Current Medicinal Chemistry - Volume 21, Issue 29, 2014

Microbial biofilms are associated with drastically enhanced resistance to most of the antimicrobial agents and with frequent treatment failures, generating the search for novel strategies which can eradicate infections by preventing the persistent colonization of the hospital environment, medical devices or human tissues. Some of the current approaches for fighting biofilms are represented by the development of novel biomaterials with increased resistance to microbial colonization and by the improvement of the current therapeutic solutions with the aid of nano(bio)technology. This special issues includes papers describing the applications of nanotechnology and biomaterials science for the development of improved drug delivery systems and nanostructured surfaces for the prevention and treatment of medical biofilms. Nanomaterials display unique and well-defined physical and chemical properties making them useful for biomedical applications, such as: very high surface area to volume ratio, biocompatibility, biodegradation, safety for human ingestion, capacity to support surface modification and therefore, to be combined with other bioactive molecules or substrata and more importantly being seemingly not attracting antimicrobial resistance. The use of biomaterials is significantly contributing to the reduction of the excessive use of antibiotics, and consequently to the decrease of the emergence rate of resistant microorganisms, as well as of the associated toxic effects. Various biomaterials with intrinsic antimicrobial activity (inorganic nanoparticles, polymers, composites), medical devices for drug delivery, as well as factors influencing their antimicrobial properties are presented. One of the presented papers reviews the recent literature on the use of magnetic nanoparticles (MNP)-based nanomaterials in antimicrobial applications for biomedicine, focusing on the growth inhibition and killing of bacteria and fungi, and, on viral inactivation. The anti-pathogenic activity of the most common types of metallic/metal oxide nanoparticles, as well as the photocontrolled targeted drug-delivery system and the development of traditional Chinese herbs nanoparticles are some of the highlights of another paper of this issue. The applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization are also discussed, as well as one of the most recent paradigms of the pharmaceutical field and nanobiotechnology, represented by the design of smart multifunctional polymeric nanocarriers for controlled drug delivery. These systems are responding to physico-chemical changes and as a result, they can release the active substances in a controlled and targeted manner. The advantages and limitations of the main routes of polymerization by which these nanovehicles are obtained, as well as the practical appllications in the field of drug nanocarriers are presented. The authors describe the therapeutic applications of dendrimers, which are unimolecular, monodisperse nanocarriers with unique branched tree-like globular structure. The applications of nanotechnology for the stabilization and improved release of anti-pathogenic natural or synthetic compounds, which do not interfere with the microbial growth, but inhibit different features of microbial pathogenicity are also highlighted. We expect this special issue would offer a comprehensive update and give new directions for the design of micro/nano engineered materials to inhibit microbial colonization on the surfaces or to potentiate the efficiency of the current/ novel/alternative antimicrobial agents by improving their bioavailability and pharmacokinetic features.

The increasing morbidity and mortality of infectious diseases is an increasing concern. Despite the continuous development and synthesis of new antimicrobial drugs, microbial pathogens are exhibiting increased multi-drug resistance. Nanomaterials display unique and well-defined physical and chemical properties including a very high surface area to volume ratio, and new approaches for antimicrobial therapies have attempted to combine nanomaterials and current antimicrobial drugs. Magnetic nanoparticles (MNPs) are characterized by biocompatibility, biodegradation, and safety for human ingestion. Iron oxide nanoparticles have been approved for human use by the US Food and Drug Administration (FDA). For biomedicine applications, MNPs require surface modification to become water-soluble and be stable enough to resist the effects of proteins and salts in the physiological environment. MNPs can combine various substrata, such as biomolecules and nanomaterials to generate new antimicrobial agents which combine antibacterial, antiviral, and antifungal properties. This can be accomplished through a series of surface modification methods. Because MNPs have unique superparamagnetic characteristics, they can be controlled and recycled by an external magnetic field.In addition, the antimicrobial activity of MNPs–based nanocomposites is superior to that of metallic nanoparticles. This paper reviews the recent literature on the use of MNP-based nanomaterials in antimicrobial applications in biomedicine. Antimicrobial applications mainly focus on inhibiting and killing bacteria and fungi and viruses inactivation. The synthesis, surface modification, and characteristics related to MNPs will also be briefly addressed.

Bacterial and cancer cells that are resistant to current specific therapy have become an increasingly important public health problem over the past several decades. Consequently, the search for new anti-infection and anti-cancer treatments of drug resistant microbes has attracted a lot of attention. Recently, nanostructures have been shown to be efficient antimicrobial agents that do not induce drug-resistance. The present study reviews the advances in anti-pathogenic bio-hybrid nanostructures over the past decade. Three important issues are presented and discussed. First, the review focuses on the anti-pathogenic activity of the most common types of metallic / metal oxide nanoparticles. It not only reviews the progress of antimicrobial characteristics for various types of nanoparticles under different fabrication processes, but it also tabulates some specific findings over the past decade. Secondly, it reviews the use of polymeric, gold and iron-oxide nanoparticles as effective chemotheraputic drug carriers or for gene transduction in cancer treatment. Finally, some new advances made in Taiwan in anti-pathogenic research using nanotechnology were addressed in brief at the end of this paper. We highlighted the advances of the photo-controlled targeted drug-delivery system and the development of nanoparticles of traditional Chinese herbs, both of which representing important milestones in the last decade.

Smart multifunctional polymeric nanocarriers able to respond to physicochemical changes in their environment or to external stimuli represent a new paradigm in the field of pharmaceutical formulations for controlled drug delivery. The introductory part of the present review deals with this new concept and presents the main advantages resulting from the use of such nanovehicles instead of conventional, much larger drug delivery systems. The access to drug nanocarriers based on smart supramolecular polymeric materials is primarily limited by the available polymerization methods capable to produce polymers with low polydispersity index, as well as much more complex macromolecular architectures with strictly controlled chemical composition, such as block copolymers and star or graft polymers or copolymers. This article reviews the state-of-the art in controlled/"living" free radical polymerization techniques as well as ring opening polymerization methods. Nitroxide mediated free radical polymerization (NMP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain-transfer polymerization (RAFT), single electron transfer-living radical polymerization (SET-LRP), single electron transfer-nitroxide radical coupling reaction (SET-NRC), cationic ring opening polymerization (CROP), anionic ring opening polymerization (AROP), and metal catalyzed ring opening polymerization are described, highlighting their mechanistic details and their synthetic potential as well as their limitations. The final part of the article is dedicated to a special type of unimolecular, monodisperse nanocarriers - the dendrimers. Both divergent and convergent approaches to dendrimer synthesis are described along with the therapeutic applications taking advantage of the unique branched tree-like globular structure of dendrimers to treat cancer.

Due to the great prevalence of persistent and recurrent implanted device associated-infections novel and alternative therapeutic approaches are intensely investigated. For reducing complications and antibiotic resistance development, one major strategy is using natural or synthetic modulators for targeting microbial molecular pathways which are not related with cell multiplication and death, as Quorum Sensing, virulence and biofilm formation. The purpose of this review paper is to discuss the most recent in vitro approaches, investigating the efficiency of some novel antimicrobial products and the nano-technologic progress performed in order to increase their effect and stability.

The emergence of antibiotic resistance in microbial strains is representing one of the major threats to public health worldwide, due to the decreased or total cancelling of the available antibiotics effectiveness, correlated with the slow development of novel antibiotics. Due to their excellent biodegradability and biocompatibility, the synthetic polymers could find a lot of biomedical applications, such as the development of biomaterials with optimized properties and of drug delivery systems. This review is focusing on the applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization

The present review is intended to bring together the main advances in the field of nanostructured biomaterials with antimicrobial properties. It is generally accepted that the discovery of antibiotics was of great importance but, nowadays new antimicrobial agents are needed and/or their better administration routes. The limitation of the use of antibiotics is essential because of the following reasons: the excessive use of antibiotics leads to the development of antibiotic resistant microorganisms; there are some alternatives for many types of infections, many of these alternatives being less toxic and do not lead to antibiotic similar resistance. In compliance with the above presented, the use of antibiotic is recommended to be eliminated (when alternatives are available) or to be reduced by using combined therapy when possible or to administrate these drugs through targeted or loco-regional drug delivery systems.