Multimeric, Multifunctional Derivatives of Poly(ethylene glycol)

Abstract: This article reviews the use of multifunctional polymers founded on high-molecular weight poly(ethylene glycol) (PEG). The design of new PEG derivatives assembled in a dendrimer-like multimeric fashion or bearing different functionalities on the same molecule is described. Their use as new drug delivery systems based on the conjugation of multiple copies or diversely active drugs on the same biocompatible support is illustrated. Keywords: poly(ethylene glycol); multifunctional polymers; conjugation; drug delivery 1. Introduction For the application of biopharmaceuticals in human therapy, the covalent coupling of poly(ethylene glycol) (PEG) chains to drugs, or PEGylation, has been an outstanding innovation. Important pioneering work in this field was performed by Davis and Abuchowski, laying the cornerstone for the commercial success of this technology [1]. Even though many attempts have been undertaken to develop new polymers with improved properties, none of these new substances have been able to compete with poly(ethylene glycol) for this application. This can be explained by the biocompatibility of PEG and the good experience with PEG as a low-cost additive for the pharmaceutical and cosmetic industry over the last decades. An ideal PEG reagent fulfills at least the following criteria: (a)

Efficient Biginelli Synthesis of 2-Aminodihydropyrimidines under Microwave Irradiation

A practical and general method for the Biginelli cyclocondensation of guanidine with aldehydes and \u3b2-dicarbonyl compounds is described and illustrated with the synthesis of a set of 26 functionalized 2-amino-3,4-dihydropyrimidines. The simple protocol involves the \uadmicrowave-mediated reaction of a twofold excess of guanidine hydrochloride with the required reaction partners in an alcohol at 120 \ub0C. Yields are generally good, with short reaction times and a simple workup. The scope is considerably wider than that of similar reactions \uadcarried out under conventional heating

Conjugated PDT drug: photosensitizing activity and tissue distribution of PEGylated pheophorbide a.

The design of new photosensitizers with enhanced phototoxicity and pharmacokinetic properties remains a central challenge for cancer photodynamic therapy (PDT). In this study, Pheophorbide a (Pba) has been pegylated to methoxypolyethylene glycol (mPE G-Pba) to produce a soluble photosensitizer that exhibits a higher tissue distribution than free Pba. In vitro studies have shown that mPE G-Pba promotes a fairly strong photosensitizing effect in cancer cells, as previously observed for the unpegylated molecule. mPE G-Pba targets the mitochondria where, following photoactivation, ROS are produced which cause a cellular injury by lipid peroxidation. The effect of pegylation on the photosensitizer biodistribution has been examined in different selected organs of female mice, at different time points after intraperitoneal administration of the drug (50 μmol/Kg body weight). Other than free Pba, which showed a low tissue accumulation, mPE G-Pba has been detected in significant amounts (8 to 16 μg/ml) in liver, spleen, duodenum and kidney and, 3-5 hours after intraperitoneal injection, in moderate amounts (3 to 8 μg/ml) in brain and lung. In vivo optical imaging performed on living female C57/BL6 mice bearing a subcutaneous melanoma mass, showed that injected mPEG-Pba distributes all over the body, with an higher uptake in the tumor respect to free Pba. Our results indicate that although pegylation somewhat decreases the phototoxicity, it significantly increases the drug solubility and tissue distribution and tumor uptake of mPE G-Pba, making the conjugate an interesting photosensitizer for PDT

BIOCONVERSIONI DI DIALCHIL 2-CHETODIESTERI: FUNZIONALIZZATI MEDIANTE SACCHAROMYCES CEREVISIAE ED ENZIMI IDROLITICI

1997/1998XI Ciclo1968Versione digitalizzata della tesi di dottorato cartacea

Radice

Il mio contributo, che vuole essere un esercizio creativo, espone sinteticamente alcune sfumature filosofiche che possono ruotare attorno alla parola "Radice", traendo ispirazione, soprattutto, dal dettato della fenomenologia di Edmund Husserl

Mixed matrix membranes for hydrocarbons separation and recovery: a critical review

The separation and purification of light hydrocarbons are significant challenges in the petrochemical and chemical industries. Because of the growing demand for light hydrocarbons and the environmental and economic issues of traditional separation technologies, much effort has been devoted to developing highly efficient separation techniques. Accordingly, polymeric membranes have gained increasing attention because of their low costs and energy requirements compared with other technologies; however, their industrial exploitation is often hampered because of the trade-off between selectivity and permeability. In this regard, high-performance mixed matrix membranes (MMMs) are prepared by embedding various organic and/or inorganic fillers into polymeric materials. MMMs exhibit the advantageous and disadvantageous properties of both polymer and filler materials. In this review, the influence of filler on polymer chain packing and membrane sieving properties are discussed. Furthermore, the influential parameters affecting MMMs affinity toward hydrocarbons separation are addressed. Selection criteria for a suitable combination of polymer and filler are discussed. Moreover, the challenges arising from polymer/filler interactions are analyzed to allow for the successful implementation of this promising class of membranes

An Efficient Synthesis of Chiral Non\u2010Racemic Hydroxyalkanoic Acids by Olefin Cross\u2010Metathesis Reactions

Cross-metathesis reactions of 1-hepten-3-ol, 1-octen-4-ol, 1-octen-4-yl acetate and 1-tetradecen-4-ol with unsaturated methyl esters were investigated to optimize the synthesis of methyl hydroxyalkenoates, precursors of hydroxyalkanoic acids. Various commercially available catalysts, concentration ratios of reagents as well as microwave irradiation were explored. (R)-8-hydroxydodecanoic acid and (S)-8-hydroxystearic acid were successfully obtained in 3 steps from enantiomerically enriched alcohols

Multimeric, Multifunctional Derivatives of Poly(ethylene glycol)

This article reviews the use of multifunctional polymers founded on high-molecular weight poly(ethylene glycol) (PEG). The design of new PEG derivatives assembled in a dendrimer-like multimeric fashion or bearing different functionalities on the same molecule is described. Their use as new drug delivery systems based on the conjugation of multiple copies or diversely active drugs on the same biocompatible support is illustrated

PEG\u2013Ursolic Acid Conjugate: Synthesis and In Vitro Release Studies

A highly water-soluble macromolecular compound of ursolic acid with mono-methoxypoly(ethylene glycol) (mPEG) was prepared. The physicochemical properties and stabilities under different conditions were investigated. By PEG conjugation, greatly increased water solubility was obtained, and the results showed that this conjugate was a potential prodrug for the oral delivery of ursolic acid