Alina M. Alb

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.

Online Monitoring of Chain Transfer in Free-Radical Polymerization

A recently introduced, automated method for online monitoring of polymerization reactions was used to study free-radical transfer reactions. The persulfate initiated polymerization of acrylamide (AAm) in water was chosen as the test system. Chain transfer properties of ethanol (EyOH) and propanol (PrOH) were investigated. Different methods of computing the transfer constant are compared, including those based on the slope and intercept behavior of the monitored cumulative weight-average molecular mass as a function of conversion, M w (f), the reduced viscosity, and corresponding size exclusion chromatography analysis of the reaction end products. To a close approximation, the chain transfer agents were found to obey the form expected when ideal free-radical polymerization takes place and radical transfer from propagating radicals to the chain transfer agent (CTA) is slower than from the CTA to monomer, that is, the polymer molar mass decreases with increasing chain transfer agent, but there is no appreciable effect on the kinetics of monomer conversion. The AAm kinetics were characterized in terms of the ratio κ 2 p /κ t , where κ p and κ t are the propagation and termination rate constants, respectively.

Efficient Synthesis of High Purity Homo-arm and Mikto-arm Poly(ethylene glycol) Stars Using Epoxide and Azide–Alkyne Coupling Chemistry

High purity homo-arm and mikto-arm poly(ethylene glycol) (PEG) stars are successfully prepared by the combination of epoxide ring-openings and azide-alkyne click reactions. First, monohydroxy-PEG was modified via epoxide chemistry to bear one hydroxyl and one azide functionality at the same end. An alkyne-functionalized PEG chain was then coupled to the azide. Subsequently, the remaining hydroxyl could be reactivated to an azide again and again to enable stepwise addition of alkyne-functionalized polymer arms. The use of efficient reactions for this iterative route provides star polymers with an exact number of arms, and a tailorable degree of polymerization for each arm. Detailed characterization confirms the high purity of multi-arm polyethylene glycol products.

Monitoring polymerization reactions : from fundamentals to applications

With contributions from leading macromolecular scientists and engineers, this book provides a practical guide to polymerization monitoring. It enables laboratory researchers to optimize polymer reactions by providing them with a better understanding of the underlying reaction kinetics and mechanisms. Moreover, it opens the door to improved industrial-scale reactions, including enhanced product quality and reduced harmful emissions.

Monitoring the synthesis and properties of copolymeric polycations.

The kinetics; evolution of molar mass; solution conductivity, sigma; intrinsic viscosity; and average composition drift; and distribution were determined by monitoring the synthesis of copolymeric polycations of acrylamide (Am) and [2-(acryloyloxy)ethyl]-trimethylammonium chloride (Q9). The quantitative relationship between diminishing sigma and charged co-monomers incorporation was monitored for the first time and provided novel data on counterion condensation, which occurs gradually over a broad composition regime. This new capability allows predictions concerning the relationship between copolymer composition and linear charge density, xi, to be tested and models of trivariate mass, composition, and xi distributions to be built. This approach, hence, brings together the previously disparate fields of synthetic chemistry of copolymers and physical chemical properties of polyelectrolytes. Monitoring was achieved with a new implementation of the ACOMP (automatic continuous online monitoring of polymerization reactions) platform. Reactivity ratios determined by ACOMP were rQ9 = 0.47 and rAm = 1.10. Opposite trends in composition drift and final molar mass were found; low starting percentage of Q9 led to low composition drift and high molar mass, whereas the opposite was found at high starting percentage of Q9. Complementary end-product analysis by multidetector gel permeation chromatography supported the ACOMP results. End-product polyelectrolyte properties were characterized by automatic continuous mixing, revealing that combined electrostatic persistence length and excluded volume effects led to the expected large changes in polyelectrolyte conformation and interactions. These results set the groundwork for semibatch control of molar mass, composition, and xi, and eventually for monitoring and control for inverse emulsion-based reactions of this type.

Neutral linear amphiphilic homopolymers prepared by atom transfer radical polymerization

A novel neutral amphiphilic monomer bearing tri(ethylene glycol) monomethyl ether as the hydrophilic part and a decyl group as the hydrophobic part was successfully synthesized and its structure was confirmed by NMR. The monomer was readily polymerized via atom transfer radical polymerization (ATRP) resulting in control over the molecular weight and a narrow dispersity. As a result of the contrasting solubilities of the two side chains, the amphiphilic homopolymers readily self-assembled in a variety of solvents, forming micelles in polar environments and reverse micelles in non-polar environments. The critical micelle concentrations (CMCs) were determined by fluorescence spectroscopy as 0.12 mg mL−1 in hexanes solution and 0.002 mg mL−1 in aqueous solution. The average diameter of the self-assembled aggregates in aqueous solution was calculated by dynamic light scattering (DLS) to be ∼180 nm and this aggregate size was confirmed by transmission electron microscopy (TEM).

Adsorption of copolymers aggregates: from kinetics to adsorbed layer structure.

We examined the adsorption, on hydrophobic and hydrophilic surfaces, of 4 rake-type poly(dimethyl siloxane) (PDMS) copolymers varying the amount of poly(ethylene glycol) (PEG) graft arms from 41 to 72%. The copolymers formed large aggregates in solution, complicating their adsorption kinetics and layer structures. We found the adsorption process always to be dominated by the adsorption of large aggregates, with strongly bound layers resistant to rinsing in adsorbing buffer. Adsorbed amounts were nearly independent of the substrate. However, subtleties in the adsorption kinetics suggested different layer structures for the different systems. On hydrophilic silica, aggregates adsorbed at the transport limited rate until surface saturation, and associated interfacial structures were likely retained. On the hydrophobic surface, a subset of the copolymers exhibited retarded late stage adsorption kinetics suggestive of brush formation. This work demonstrates how subtle differences in adsorption kinetics provide insight into potential interfacial layer structures.

Modular amphiphilic copolymer-grafted nanoparticles: “nanoparticle micelle” behavior enhances utility as dispersants

The majority of existing dispersant systems are based on small molecule amphiphiles and therefore are susceptible to disaggregation when sufficiently diluted. An alternative design is proposed using nanoparticles as a core to template amphiphilic polymers grafted onto their surface into a micelle-like conformation. Such amphiphilic “nanoparticle micelles” will not disaggregate upon dilution, similar to unimolecular micelles. These nanodispersants were prepared by grafting successive blocks of poly(e-caprolactone) and poly(ethylene glycol) from functionalized silica nanoparticles through a combination of surface-initiated ring-opening polymerization and activated ester conjugation chemistry. The swellable hydrophobic poly(e-caprolactone) inner block enabled the encapsulation of a hydrocarbon payload while the hydrophilic poly(ethylene glycol) outer block afforded stable dispersions in aqueous media. Their capacity for hydrocarbon encapsulation was confirmed by their ability to sequester ultraviolet active dyes in aqueous environments and because the length of the polymer blocks can be easily tuned, this design enables the optimization of their loading capacity. Additional characterization using light scattering-based methodologies combined with ultraviolet spectroscopy, 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy, and thermogravimetric analysis experiments confirmed the nanodispersant structure and their “unimolecular micelle-like” behavior.