Current Protein and Peptide Science - Volume 21, Issue 4, 2020

Therapeutic peptides (TPs) are biological macromolecules which can act as neurotransmitters, hormones, ion channel ligands and growth factors. Undoubtedly, TPs are crucial in modern medicine. But low bio-stability and some special adverse reactions reduce their places to the application. With the development of nanotechnology, nanoparticles (NPs) in pharmaceutical science gained much attention. They can encapsulate the TPs into their membrane or shell. Therefore, they can protect the TPs against degradation and then increase the bioavailability, which was thought to be the biggest advantage of them. Additionally, targeting was also studied to improve the effect of TPs. However, there were some drawbacks of nano TPs like low loading efficiency and difficulty to manufacture. Nowadays, lots of studies focused on improving effect of TPs by preparing nanoparticles. In this review, we presented a brief analysis of peptide-combined nanoparticles. Their advantages and disadvantages were listed in terms of mechanism. And several examples of applications were summarized.

In the rapidly evolving field of nanotechnology, plant virus nanoparticles (pVNPs) are emerging as powerful tools in diverse applications ranging from biomedicine to materials science. The proteinaceous structure of plant viruses allows the capsid structure to be modified by genetic engineering and/or chemical conjugation with nanoscale precision. This means that pVNPs can be engineered to display peptides and proteins on their external surface, including immunodominant peptides derived from pathogens allowing pVNPs to be used for active immunization. In this context, pVNPs are safer than VNPs derived from mammalian viruses because there is no risk of infection or reversion to pathogenicity. Furthermore, pVNPs can be produced rapidly and inexpensively in natural host plants or heterologous production platforms. In this review, we discuss the use of pVNPs for the delivery of peptide antigens to the host immune in pre-clinical studies with the final aim of promoting systemic immunity against the corresponding pathogens. Furthermore, we described the versatility of plant viruses, with innate immunostimulatory properties, in providing a huge natural resource of carriers that can be used to develop the next generation of sustainable vaccines.

Contact lens wear is generally safe and provides excellent vision. However, contact lens wear is often associated with the risk of developing ocular surface infection and inflammation, and in severe cases, the infection can result in loss of vision. Antimicrobial peptide-coated contact lenses have been made to help reduce the incidence of infection and inflammation. This paper reviews the research progress from conception, through the laboratory and preclinical tests to the latest information on clinical testing of an antimicrobial contact lens. We provide insights into the pathways followed and pitfalls that have been encountered. The journey has not always been linear or smooth, but has resulted in some of the first published clinical testing of antimicrobial peptide-coated contact lenses in humans. We hope this may help lead to the development and commercialisation of antimicrobial contact lenses in the future.

Host defense peptides (HDP) are small cationic molecules released by the immune systems of the body, having multidimensional properties including anti-inflammatory, anticancer, antimicrobial and immune-modulatory activity. These molecules gained importance due to their broad-spectrum pharmacological activities, and hence being actively investigated. Presently, respiratory infections represent a major global health problem, and HDP has an enormous potential to be used as an alternative therapeutics against respiratory infections and related inflammatory ailments. Because of their short half-life, protease sensitivity, poor pharmacokinetics, and first-pass metabolism, it is challenging to deliver HDP as such inside the physiological system in a controlled way by conventional delivery systems. Many HDPs are efficacious only at practically high molar-concentrations, which is not convincing for the development of drug regimen due to their intrinsic detrimental effects. To avail the efficacy of HDP in pulmonary diseases, it is essential to deliver an appropriate payload into the targeted site of lungs. Inhalable HDP can be a potentially suitable alternative for various lung disorders including tuberculosis, Cystic fibrosis, Pneumonia, Lung cancer, and others as they are active against resistant microbes and cells and exhibit improved targeting with reduced adverse effects. In this review, we give an overview of the pharmacological efficacy of HDP and deliberate strategies for designing inhalable formulations for enhanced activity and issues related to their clinical implications.

Nano-inspired technologies offer unique opportunities to treat numerous diseases by using therapeutic peptides. Therapeutic peptides have attractive pharmacological profiles and can be manufactured at relatively low costs. The major advantages of using a nanodelivery approach comprises significantly lower required dosages compared to systemic delivery, and thus reduced toxicity and immunogenicity. The combination of therapeutic peptides with delivery peptides and nanoparticles or small molecule drugs offers systemic treatment approaches, instead of aiming for single biological targets or pathways. This review article discusses exemplary state-of-the-art nanosized delivery systems for therapeutic peptides and antibodies, as well as their biochemical and biophysical foundations and emphasizes still remaining challenges. The competition between using different nanoplatforms, such as liposome-, hydrogel-, polymer-, silica nanosphere-, or nanosponge-based delivery systems is still “on” and no clear frontrunner has emerged to date.

Self-assembled peptides have been shown to form well-defined nanostructures which display outstanding characteristics for many biomedical applications and especially in controlled drug delivery. Such biomaterials are becoming increasingly popular due to routine, standardized methods of synthesis, high biocompatibility, biodegradability and ease of upscale. Moreover, one can modify the structure at the molecular level to form various nanostructures with a wide range of applications in the field of medicine. Through environmental modifications such as changes in pH and ionic strength and the introduction of enzymes or light, it is possible to trigger self-assembly and design a host of different self-assembled nanostructures. The resulting nanostructures include nanotubes, nanofibers, hydrogels and nanovesicles which all display a diverse range of physico-chemical and mechanical properties. Depending on their design, peptide self-assembling nanostructures can be manufactured with improved biocompatibility and in vivo stability and the ability to encapsulate drugs with the capacity for sustained drug delivery. These molecules can act as carriers for drug molecules to ferry cargo intracellularly and respond to stimuli changes for both hydrophilic and hydrophobic drugs. This review explores the types of self-assembling nanostructures, the effects of external stimuli on and the mechanisms behind the assembly process, and applications for such technology in drug delivery.

The emergence of multidrug-resistant pathogens and their rapid adaptation against new antibiotics is a major challenge for scientists and medical professionals. Different approaches have been taken to combat this problem, which includes rationally designed potent antimicrobial peptides (AMPs) and several nanoparticles and quantum dots. AMPs are considered as a new generation of super antibiotics that hold enormous potential to fight against bacterial resistance by the rapidly killing planktonic as well as their biofilm form while keeping low toxicity profile against eukaryotic cells. Various nanoparticles and quantum dots have proved their effectiveness against a vast array of infections and diseases. Conjugation and functionalization of nanoparticles with potentially active antimicrobial peptides have added advantages that widen their applications in the field of drug discovery as well as delivery system including imaging and diagnostics. This article reviews the current progress and implementation of different nanoparticles and quantum dots conjugated antimicrobial peptides in terms of bio-stability, drug delivery, and therapeutic applications.

Cationic antimicrobial peptides (AMPs) are an interesting class of gene-encoded molecules endowed with a broad-spectrum of anti-infective activity and immunomodulatory properties. They represent promising candidates for the development of new antibiotics, mainly due to their membraneperturbing mechanism of action that very rarely induces microbial resistance. However, bringing AMPs into the clinical field is hampered by some intrinsic limitations, encompassing low peptide bioavailability at the target site and high peptide susceptibility to proteolytic degradation. In this regard, nanotechnologies represent an innovative strategy to circumvent these issues. According to the literature, a large variety of nanoparticulate systems have been employed for drug-delivery, bioimaging, biosensors or nanoantibiotics. The possibility of conjugating different types of molecules, including AMPs, to these systems, allows the production of nanoformulations able to enhance the biological profile of the compound while reducing its cytotoxicity and prolonging its residence time. In this minireview, inorganic gold nanoparticles (NPs) and biodegradable polymeric NPs made of poly(lactide-coglycolide) are described with particular emphasis on examples of the conjugation of AMPs to them, to highlight the great potential of such nanoformulations as alternative antimicrobials.