Vijay T. John

Curcumin-loaded γ-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma

UNLABELLED The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumins potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-γ-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded γ-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin. FROM THE CLINICAL EDITOR Curcumin-loaded γ-cyclodextrin liposomes were demonstrated in vitro to have significant potential as delivery vehicles for the treatment of cancers of mesenchymal and epithelial origin. Differences between mechanisms of cell death were also evaluated.

Surfactant-laden soft contact lenses for extended delivery of ophthalmic drugs.

Eye drops are inefficient means of delivering ophthalmic drugs because of limited bioavailability and these can cause significant side effects due to systemic uptake of the drug. The bioavailability for ophthalmic drugs can be increased significantly by using contact lenses. This study focuses on the development of surfactant-laden poly-hydroxy ethyl methacrylate (p-HEMA) contact lenses that can release Cyclosporine A (CyA) at a controlled rate for extended periods of time. We focus on various Brij surfactants to investigate the effects of chain length and the presence of an unsaturated group on the drug release dynamics and partitioning inside the surfactant domains inside the gel. The gels were imaged by cryogenic scanning electron microscopy (cryo-SEM) to obtain direct evidence of the presence of surfactant aggregates in the gel, and to investigate the detailed microstructure for different surfactants. The images show a distribution of nano pores inside the surfactant-laden hydrogels which we speculate are regions of surfactant aggregates, possibly vesicles that have a high affinity for the hydrophobic drug molecule. The gels are further characterized by studying their mechanical and physical properties such as transparency, surface contact angle and equilibrium water content to determine their suitability as extended wear contact lenses. Results show that Brij surfactant-laden p-HEMA gels provide extended release of CyA, and possess suitable mechanical and optical properties for contact lens applications. The gels are not as effective for extended release of two other hydrophobic ophthalmic drugs, dexamethasone (DMS) and dexamethasone 21 acetate (DMSA) because of insufficient partitioning inside the surfactant aggregates.

Magnetic properties of a series of ferrite nanoparticles synthesized in reverse micelles

Nanoscale particles of the general formula MFe/sub 2/O/sub 4/ (M=Co, Mn, Fe) were synthesized in reverse micelles of twin-tailed anionic bis(2-ethylhexyl) sodium sulfosuccinate (AOT) in isooctane. The size of the particles was controlled by adjusting the AOT/water molar ratio. Particle sizes were confirmed using XRD and uniformity was determined by SEM. Magnetic measurements, carried out using a SQUID Susceptometer, indicated superparamagnetic behavior. FC and ZFC demagnetization experiments indicate blocking temperatures of 46 K, 30 K, and 7 K for for MFe/sub 2/O/sub 4/ M=Co, Mn, Fe respectively. Below blocking temperatures, the nanoparticles demonstrate hysteresis with coercivities of H/sub c/=6000G, 3800G, and 500G for the Co, Mn, and Fe ferrites.

Recent developments in materials synthesis in surfactant systems

The paper reviews the use of surfactant self-assembly to template the synthesis of polymers, ceramics with extended structures, and nanoparticles. The objective of the review is to highlight newer concepts linking self-assembly to materials nanostructure and to the realization of functional materials.

Superparamagnetic Iron Oxide Nanoparticles with Variable Size and an Iron Oxidation State as Prospective Imaging Agents

Magnetite nanoparticles in the size range of 3.2-7.5 nm were synthesized in high yields under variable reaction conditions using high-temperature hydrolysis of the precursor iron(II) and iron(III) alkoxides in diethylene glycol solution. The average sizes of the particles were adjusted by changing the reaction temperature and time and by using a sequential growth technique. To obtain γ-iron(III) oxide particles in the same range of sizes, magnetite particles were oxidized with dry oxygen in diethylene glycol at room temperature. The products were characterized by DLS, TEM, X-ray powder diffractometry, TGA, chemical analysis, and magnetic measurements. NMR r(1) and r(2) relaxivity measurements in water and diethylene glycol (for OH and CH(2) protons) have shown a decrease in the r(2)/r(1) ratio with the particle size reduction, which correlates with the results of magnetic measurements on magnetite nanoparticles. Saturation magnetization of the oxidized particles was found to be 20% lower than that for Fe(3)O(4) with the same particle size, but their r(1) relaxivities are similar. Because the oxidation of magnetite is spontaneous under ambient conditions, it was important to learn that the oxidation product has no disadvantages as compared to its precursor and therefore may be a better prospective imaging agent because of its chemical stability.

Multifunctional Iron−Carbon Nanocomposites through an Aerosol-Based Process for the In Situ Remediation of Chlorinated Hydrocarbons

Spherical iron-carbon nanocomposites were developed through a facile aerosol-based process with sucrose and iron chloride as starting materials. These composites exhibit multiple functionalities relevant to the in situ remediation of chlorinated hydrocarbons such as trichloroethylene (TCE). The distribution and immobilization of iron nanoparticles on the surface of carbon spheres prevents zerovalent nanoiron aggregation with maintenance of reactivity. The aerosol-based carbon microspheres allow adsorption of TCE, thus removing dissolved TCE rapidly and facilitating reaction by increasing the local concentration of TCE in the vicinity of iron nanoparticles. The strongly adsorptive property of the composites may also prevent release of any toxic chlorinated intermediate products. The composite particles are in the optimal range for transport through groundwater saturated sediments. Furthermore, those iron-carbon composites can be designed at low cost, the process is amenable to scale-up for in situ application, and the materials are intrinsically benign to the environment.

Fluorescence quenching of CdS nanocrystallites in AOT water-in-oil microemulsions

Abstract The luminescence of CdS nanoparticles suspended in “dry” AOT reversed micelles is quite intense but is quenched by water and even more effectively by thiol-containing compounds. Stern-Volmer plots provide information about the quenching efficiencies of various compounds. Of particular interest is 4-hydroxythiophenol which interacts strongly with the surfactant headgroups and thereby partitions to the nanoparticle surface. The quenching efficiency of 4-hydroxythiophenol is more than an order of magnitude greater than that of thiophenol. At the very low concentrations of 4-hydroxythiophenol required to bring about quenching, a remarkable recovery of fluorescence is observed upon continued irradiation. The fluorescence recovery is attributed to photochemical oxidation which consumes the hydroxythiophenol presumably giving a disulfide product.

Attachment of a hydrophobically modified biopolymer at the oil-water interface in the treatment of oil spills.

The stability of crude oil droplets formed by adding chemical dispersants can be considerably enhanced by the use of the biopolymer, hydrophobically modified chitosan. Turbidimetric analyses show that emulsions of crude oil in saline water prepared using a combination of the biopolymer and the well-studied chemical dispersant (Corexit 9500A) remain stable for extended periods in comparison to emulsions stabilized by the dispersant alone. We hypothesize that the hydrophobic residues from the polymer preferentially anchor in the oil droplets, thereby forming a layer of the polymer around the droplets. The enhanced stability of the droplets is due to the polymer layer providing an increase in electrostatic and steric repulsions and thereby a large barrier to droplet coalescence. Our results show that the addition of hydrophobically modified chitosan following the application of chemical dispersant to an oil spill can potentially reduce the use of chemical dispersants. Increasing the molecular weight of the biopolymer changes the rheological properties of the oil-in-water emulsion to that of a weak gel. The ability of the biopolymer to tether the oil droplets in a gel-like matrix has potential applications in the immobilization of surface oil spills for enhanced removal.

Hydration Effects on Skin Microstructure as Probed by High-Resolution Cryo-Scanning Electron Microscopy and Mechanistic Implications to Enhanced Transcutaneous Delivery of Biomacromolecules

Although hydration is long known to improve the permeability of skin, penetration of macromolecules such as proteins is limited and the understanding of enhanced transport is based on empirical observations. This study uses high-resolution cryo-scanning electron microscopy to visualize microstructural changes in the stratum corneum (SC) and enable a mechanistic interpretation of biomacromolecule penetration through highly hydrated porcine skin. Swollen corneocytes, separation of lipid bilayers in the SC intercellular space to form cisternae, and networks of spherical particulates are observed in porcine skin tissue hydrated for a period of 4-10 h. This is explained through compaction of skin lipids when hydrated, a reversal in the conformational transition from unilamellar liposomes in lamellar granules to lamellae between keratinocytes when the SC skin barrier is initially established. Confocal microscopy studies show distinct enhancement in penetration of fluorescein isothiocyanate-bovine serum albumin (FITC-BSA) through skin hydrated for 4-10 h, and limited penetration of FITC-BSA once skin is restored to its natively hydrated structure when exposed to the environment for 2-3 h. These results demonstrate the effectiveness of a 4-10 h hydration period to enhance transcutaneous penetration of large biomacromolecules without permanently damaging the skin.

Cobalt-ferrite nanoparticles: Structure, cation distributions, and magnetic properties

Cobalt–ferrite nanoparticles have been synthesized in water-in-oil microemulsions (reversed micelles) with varying cation composition. The microenvironment provides a template effect that controls the size and particle shape. Transmission electron microscopy reveals that the particles are nanospheres with particle size ranging from 12 to 18 nm. X-ray diffraction results indicate that at low Co2+:Fe2+ ratio (1:10 and 1:5) in the precursor, the particles retain an essentially ferrite structure (γ-Fe2O3). However, the cobalt–ferrite phase (CoFe2O4) forms upon further increase of the Co2+ content. The materials are found to exhibit superparamagnetism. The blocking temperatures and coercivities are dependent on the Co2+:Fe2+ ratio in the system.