In recent years, tools for the development of new drugs have been dramatically improved. These include genomic and proteomic research, numerous biophysical methods, combinatorial chemistry and screening technologies. In addition, early ADMET studies are employed in order to significantly reduce the failure rate in the development of drug candidates. As a consequence, the lead finding, lead optimization and development process has gained marked enhancement in speed and efficiency. In parallel to this development, major pharma companies are increasingly outsourcing many components of drug discovery research to biotech companies. All these measures are designed to address the need for a faster time to market. New screening methodologies have contributed significantly to the efficiency of the drug discovery process. The conventional screening of single compounds or compound libraries has been dramatically accelerated by high throughput screening methods. In addition, in silico screening methods allow the evaluation of virtual compounds. A wide range of new lead finding and lead optimization opportunities result from novel screening methods by NMR, which are the topic of this review article.

Drug Discovery Today

Nanocomposite hydrogels are polymeric networks that possess a unique property of hydration. The presence of alcohols, carboxylic acids and amides as hydrophilic moieties in structure of nanocomposite hydrogels enhances their stiffness and water-absorbing capacity. Addition of cross-linker in the synthesis of hydrogels increases their stability under extreme conditions of temperature, pH and pressure. Natural polymer-based nanocomposite hydrogels are biodegradable, highly hydrophilic and possess good mechanical strength. Gelatin, chitin, cellulose, pectin, carrageenan, starch and alginate are natural polymers commonly used to fabricate nanocomposite hydrogels. Nanocomposite hydrogels have special characteristics such as high swelling rate, selectivity and stimuli-sensitive nature. Here we review nanocomposite hydrogels for environmental protection and biomedical engineering. Applications in biomedical engineering include drug delivery agents, wound dressing, tissue engineering and antibacterials. Applications in environmental protection include ion exchangers, adsorption, photocatalysis and soil conditioning. Many nanocomposite hydrogels show excellent adsorption selectivity for heavy metal ions: Cu2+ up to 30.35 mg/g, Pb2+ up to 35.94 mg/g, and Zn2+ and Fe3+ up to 94.34 mg/g. Xanthan gum-based nanocomposite hydrogel has removed 96% dye from industrial effluent as reported. In addition, most of the nanocomposite hydrogels showed better adsorption capacity for pollutants in the pH range from 5 to 7. The nanocomposite hydrogels could also be regenerated and successfully utilized for several times. Nanocomposite hydrogels are therefore good bio-absorbent materials for environmental detoxification.

Applications of nanocomposite hydrogels for biomedical engineering and environmental protection

Facile Access to Multisensitive and Self-Healing Hydrogels with Reversible and Dynamic Boronic Ester and Disulfide Linkages

Fast responsive macroporous interpenetrating polymer network (IPN) hydrogels were fabricated in this work by a sequential strategy, as follows: the first network, consisting of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEM) cross-linked with N,N′-methylenebisacrylamide (BAAm), was prepared at −18 °C, the second network consisting of poly(acrylamide) (PAAm) cross-linked with BAAm, being also generated by cryogelation technique. Both single network cryogels (SNC) and IPN cryogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and water uptake. The presence of weak polycation PDMAEM endows the SNCs and the IPNs cryogels with sensitivity at numerous external stimuli such as pH, temperature, ionic strength, electric field, among which the first three were investigated in this work. It was found that the initial concentration of monomers in both networks was the key factor in tailoring the properties of IPN cryogels such as swelling kinetics, equilibrium water c...

Smart Macroporous IPN Hydrogels Responsive to pH, Temperature, and Ionic Strength: Synthesis, Characterization, and Evaluation of Controlled Release of Drugs.

The application of organic polymers and inorganic/organic hybrid systems in numerous fields of biotechnology has seen a considerable growth in recent years. Typically, organic polymers with diverse structures, compositional variations and differing molecular weights have been utilized to assemble polymeric nanosystems such as polymeric micelles, polymersomes, and nanohydrogels with unique features and structural properties. The architecture of these polymeric nanosystems involves the use of both hydrophobic and hydrophilic polymeric blocks, making them suitable as vehicles for diagnostic and therapeutic applications. Recently, "smart" or "intelligent" polymers have attracted significant attention in the biomedical field wherein careful introduction of specific polymeric modalities changes a banal polymeric nanosystem to an advanced stimuli-responsive nanosystem capable of performing extraordinary functions in response to an internal or external trigger such as pH, temperature, redox, enzymes, light, magnetic, or ultrasound. Further, incorporation of inorganic nanoparticles such as gold, silica, or iron oxide with surface-bound stimuli-responsive polymers offers additional advantages and multifunctionality in the field of nanomedicine. This review covers the physical properties and applications of both organic and organic/inorganic hybrid nanosystems with specific recent breakthroughs in drug delivery, imaging, tissue engineering, and separations and provides a brief discussion on the future direction.

Polymer-based stimuli-responsive nanosystems for biomedical applications.

This study deals with the preparation of novel multiresponsive (magnetoresponsive, thermoresponsive and pH-responsive) nanocomposite conetworks consisting of oleic acid-coated magnetite nanoparticles (OA·Fe3O4), hydrophilic/thermoresponsive hexa(ethylene glycol) methyl ether methacrylate (HEGMA), hydrophobic/metal binding 2-(acetoacetoxy)ethyl methacrylate (AEMA), and pH-responsive/thermoresponsive N-diethylaminoethyl methacrylate (DEAEMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) moieties. Conventional free radical copolymerization was employed for the synthesis of random conetworks in the absence and presence of preformed OA·Fe3O4. Further, in characterization of these materials in regards to their swelling behavior in organic and aqueous solvents, thermal/thermoresponsive properties, and composition, assessment of their magnetic characteristics disclosed tunable superparamagnetic behavior. These systems were also evaluated toward their ability to adsorb and release a solute (benzoic acid) in a c...

Multiresponsive Polymer Conetworks Capable of Responding to Changes in pH, Temperature, and Magnetic Field: Synthesis, Characterization, and Evaluation of Their Ability for Controlled Uptake and Release of Solutes

Maria Christodoulou

Papers

Multiresponsive Polymer Conetworks Capable of Responding to Changes in pH, Temperature, and Magnetic Field: Synthesis, Characterization, and Evaluation of Their Ability for Controlled Uptake and Release of Solutes