Deeptangshu Chaudhary

Doxorubicin‐Conjugated Mesoporous Magnetic Colloidal Nanocrystal Clusters Stabilized by Polysaccharide as a Smart Anticancer Drug Vehicle

Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (-CONHNH(2)). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 4-5 in the late stage of endolysosome and pH 5-6 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release.

Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles

Hierarchical structured nanomaterials with diverse functionality, such as magnetic susceptibility, stimuli-responsiveness, environmental sensing and biocompatibility, are highly sought after for biomedicine and biodetection alike. In this study, we designed and fabricated a new kind of multifunctional core/shell nanospheres as biodegradable targeted drug carriers, the controlled drug release progress and therapeutic effect were monitored in-situ by the fluorescent state of the cells. Firstly, the core/shell nanospheres with biodegradability were synthesized using magnetic supraparticles (MSPs) as core and the layered double hydroxide (LDH) as shell via a hydrothermal route, the reaction parameters were well investigated to obtain the desired structure of the LDH shell. The anti-cancer drug doxorubicin was modified with carboxyl group (DOX-COOH) and loaded in the shell of MSPs/LDH nanospheres via an anion-exchange intercalation. To endow the nanospheres with tumor-targeting capability, IDA (iminodiacetic acid)-modified folate was successfully immobilized onto the surface of LDH shell using chelating interaction. These nanospheres behaved as multifunctional carriers for targeted delivery of anti-cancer drug, doxorubicin (DOX), within Hela cells and thus, these nano-drugs exhibited clear cytotoxicity and inhibition toward Hela cells as compared to normal cell-lines of HEK 293T cells. Interestingly, after the internalization of these nano-drugs, there was a sharp contrast in illumination between the tumorous Hela cells and the normal HEK 293T cells, the acidic cytoplasm of Hela cell stimulated DOX-COOH in LDH shell quickly degraded into positive-charged DOX, and then rapidly escaped from the positive-charged intercalation of LDH shell by strong repulsive interaction, the released DOX rapidly lit up the whole tumor cells in a short time, but only very weak light was found in HEK 293T cells.

Effect of plasticizers on the moisture migration behavior of low-amylose starch films during drying

We report the synergistic and competitive interactions between multiple plasticizers in plasticized low-amylose starch that result in either enhanced or reduced water migration fluxes and effective moisture diffusivities. The starch was plasticized using glycerol and xylitol either individually or in 1:1 combination. The water migration fluxes and moisture diffusivities were higher in xylitol plasticized films compared to the glycerol plasticized ones. For low plasticizer concentrations, the presence of both the plasticizers competitively reduced the effective moisture diffusivities and moisture migration fluxes due to antiplasticization. However, at higher plasticizer contents (at and above 15 wt%), the presence of multiple plasticizers enhanced the moisture migration fluxes and effective moisture diffusivities due to synergistic plasticization. The moisture migration fluxes and effective moisture diffusivities exhibited both moisture and plasticizer concentration dependence and the former was found to be stronger than the latter. These findings can be used for designing and controlling the vapor barrier properties of starch-based bioplastics during drying and formulation phase.

Morphological Investigation into Starch Bio-Nanocomposites via Synchrotron Radiation and Differential Scanning Calorimetry

We studied a hydrophilic, plasticized bionanocomposite system involving sorbitol plasticizer, amylose biopolymer, and montmorillonite (MMT) for the presence of competitive interactions among them at different moisture content. Synchrotron analysis via small angle X-ray scattering (SAXS) and thermal analysis using differential scanning calorimetry (DSC) were performed to understand crystalline growth and the distribution of crystalline domains within the samples. The SAXS diffraction patterns showed reduced interhelix spacing in the amylose network indicating strong amylose-sorbitol interactions. Depending on the sorbitol and MMT concentration, these interactions also affected the free moisture content and crystalline domains. Domains of around 95 A and 312 A were found in the low-moisture-content samples as compared to a single domain of 95 A in the high-moisture-content samples. DSC measurements confirmed that the MMT increased the onset and the melting temperature of nanocomposites. Moreover, the results showed that the ternary interactions among sorbitol-amylose-MMT supported the crystalline heterogeneity through secondary nucleation.

The Moisture Migration Behavior of Plasticized Starch Biopolymer

Using plasticized starch pellets as a precursor for making thermoformed products is a commercially viable and profitable idea. However, drying of plasticized starch is quite complex in nature, partly due to the synergistic interactions between starch and plasticizers in the presence of water. The migration of water from starch pellets plasticized by two components, glycerol and xylitol, at three different temperatures was investigated in the present work. Evidence for synergistic interaction between plasticizers and water within starch is shown by the reduced effective moisture diffusivities and moisture migration fluxes at different overall plasticizer concentrations. In addition, the effective moisture diffusivities showed stronger dependence on moisture concentration and the plasticizer molecular weight even though the moisture flux was comparable. The drying process was characterized by two effective diffusion coefficients (D 1, D 2) and, interestingly, the coefficients were an order of significance apart. The Peleg model was investigated for predicting the drying behavior and it is shown that the Peleg constants k 1 and k 2 increase with temperature. k 2, Which is related to material structure and morphology, showed comparable modification by addition of plasticizers, indicating that plasticizers were able to modify the fundamental structure, and xylitol showed greater average k 2 values than glycerol. Further, because k 1 is related with moisture diffusivity, the effect of temperature on diffusivity was interpreted using the Arrhenius relationship. The activation energy values confirm that plasticizers can lock in water within the new structure. Overall, the larger structure of xylitol showed better stability in controlling moisture diffusivities and migration fluxes. These findings can provide better insights in designing and controlling the vapor barrier properties of starch-based packaging materials.

Ultrasonic treatment and synthesis of sugar alcohol modified Na+-montmorillonite clay

Na(+)-montmorillonite clay (generally referred to as MMT) is very useful for reinforcing polymeric matrix at very low concentrations (typically, 2-5% wt). These clay particles are typically exfoliated before they can demonstrate the significant gains in heat deflection temperature, modulus, and elongation properties. In the case of hydrophilic biopolymer based matrices, such as carbohydrates and chitosan, exfoliating these nanoclay particles needs greater attention because the exfoliation is typically carried out using hydrophobic oligomers through ion-exchange. This study reports a new method of synthesizing completely hydrophilic MMT-assemblages using hydrophilic plasticizers for biopolymers. We used sugar alcohols (glycerol, xylitol with 3 and 5 hydroxyl groups) and polysaccharide maltodextrin to exfoliate the MMT. Sonication was conducted for MMT nanoclay and plasticizers at different weight ratios. It was confirmed that all plasticizer/modifier led to expansion of MMT gallery spacing (d-spacing) and the change in d-spacing could be related to the molecular structure of the plasticizer. Meanwhile, the extent of exfoliation was maximum with maltodextrin (fully exfoliation with 1:10 and 1:20 ratio of MMT:plasticizer) across all test samples and interestingly, glycerol and xylitol samples quickly established within the MMT galleries and exhibited minimal influence with further increase in relative concentrations.

Phase behaviour of gelatin/polydextrose mixtures at high levels of solids

This investigation focuses on understanding the phase behaviour of gelatin when mixed with polydextrose (co-solute) primarily at high solid concentrations. The experimental work was carried out using small deformation dynamic oscillation in shear, modulated differential scanning calorimetry, Fourier transform infrared spectroscopy, wide angle X-ray diffraction and environmental scanning electron microscopy. A progression in the mechanical strength and thermal stability of the gelatin network was observed with the addition of polydextrose to the system. Combined thermomechanical and microscopy evidence argues for the development of phase separation phenomenon between protein and co-solute in high-solid preparations, where gelatin maintains helical conformation to provide network integrity as well as glassy consistency at subzero temperature. At the high solids regime, glassy consistency was treated with theoretical frameworks from the synthetic polymer research to pinpoint the glass transition temperature of the system.

Investigation on the phase behaviour of gelatin/agarose mixture in an environment of reduced solvent quality

Investigation on the phase behaviour of a biopolymer mixture has been performed using 7.5% (w/w) gelatin and 1.5% (w/w) agarose in the presence of variable amounts of polydextrose as the co-solute from low to high levels of total solids. Mechanical observation of the system was performed using small deformation dynamic oscillation in shear along with thermal studies using modulated differential scanning calorimetry. Micrographs provided images of the changing morphology of the network with the addition of co-solute. Agarose and gelatin form non-interactive bicontinuous phases in the aqueous environment. Systematic increase in the concentration of polydextrose prevents the formation of a stable agarose network, with the polysaccharide chains dispersing in the high solids environment. Gelatin, on the other hand, retains its conformational stability even at a saturating co-solute environment through enhanced protein structuring. Vitrification studies on the high solids system at subzero temperatures provides information on the structural and molecular relaxation identified as a glass transition phenomenon. Fourier transform infrared spectroscopy was used to analyse potential direct interaction between polymers and co-solute. The extent of amorphicity in the system was confirmed using wide angle X-ray diffraction.

Analysis on the effectiveness of co-solute on the network integrity of high methoxy pectin

Co-solute requirements for high methoxy pectin gelation were observed by the addition of glucose syrup and polydextrose at concentrations varying from 50% to 78% (w/w). Pectin content was fixed at 2% (w/w) in formulations. Studies from small deformation dynamic oscillation in shear, modulated differential scanning calorimetry and environmental scanning electron microscopy are reported. Structural properties of pectin preparations were recorded in relation to the molecular weight and concentration of added co-solute in an acidic environment (pH ∼3.0). High levels of co-solute induce formation of weak pectin gels at elevated temperatures (even at 95°C), which upon subsequent cooling exhibit increasing strength and convert to a clear glass at subzero temperatures. Fourier Transform Infrared Spectroscopy and wide angle X-ray diffraction were practised to examine the nature of interactions between polymer and co-solute and the extent of amorphicity of preparations. Glucose syrup is an efficient plasticiser leading to a reduction in the glass transition temperature (T(g)) of the pectin network, whereas polydextrose assists in the formation of stronger pectin gels in the rubbery state.

Effect of Cultivars and Thermal Processing with Salt Solutions on the Textural Attributes (Hardness, Chewiness and Rate of Softening) of Potatoes (Solanum Tuberosum L.)

The change in textural attributes (hardness, chewiness and rate of softening) of three potato cultivars (Russet Burbank, Desiree and Sebago) was investigated. Uniform cylindrical samples (35-mm diameter and 3-mm thick) were prepared and exposed to different thermal processing regimes including; heating at 85°C, 95°C in water and steaming (100.2°C). The effect of salt on these textural attributes was also investigated using different salt concentrations (1.5%, 3% and 6% (w/w) NaCl). After thermal treatments the samples were subjected to texture profile analysis. The instrumental textural attributes were greatly affected by the cultivars and the thermal processing regimes. The change in textural attributes upon steaming was only marginally different compared to that at 95°C in water. Low concentrations of salt (1–3%) were found to accelerate the softening of the texture in these cultivars especially at lower temperatures. The textural attributes were modelled using a two-parameter reaction kinetics model. There was reasonable agreement by the model findings on the textural attributes prepared from all the thermal processing regimes and in presence and absence of (within average absolute error of 1.9–7%). Further, the model indicated that the order of reaction varied from 1.15–2.18 indicating that the changes in textural attributes in these thermal processing regimes followed higher reaction orders.