base, however, this is not the case world–wide. In the state of Orissa, India, there are no validated scientific studies that record historical pollinator abundance, therefore local knowledge can contribute substantially and may indeed be the principle component of the available knowledge base. Our aim was to collate and validate local knowledge in preparation for integration with scientific knowledge from other regions, for the purpose of producing a Multiple Evidence Base to develop conservation strategies for pollinators. Farmers reported that vegetable crop yields were declining in many areas of Orissa and that the abundance of important insect crop pollinators has declined sharply across the study area in the last 10–25 years, particularly Apis cerana, Amegilla sp. and Xylocopa sp. Key pollinators for commonly grown crops were identified; both Apris cerana and Xylocopa sp. were ranked highly as pollinators by farmer participants. Crop yield declines were attributed to soil quality, water management, pests, climate change, overuse of chemical inputs and lack of agronomic expertise. Pollinator declines were attributed to the quantity and number of pesticides used. Farmers suggested that fewer pesticides, more natural habitat and the introduction of hives would support pollinator populations. This process of knowledge creation was supported by participants, which led to this paper being co-authored by both scientists and farmers

Mesoporous silica nanomaterials and magnetic nanoparticles based stimuli-responsive controlled-release delivery systems

The research presented and discussed within this dissertation involves the development of mesoporous silica nanomaterials and magnetic nanoparticles based stimuli-responsive controlled-release delivery systems.;A superparamagnetic iron oxide nanoparticle-capped, MCM-41 type mesoporous silica nanorod-based controlled-release delivery system (Magnet-MSN) was synthesized. The stimuli-responsive release profiles of fluorescein-loaded Magnet-MSN delivery systems in the presence of external magnetic field was studied by using cell-produced antioxidants as triggers for releasing fluorescein molecules. The intracellular delivery efficiency of the Magnet-MSN system with human cervical cancer cells (HeLa) in vitro was demonstrated involving fluorescein molecules as model drug.;To take the advantage of the intracellular delivery capability of Magnet-MSN systems, a series of in vitro experiments demonstrating the loading and release of a DNA intercalating drug 9-aminoacridine was performed using Magnet-MSN by the action of reductant triggers. The in vivo application of Magnet-MSN with HeLa cells led to the enhanced cell growth inhibition effect. The cell growth inhibition was found to be unaffected by a strong external magnetic field.;A poly(N-isopropylacrylamide) coated mesoporous silica nanomaterials (PNiPAm-MSN) was demonstrated to load and release drug molecules using thermal stimuli as a trigger. Iron oxide (Fe3O4) nanoparticles were then attached to the surface of drug loaded PNiPAm-MSN to render the system magnetic (Mag-PNiPAm-MSN). Successful release of the loaded drug molecules was shown by placing Mag-PNiPAm-MSN under an alternating current based magnetic field. The mechanism of drug release was explained by the action of hyperthermia effect originating from the attached magnetic nanoparticles under the high frequency alternating magnetic field. The rate of drug release was also shown to be precisely controllable by controlling the parameters of the external magnetic field.</p

Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release

Mesoporous silica nanoparticles (MSNs) are introduced as chemically and thermally stable nanomaterials with well-defined and controllable morphology and porosity. It is shown that these particles possess external and internal surfaces that can be selectively functionalized with multiple organic and inorganic groups. On the basis of these characteristics, the biocompatibility of silica, and their efficient uptake by mammalian cells, MSNs are proposed as the basis of nanodevices for the controlled release of drugs and genes into living cells.Reprinted (adapted) with permission from Accounts of Chemical Research 40 (2007): 846, doi:10.1021/ar600032u. Copyright 2007 American Chemical Society.</p

Behavior of Microstrain in Nd³⁺-Sensitized Near-Infrared Upconverting Core–Shell Nanocrystals for Defect-Induced Tailoring of Luminescence Intensity

In an attempt to optimize the upconversion luminescence (UCL) output of a Nd3+-sensitized near-infrared (808 nm) upconverting core–shell (CS) nanocrystal through deliberate incorporation of lattice defects, a comprehensive analysis of microstrain both at the CS interface and within the core layer was performed using integral breadth calculation of high-energy synchrotron X-ray (λ = 0.568551 Å) diffraction. An atomic level interpretation of such microstrain was performed using pair distribution function analysis of the high-energy total scattering. The core NC developed compressive microstrain, which gradually transformed into tensile microstrain with the growth of the epitaxial shell. Such a reversal was rationalized in terms of a consistent negative lattice mismatch. Upon introduction of lattice defects into the CS systems upon incorporation of Li+, the corresponding UCL intensity was maximized at some specific Li+ incorporation, where the tensile microstrain of CS, compressive microstrain of the core, and atomic level disorders exhibited their respective extreme values irrespective of the activator ions

Alginate Bead Based Hexagonal Close Packed 3D Implant for Bone Tissue Engineering

Success of bone tissue engineering (BTE) relies on the osteogenic microarchitecture of the biopolymeric scaffold and appropriate spatiotemporal distribution of therapeutic molecules (growth factors and drugs) inside it. However, the existing technologies have failed to address both the issues together. Keeping this perspective in mind, we have developed a novel three-dimensional (3D) implant prototype by stacking hexagonal close packed (HCP) layers of calcium alginate beads. The HCP arrangement of the beads lead to a patterned array of interconnected tetrahedral and octahedral pores of average diameter of 142.9 and 262.9 μm, respectively, inside the implant. The swelling pattern of the implants changed from isotropic to anisotropic in the <i>z</i>-direction in the absence of bivalent calcium ions (Ca²⁺) in the swelling buffer. Incubation of the implant in simulated body fluid (SBF) resulted in a 2.7-fold increase in the compressive modulus. The variation in the relaxation times as derived from the Weichert viscoelasticity model predicted a gradual increase in the interactions among the alginate molecules in the matrix. We demonstrated the tunability of the spatiotemporal drug release from the implant in a tissue mimicking porous semisolid matrix as well as in conventional drug release set up by changing the spatial coordinates of the “drug loaded depot layer” inside the implant. The therapeutic potential of the implant was confirmed against <i>Escherichia coli</i> using metronidazole as the model drug. Detailed analysis of cell viability, cell cycle progression, and cytoskeletal reorganization using osteoblast cells (MG-63) proved the osteoconductive nature of the implant. Expression of differentiation markers such as alkaline phosphatase, runx2, and collagen type 1 in human mesenchymal stem cell <i>in vitro</i> confirmed the osteogenic nature of the implant. When tested <i>in vivo</i>, VEGF loaded implant was found capable of inducing angiogenesis in a mice model. In conclusion, the bead based implant may find its utility in non-load-bearing BTE