Current Topics in Medicinal Chemistry - Volume 15, Issue 3, 2015

The present review deals with the sol-gel imprinting of both drug and non-drug templates of medical relevance, namely neurotransmitters, biomarkers, hormones, proteins and cells. Nearly a hundred recent works, either developmental or applied in a medical-related context, were critically analyzed. It may be concluded that, although research is still at an early stage, the potential of these sol-gel materials was well demonstrated in a few applications of critical interest for medicinal/biomedical science. The vast room left for expansion and improvement envisages a continuously growing interest by researchers in the future, eventually resulting in important medical applications able to enter the professional and consumer medical markets.

The sol-gel process provides a robust and versatile technology for the immobilization of biologicals. A wide range of inorganic, composites and hybrid materials can be prepared to encapsulate molecular drugs, proteins, antibodies/antigens, enzymes, nucleic acids, prokaryotic and eukaryotic cells into bulk gels, particles and films. This review describes the applications of sol-gel encapsulation relevant to medicinal chemistry focusing on the recent development of biosensors as well as systems for production, screening and delivery of bioactive compounds and biomaterials.

Biosensors have opened new horizons in biomedical analysis, by ensuring increased assay speed and flexibility, and allowing point-of-care applications, multi-target analyses, automation and reduced costs of testing. This has been a result of many studies merging nanotechnology with biochemistry over the years, thereby enabling the creation of more suitable environments to biological receptors and their substitution by synthetic analogue materials. Sol-gel chemistry, among other materials, is deeply involved in this process. Sol-gel processing allows the immobilization of organic molecules, biomacromolecules and cells maintaining their properties and activities, permitting their integration into different transduction devices, of electrochemical or optical nature, for single or multiple analyses. Sol-gel also allows to the production of synthetic materials mimicking the activity of natural receptors, while bringing advantages, mostly in terms of cost and stability. Moreover, the biocompatibility of sol-gel materials structures of biological nature allowed the use of these materials in emerging in vivo applications. In this chapter, biosensors for biomedical applications based on sol-gel derived composites are presented, compared and described, along with current emerging applications in vivo, concerning drug delivery or biomaterials. Sol-gel materials are shown as a promising tool for current, emerging and future medical applications.

Sol-gel chemistry allows the immobilization of organic molecules of biological origin on suibtable solid supports, permitting their integration into biosensing devices widening the possibility of local applications. The present work is an application of this principle, where the link between electrical receptor platform and the antibody acting as biorecognition element is made by sol-gel chemistry. The immunosensor design was targeted for carcinoembryonic antigen (CEA), an important biomarker for screening the colorectal cancer, by electrochemical techniques, namely electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SVW). The device displayed linear behavior to CEA in EIS and in SWV assays ranging from 0.50 to 1.5ng/mL, and 0.25 to 1.5ng/mL, respectively. The corresponding detection limits were 0.42 and 0.043 ng/mL. Raman spectroscopy was used to characterize the surface modifications on the conductive platform (FTO glass). Overall, simple sol-gel chemistry was effective at the biosensing design and the presented approach can be a potential method for screening CEA in point-of-care, due to the simplicity of fabrication, short response time and low cost.

Different silicon-based xero-gel molecularly imprinted spheres in the nano boundary range with recognition capabilities for nafcillin have been synthesised, using tetraethylorthosilicate (TEOS) and (3- aminopropyl) triethoxysilane (APTEOS) as precursors. Imprinting has been achieved using both nafcillin (NAF) or structural analogous ‘dummies’ such as (+)-6-aminopenicillenic acid (APA), or ampicillin ((+)-6- aminobenzylpenicillin)sodium salt (AMP). Materials were fully characterized using ATR-FTIR, 29Si solidstate NMR, TGA, TEM and BET. Adsorption isotherms for all the materials fit with a continuous Freundlich model with correlation coefficients better than 0.988 and mean affinity constants between 105 and 106 L·mol-1. The use of ‘dummies’ as well as the template itself in the imprinting process resulted in materials with different release speed. Combinations of these materials allow designing mixtures with a continuous, controlled and constant release longer than four days. Thus, the non-imprinted and the AMP-imprinted material have a rapid release during the first five hours, nafcillin and APA imprinted ones release antibiotic mainly after a latency-period of 24 hours.

Today biomedical sciences are experiencing the importance of imaging biological parameters with luminescence methods. Studying 2D pH distribution with those methods allows building knowledge about complex cellular processes. Immobilizing pH sensitive nanoparticles inside hydrogel matrixes, in order to guarantee a proper SNR, could easily make stable and biocompatible 2D sensors. Inkjet printing is also well known as tool for printing images onto porous surfaces. Recently it has been used as a free-form fabrication method for building three-dimensional parts, and now is being explored as a way of printing electrical and optical devices. Inkjet printing was used either as a rapid prototyping method for custom biosensors. Sol-gel method is naturally bound with inkjet, because the picoliter-sized ink droplets evaporate quickly, thus allowing quick sol-gel transitions on the printed surface. In this work will be shown how to merge those technologies, in order to make a nanoparticles doped printable hydrogel, which could be used for making 2D/3D smart scaffolds able to monitor cell activities. An automated image analysis system was developed in order to quickly have the pH measurements from pH nanosensors fluorescence images.