Hybrid nanogels by direct mixing of chitosan, tannic acid and magnetite nanoparticles: processes involved in their formation and potential catalytic properties.

Magnetite (FeO) nanoparticles (MNPs) as nanocatalysts have drawn considerable attention because of their unique properties such as peroxidase-like activity. However, their biodistribution and availability for specific treatments still need to be improved. In this study, a simple and convenient strategy for the synthesis of hybrid nanogels (NGs) is described, which involves direct mixing of biomaterials such as chitosan (Ch) and tannic acid (TA), with the incorporation of MNPs, under oxidising conditions, using the inverse nanoemulsion method.

Combining ZnPc-liposomes and chitosan on a hybrid matrix for enhanced photodynamic therapy.

Photodynamic therapy is an alternative treatment for several pathologies, including cancer. This therapy uses a photosensitizer capable of producing reactive oxygen species through irradiation, promoting cellular death. A limitation of photosensitizers is their low solubility in aqueous media.

Ascidian-Inspired Supramolecular Cellulose Nanocomposite Hydrogels with Antibacterial Activity.

The design of ultratough hydrogels has recently emerged as a topic of great interest in the scientific community due to their ability to mimic the features of biological tissues. An outstanding strategy for preparing these materials relies on reversible and dynamic cross-links within the hydrogel matrix. In this work, inspired by the composition of ascidians' tunic, stretchable supramolecular hydrogels combining poly(vinyl alcohol), green tea-derived gallic acid, and rigid tannic acid-coated cellulose nanocrystals (TA@CNC) were designed.

Controlled Thermoreversible Formation of Supramolecular Hydrogels Based on Poly(vinyl alcohol) and Natural Phenolic Compounds.

Supramolecular hydrogels have promising applications in a wide variety of fields including 3D bioprinting, sensors and actuators, biomedicine, and controlled drug delivery. This communication reports the facile reversible thermotriggered formation of novel pH-responsive supramolecular hydrogels based on poly(vinyl alcohol) (PVA) bonded via dynamic H-bridge with small phenolic biomolecules. PVA and phenolic compounds form a clear solution when they are physically mixed in water at high temperature, but a fast gelation is produced at room temperature through multiple strong H-bonding interactions.

Poly(N-vinylcaprolactam) Nanogels with Antiviral Behavior against HIV-1 Infection.

Stimuli-responsive nanogels offer promising perspectives for the development of next generation formulations for biomedical applications. In this work, poly(N-vinylcaprolactam) nanogels were synthesized varying the concentration of monomer and crosslinking agent. Thus, the inhibitory effect of poly(N-vinylcaprolactam) nanogels against HIV-1 infection is presented for the first time.

Semi-interpenetrated, dendritic, dual-responsive nanogels with cytochrome c corona induce controlled apoptosis in HeLa cells.

The use of thermoresponsive nanogels (NGs) allows the controlled release of therapeutic molecules upon a thermal switch. Usually, this strategy involves the use of temperature increase to activate cargo expulsion from shrinking NGs. In this study, poly(N-isopropylacrylamide) (pNIPAM)-based NGs were involved in the release of a therapeutic protein corona by temperature decrease.

Multi-kinetic release of benznidazole-loaded multiparticulate drug delivery systems based on polymethacrylate interpolyelectrolyte complexes.

Interpolyelectrolyte complexes (IPEC) formulated as multiparticulate drug delivery systems (MDDS) are interesting carriers to improve drug' performance. Benznidazole (BZ) is the first-line drug for Chagas treatment; however, it presents side effects and toxicity, conditioning its efficacy and safety. The goal of this work was to obtain novel MDDS composed by IPEC based on different polymethacrylate carriers loaded with BZ and to investigate in vitro drug delivery performance for oral administration.

Bioadhesive and biocompatible films as wound dressing materials based on a novel dendronized chitosan loaded with ciprofloxacin.

The bioadhesive polymeric films as topical drug delivery systems are interesting alternatives to improve the pharmacotherapy and patient compliances. New derivate biomaterials based on weisocyanate- dendronized PVP- crosslinked chitosan and loaded with ciprofloxacin (CIP), as model drug, were used to prepare bioadhesive films. Relevant in vitro/in vivo attributes to define main physicochemical and biopharmaceutical characteristics for topical wound-healing applications were evaluated.

Formation and characterization of Langmuir and Langmuir-Blodgett films of Newkome-type dendrons in presence and absence of a therapeutic compound, for the development of surface mediated drug delivery systems.

Organic macromolecules with dendrimeric architectures are polymeric materials potentially useful as nanocarriers for therapeutic drugs. In this work, we evaluate a series of Newkome-type dendrons in Langmuir and Langmuir-Blodgett films as platforms capable of interacting with a potential antitumoral agent. The nanocomposite is proposed as model for the development of surface mediated drug delivery systems.

Multifunctional Nanomaterials: Design, Synthesis and Application Properties.

The immense scope of variation in dendritic molecules (hyper-branching, nano-sized, hydrophobicity/hydrophilicity, rigidity/flexibility balance, etc.) and their versatile functionalization, with the possibility of multivalent binding, permit the design of highly improved, novel materials. Dendritic-based materials are therefore viable alternatives to conventional polymers.

Camptothecin-7-yl-methanthiole: semisynthesis and biological evaluation.

The introduction of a methylenthiol group at position 7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound.

Synthesis of (+)-dumetorine and congeners by using flow chemistry technologies.

An efficient total synthesis of the natural alkaloid (+)-dumetorine by using flow technology is described. The process entailed five separate steps starting from the enantiopure (S)-2-(piperidin-2-yl)ethanol 4 with 29% overall yield. Most of the reactions were carried out by exploiting solvent superheating and by using packed columns of immobilized reagents or scavengers to minimize handling.

Efficient continuous flow synthesis of hydroxamic acids and suberoylanilide hydroxamic acid preparation.

A continuous flow tubing reactor can be used to readily transform methyl or ethyl carboxylic esters into the corresponding hydroxamic acids. Flow rate, reactor volume, and temperature were optimized for the preparation of a small collection of hydroxamic acids. Synthetic advantages were identified as an increased reaction rate and higher product purity.

Electrochemical study of a dendritic family at the water/1,2-dichloroethane interface.

The transfer of six dendritric molecules, DMs, across the water/1,2-dichloroethane interface was investigated using cyclic voltammetry. From the variation of peak potential with pH, two different mechanisms of transfer were postulated depending on the nature of the molecules. Voltammetric parameters were employed to evaluate the hydrophilic/hydrophobic character and calculate the acid dissociation constant of these molecules.

Synthesis and biological evaluation of novel dimiracetam derivatives useful for the treatment of neuropathic pain.

Chemical modifications of dimiracetam, a bicyclic analogue of the nootropic drug piracetam, afforded a small set of novel derivatives that were investigated in in vivo models of neuropathic pain. Compounds 5, 7 and 8 displayed a very promising antihyperalgesic profile in rat models of neuropathic pain induced by both chronic constriction injury of the sciatic nerve and streptozotocin. The compounds completely reverted the reduction of pain threshold evaluated by the paw pressure test.

Enantioselective formal synthesis of uleine alkaloids from phenylglycinol-derived bicyclic lactams.

A two-step route for the enantioselective construction of the tetracyclic ring system of uleine alkaloids, involving the stereoselective conjugate addition of an appropriate indole-containing nucleophile to a chiral bicyclic delta-lactam and the subsequent cyclization on the indole 3-position of the resulting 4,5-disubstituted 2-piperidone, has culminated in the formal total synthesis of several alkaloids of this group.

Antagonists at the neurokinin receptors--recent patent literature.

This review describes the patent applications and relevant scientific literature published during 2002 in the field of novel neurokinin receptor antagonists, with an emphasis on the medicinal chemistry of recent patent publications. A brief update on the development status of compounds including: the neurokinin-1 receptor antagonists aprepitant (Merck & Co Inc), vofopitant, ezlopitant (Pfizer Inc), R-673 (F Hoffmann-La Roche Ltd); the neurokinin-2 receptor antagonists nepadutant (Menarini Ricerche SpA), saredutant (Sanofi-Synthelabo), SR-144190 (Sanofi-Synthelabo) and UK-290795 (Pfizer Inc); and the neurokinin-3 receptor antagonists osanetant (Sanofi-Synthelabo) and talnetant (GlaxoSmithKline plc) will be given. The review also reports the recent published patent literature in the area of novel therapeutic uses and novel formulations and combinations claimed for neurokinin receptor antagonists.

Ibogaine analogues. Synthesis and preliminary pharmacological evaluation of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes.

Synthesis of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes by cycloaddition and subsequent cross-coupling reaction is described.