Current Pharmaceutical Design - Volume 24, Issue 8, 2018

Hydrogels, as a class of materials for tissue engineering and drug delivery, have high water content and solid-like mechanical properties. Currently, hydrogels with an antibacterial function are a research hotspot in biomedical field. Many advanced antibacterial hydrogels have been developed, each possessing unique qualities, namely high water swellability, high oxygen permeability, improved biocompatibility, ease of loading and releasing drugs and structural diversity. In this article, an overview is provided on the preparation and applications of various antibacterial hydrogels. Furthermore, the prospects in biomedical researches and clinical applications are predicted.

The rising incidence of antibiotic-resistant infections, combined with a declining number of new antibiotic drug approvals, has generated an alarming therapeutic gap that critically undermines public health. Host Defense Peptides (HDPs), sometimes referred to as “Nature's Antibiotics”, are short chain, amphiphilic and cationic peptide sequences found in all multicellular organisms as part of their innate immunity. While there is a vast diversity in terms of HDP sequence and secondary structure, they all seem to share physiochemical characteristics that can be appropriated for macromolecular design by the synthetic polymer chemist. Over the past decade, remarkable progress has been made in the design and synthesis of polymer-based materials that effectively mimic HDP action – broad-spectrum antibacterial potency, rapid bactericidal kinetics, and minimal toxicity to human cells – while offering the additional benefits of low cost, high scalability, and lower propensity to induce resistance, relative to their peptide-based counterparts. A broad range of different macromolecular structures and architectures have been explored in this design space, including polynorbornenes, poly(meth)acrylates, poly(meth)acrylamides, nylon-2 polymers, and polycarbonates, to name a just few. Across all of these diverse chemical categories, the key determinants of antibacterial and hemolytic activity are the same as in HDPs: net cationic charge at neutral pH, well-balanced facial amphiphilicity, and the molecular weight of the compounds. In this review, we focus in particular on recent progress in the polymethacrylate category first pioneered by Kuroda and DeGrado and later modified, expanded upon and rigorously optimized by Kuroda's and many other groups. Key findings and future challenges will be highlighted.

The risk of bacterial colonization of abiotic surfaces of biomedical devices poses important challenges for the pharmaceutical and biomaterials science fields. In this scenario, antibacterial coatings have been developed, using a number of different molecules and materials. Among them, chitosan is a non-cytotoxic, biocompatible biopolymer with an inherent antimicrobial activity that has been already used in a wide variety of healthcare and industrial applications. Herein, chitosan-based antibacterial coatings are critically surveyed, with a special emphasis on their production methods, pharmaceutical and biomedical applications, along with their pros and cons, and finally highlighting the key challenges to be faced and future perspectives in this field.

Infections caused by microbial proliferation are one of the common issues and serious threats to the medical care, and they usually result in disease spread. Therefore, it is a significant issue for developing the antiinfective biomaterials to control this problem, according to the specific clinical application. Meanwhile, all their properties, the best anti-infective performance, the safe biocompatibility and the appropriate tissue interactions must be conformed to each other. At present, technologies are developing novel biomaterials and surfaces endowed with anti-infective properties, relying either on bactericidal or anti-biofilm activities. This review focuses on thoroughly summarizing numerous kinds of antibacterial biomaterials, including the antibacterial matrix biomaterials, antibacterial coatings and films, nanostructured materials and antibacterial fibers. Among these strategies, the utilization of bio-glass base and graphene base antibacterial matrix, and their effects on the antibiosis mechanism were emphatically discussed. Simultaneously, the effects and mechanisms of nano-coated metallic ions are also mentioned. Overall, there is a wealth of technical solutions to contrast the establishment of an implant infection. The lack of well-structured prospective multicenter clinical trials hinders the achievement of conclusive data on the efficacy and comparative performance of antibacterial biomaterials.

Metal oxide nanoparticles (MO-NPs) are known to effectively inhibit the growth of a wide range of Gram-positive and Gram-negative bacteria. They have emerged as promising candidates to challenge the rising global issue of antimicrobial resistance. However, a comprehensive understanding of their mechanism of action and identifying the most promising NP materials for future clinical translation remain a major challenge due to variations in NP preparation and testing methods. With various types of MO-NPs being rapidly developed, a robust, standardized, in vitro assessment protocol for evaluating the antibacterial potency and efficiency of these NPs is needed. Calculating the number of NPs that actively interact with each bacterial cell is critical for assessing the dose response for toxicity. Here we discuss methods to evaluate MO-NPs antibacterial efficiency with focus on issues related to NPs in these assays. We also highlight sources of experimental variability including NP preparation, initial bacterial concentration, bacterial strains tested, culture microenvironment, and reported dose.

The antimicrobial peptides (AMPs) are a group of unique naturally occurring anti-microbial compounds with around 50 amino acids. It represents promising therapeutic agents to the infectious disease without concerning about drug resistance. However, commercial development of these peptides for even the simplest application has been hindered by the limitations of sources, instability, toxicity and bioavailability. To improve the properties of the artificial synthesized AMPs, the modification and design are the hotspots of the AMPs research. In fact, more than half of the known AMPs are naturally modified. In this review, two types of modification strategies, biochemical modification and chemical modification were summarized. Although, the chemical modification is versatile and direct, the manufacturing cost is greatly increased compared to the antibiotics. With the recent progress of the protein modification enzyme, the biochemical modification of the antimicrobial peptide followed by heterologous expression has great application prospects.

Traditional use of antibiotics through injection or oral ingestion has many disadvantages, such as detrimental side effects in the host, less effectiveness, high and repeated doses, and development of drug resistance. For prevention and treatment of implant-associated infections, the continuous local delivery of antibiotics is required. Thus, there is a strong demand for the development of drug carrier systems to control the release of antibiotics in a moderate manner over an appropriate timescale. This review summarizes the carrier platforms used for the loading of antibiotics, and highlights their drug release behaviors as well as in vitro and in vivo antibacterial properties.

Construction of antibacterial surfaces or films is of great interest in various fields including biomedicine, food, agriculture and so on. So far, a number of antibacterial agents have been used to construct antibacterial surfaces. Layer-by-Layer (LbL) assembly is a simple and versatile deposition process for fabricating multilayer thin films with great advantages to control the architecture and composition of the films. In this review, we give a brief introduction of LbL, and different materials used to fabricate antibacterial surfaces with LbL assembly approach are described as well as their drawbacks. Much attention is also paid to the recent development of multifunctional and intelligent antibacterial surfaces. Moreover, the advantages and limitations of these different types of antibacterial materials are summarized and subsequently directions for future development are proposed.

Wound management is an important and increasing global issue. Infection of a wound can cause a delay in wound healing and pain, but also more serious complications like tissue necrosis or even sepsis, which can lead to loss of tissue, limbs or life. Antibacterial agents have been introduced into wound infection care. In this review, we provide an insight into the current antibacterial strategies of wound dressings, including wound infection process, antibacterial agents, and controlled drug release systems. We also emphasize the development of intelligent wound dressing and introduce a promising research direction.

The bacterial luciferase gene cassette (lux) is an ideal bioreporter for real-time monitoring of the dynamics of bacteria because it is a fully autonomous, substrate-free bioluminescent reporter system available in a prokaryotic or eukaryotic host background. The lux operon is emerging as a powerful bioreporter for the study of a wide range of biological processes such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis and cancer treatment. Furthermore, the use of a high signal to noise bioluminescent bioreporter is quickly replacing traditional fluorescent bioreporter because of the lack of endogenous bioluminescent reactions in living animals. This review briefly describes how the lux operon is used for bioluminescence imaging. Current advances in bioluminescence bacteria development are summarized, focusing on their construction strategy and applications in bacterial infection and antibiotic treatment. Different construction methods of lux-expressing cell lines are also discussed. Taken together, this review provides valuable guidelines toward the development of an ideal bioluminescent bacteria or cell lines to evaluate the efficacy of a drug.