Drug delivery is a method or process for achieving therapeutic effects in humans or animals by using specific means to effectively deliver active pharmaceutical ingredients to target sites. The delivery systems play important roles in controlling the speed of drug release, targeting drug delivery to the site, maintaining drug stability and biocompatibility. In recent years, with the advancements of related fields such as pharmaceutical science, material science, and biomedicine, the development of technologies from nanoscale to cell scale and smart targeted drug delivery has brought tremendous changes in the field of drug delivery systems, The research investment and market share of drug delivery systems continue to grow rapidly. This paper elaborated the delivery mechanism and characteristics of different drug delivery systems, systematically analyzed the main research progresses and enterprise competition pattern of new drug delivery system technologies, and discussed the clinical transformation potential and application prospects of related technologies, in order to provide references for the choice of R&D direction selection and decision-making of related companies.
The strong hydrophobicity, low stability and high side effects of drugs largely limit their clinical use. Drug delivery system (DDS) has undergone fast growth. It can effectively carry and protect drugs, thus increasing their biocompatibility, action specificity and effectiveness. Hydrophobins are small molecular proteins secreted during the special period of fungi, such as the development of fungal fruiting bodies. They possess unique amphiphilicity to aid their self-assembly into micellar structure and modification for other DDSs progress, while their extremely low immunogenicity and cytotoxicity further support their application in drug delivery. This paper reviews the research progress of hydrophobin-based DDS in recent years.
Milk exosomes are ubiquitously extracellular vesicles in mammalian milk that are rich in bioactive molecules and transfer the contents to recipient cells. Due to their latent drug delivery potential and great clinical application prospects, milk exosomes have gradually attracted extensive attention of researchers in recent years. However, there are still some problems between the laboratory and clinical translation, including the yield of milk exosomes, heterogeneity of isolation, purification methods, and loading efficiency. This paper systematically summarizes the current research in terms of the composition, physicochemical properties, separation and purification, drug loading and targeted delivery of milk exosomes, and finds out the weak links in the existing research, so as to provide a theoretical support for the transformation from experimental stage to clinical treatment stage.
Subcutaneous insulin is the most effective way to control blood sugar levels and plays a crucial role in the treatment of patients with type I and advanced type II diabetes. However, frequent subcutaneous injections bring great pain to patients, so for the treatment of diabetes, oral therapy is preferred at present. Oral insulin can mimic physiological insulin secretion and provide more comprehensive regulation of hepatic glucose metabolism, but the development of oral insulin administration is greatly hampered by gastrointestinal malabsorption. The rapid development nanoscale drug delivery systems (NDDS) of has increased the possibility of oral insulin. Polymeric nanomaterials are important carrier materials in NDDS, which have been widely used to promote oral insulin absorption. They have the advantages of biodegradability, biocompatibility and storage stability, and their molecular chain is long and the structure is easy to be changed, modified and processed. The polymeric nanomaterials can protect the encapsulated insulin from the effects of acid denaturation and enzymatic degradation, promote the uptake of insulin by cells, and thus improve the bioavailability of insulin. This review discusses the main physiological obstacles to oral insulin and summarizes the research progress of polymer nanomaterials for oral insulin delivery in recent years.
Diabetic ulcer is one of the most serious complications of diabetes mellitus. It has the characteristics of long healing cycle, difficulty in cure and high recurrence rate. Dressing as an important part of the treatment of diabetic ulcers cannot be ignored. Ideal wound dressings should have characteristics of hemostasis, antibacterial property and high biocompatibility, while traditional dressings are far from meeting the needs of diabetic wounds. With the development of nanotechnology, nanofiber dressings prepared by electrospinning technology have made some progress in the treatment of diabetic ulcers. Therefore, based on the understanding of the refractory mechanism of diabetic ulcers, the matrix materials, loading materials and research status of electrospun nanofiber dressings were reviewed, so as to provide reference for further research.
Objective: Proteomic technique was used to study the differentially expressed proteins in the cervical spinal cord of guinea pigs subacutely exposed to soman, to explore the main biological pathways affected by soman poisoning, and to provide important biomarkers for the diagnosis, treatment, and prognosis of soman poisoning. Methods: Soman (0.2×LD50) was subcutaneously injected into the back of male adult guinea pigs once a day for 14 consecutive days for subacute exposure. The cervical spinal cord tissue was collected after the final exposure, and the differentially expressed proteins between the soman and control group were analyzed by proteomics technology. Functional annotation and pathway enrichment analysis of differentially expressed proteins was performanced using KEGG database. The function of differential proteins in important pathways was analyzed and discussed. Results: A total of 3 563 proteins annotated by KEGG database were identified in cervical spinal cord tissues of guinea pigs. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed that there were 407 differentially expressed proteins after exposure to soman, of which 276 proteins were up-regulated and 131 were down-regulated. These differential proteins are mainly related to metabolism (M), genetic information processing (GIP), environmental information processing (EIP), cellular processes (CP), organismal systems (OS), and human diseases (HD). The up-regulated proteins are mainly enriched in 27 pathways (P<0.05), and the down-regulated proteins are mainly enriched in 8 pathways (P<0.05). The main enrichment pathways of up-regulated proteins include phagosome pathway, tight junction pathway, extracellular matrix (ECM)-receptor interaction pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, complement and coagulation cascade pathway, which are related to up regulation of 24 protein expressions. Conclusion: Based on proteomics research, it was clarified that a large number of differentially expressed proteins appeared in the cervical spinal cord of guinea pigs subacutely exposed to soman, and the six main pathways were helpful to further elucidate the non-cholinergic mechanism of subacute injury. The differential expressed proteins could provide important biomarkers for the diagnosis, treatment, and prognosis of poisoning, as well as important theoretical basis for the development of new antitoxic drugs.
Objective: To investigate the synergistic regulation of carbon and nitrogen sources on the cell growth and spore generation of Bacillus licheniformis BF-002, so as to increase the number of living cells and spores in fermentation broth. Methods: Under the scale of 5 L fermentor, the effects of nitrogen source concentration and carbon source concentration on cell growth and spore formation were investigated, and the method of starting spore formation and promoting the continuous and efficient transformation of vegetative cells into spores by adjusting carbon source concentration was established. Finally, the carbon source/nitrogen source synergistic feeding control strategy was established to improve the production of living cells and spores at the end of fermentation. The results showed that spore generation could be initiated when the concentration of carbon source decreased to the critical level (about 0.5 g/L) or when the concentration of carbon source decreased to the critical level (about 2.0 g/L). The concentrations of glucose and amino nitrogen were controlled at 10 g/L and 1.5 g/L, respectively before 24 h, and maintained at 2 g/L and 0.5 g/L after 24 h for 48 h. The number of living cells and spores reached 2.88×1010 CFU/mL and 2.56×1010 CFU/mL, respectively. Compared with the optimal batch with glucose concentration controlled alone, the number of spores increased 2.91 times. Conclusion: When the concentration of carbon source and nitrogen source in logarithmic growth period is controlled at an appropriate level, a higher amount of living cells can be obtained. Subsequently, by reducing the concentration of carbon source and nitrogen source and keeping them at their respective critical levels, we can promote the continuous and efficient transformation of vegetative cells into spores.
Biocatalyst enzymes are sensitive to the environment, and high temperature has a significant effect on enzyme inactivation among various physical, chemical and biological factors. The construction of heat-resistant specific matrix and the immobilization of the enzyme can not only improve the stability of the enzyme at high temperature, but also realize the reuse of the catalyst, which greatly improves the industrial application value of the enzyme. In this study, chitosan hydrogels with excellent mechanical properties and high temperature resistance were prepared by means of dissolution and hydrogen bond rearrangement of alkaline solution under freezing conditions, and the immobilized high temperature resistant enzyme was further prepared by chemical cross-linking. The optimal conditions for the fixation of high temperature resistant enzyme were determined by single factor experiment: the mass fraction of chitosan was 5%, the mass fraction of sodium alginate was 0.5%, the mass concentration of ZnSO4 solution was 20 g/L, and the volume fraction of EGDE was 0.8%. Compared with the free enzyme, the immobilized enzyme showed improved acid-base resistance and thermal stability, optimum temperature increase of 5℃ (from 90℃ to 95℃), and also maintained high activity over a wide range of pH and temperature. At the temperature of 80℃, the relative enzyme activity remained above 75% after 8 repeated reactions. Thermogravimetric analysis (TGA) was used to study the state and thermal stability of water in the hydrogels. The immobilized enzyme preparation method established in this study is helpful to solve the problem that industrial enzymes are easy to be inactivated at high temperature and difficult to be used continuously.
In order to maintain normal physiological activities, cells have evolved a membrane system, which enables various activities to occur efficiently and in an orderly manner in a specific space and time. The involvement of membrane system in material transport, signal transmission, energy metabolism and other processes has been widely understood, but the molecular details related to the assembly and function of membrane-free compartments have not been thoroughly studied. Biological macromolecules form a variety of membrane-free compartments in cells through phase separation, such as nucleolus, centrosome, and stress particles, which are collectively referred to as biomolecular condensates. As a mechanism of aggregation and separation of cellular biochemical reactions, phase separation is ubiquitous in nature and widely involved in many important physiological processes such as signal transduction and gene transcription regulation. The abnormal phase separation is closely related to many human diseases, such as neurodegenerative diseases, cancer and infectious diseases. By introducing the cellular structure and function of phase separation and its mechanism, this paper will further elaborate the role of phase separation in the occurrence and development of diseases.
Angiomotin(AMOT) is a type of angiogenesis inhibitor binding protein. Members of the AMOT family (AMOTs) are involved in various critical biological processes, for example, cell proliferation, cell migration, angiogenesis, and virus release. AMOTs expressed in most cancer and regulate cancer development and progression. Available evidence suggests that AMOTs act as both tumor promoters and tumor suppressors, and this opposite regulation in cancer still needs to be validated. This review focuses on the structure, expression localization, and function of AMOTs, and additionally, it systematically summarizes previous research and therapeutic roles in cancer. It discusses the possibility and challenges of treating cancer through AMOTs.
Macrophage migration inhibitory factor (MIF) is a widely expressed pleiotropic cytokine that controls various biological functions of cells, including cell proliferation, differentiation, survival and apoptosis. Recent studies have found that MIF is closely associated with cell senescence, suggesting that MIF may regulate cell senescence. To further understand the mechanism of cell senescence, the role of MIF in cell senescence and its mechanism in recent studies was summarized in this article, which includes how MIF controls senescence related gene expression, especially in hypoxia and oxidative stress conditions. The complex regulatory mechanisms of aging related diseases in the context of MIF functional polymorphism were further analyzed. Finally, the development and application of bioengineering products of MIF and its receptors were introduced. It lays a foundation for further study on the mechanism of MIF regulating cell senescence.
BAK protein, a member of the BCL-2 family, is a key protein in the apoptosis pathway. It is activated under the stimulation of apoptotic signals, and after clustering on mitochondria, induces the release of cytochrome c and other pro-apoptotic substances, amplifies apoptosis signals through caspase cascade reaction, and finally promotes cell death. At present, the role of BAK in the apoptosis escape of cancer cells and the activation of intracellular inflammatory response has been confirmed, but the mechanism of action between viruses and other pathogens and BAK, the activation process of intracellular apoptosis and inflammatory pathways are less studied. Therefore, in this paper, the structure and function of BAK protein and the related pathways mediated by BAK are introduced, and the progress of its role in the study of virus infection is analyzed, in order to provide some theoretical basis for the in-depth study of the pro-apoptotic protein BAK in virus infection.
Based on the principle of modular linear synthesis of peptides by non-ribosomal peptide synthetases (NRPS), it has become a research hotspot to engineer and recombine its catalytic module and design the biosynthetic pathway of peptides to obtain the target peptides. However, heterozygous NRPS has many problems. For example, the catalytic module cannot load the target amino acids or the synthesis efficiency of peptides is significantly reduced, which limits its application. In recent years, great breakthroughs have been made in the research of substrate selectivity of NRPS adenylation domain (A domain) and condensation domain (C domain), docking domain (DD) between NRPS subunits and linker between modules. This review introduces the research progress of NRPS catalytic module reconsitution from the two aspects of substrate selectivity in C domain and catalytic unit substitution with different fusion boundaries, and summarizes the advantages and limitations of each substitution scheme.
Polyhydroxyalkanoates(PHAs)as a kind of intracellular energy storage material with high biodegradability and easy processing, are expected to replace petroleum based plastics and have attracted more and more attention in the global bioplastics market. Lignin, as the most abundant natural renewable aromatic polymer on the earth, can be used as a substrate to be converted into monocyclic aromatic compounds such as phenol through microbial degradation, and then synthesize degradable plastic PHAs. In this paper, the microorganisms and related pathways of lignin degradation and transformation to synthesize PHAs are reviewed, and the existing problems and difficulties are described. The research progress on improving the survival efficiency and product performance of PHAs synthesized by lignin degradation and transformation was deeply discussed. At the same time, the challenges faced by the synthesis of PHAs by lignin transformation and the prospects for the future development were put forward.
Quorum sensing system was not just involved in interbacterial communication but also involved in communication between bacteria and their hosts. It has been demonstrated that the difference in quorum sensing system invoved in gram positive and gram negative bacteria was statistically significan. The quorum sensing system of positive bacteria has played important roles in many of the physiological characteristics such as pathogenicity, which was composed of oligopeptide signal molecules and receptor proteins. In this paper the current research status and advances in gene composition, signal molecular characteristics and regulation mechanisms of quorum sensing system involved in typical gram-positive bacteria, such as Bacillus cereus, Bacillus subtilis, Staphylococcus aureus and Streptococcus pneumoniae were summarized. The regulatory mechanisms of quorum sensing system invovled in important physiological activities of bacteria, such as nutrient absorption, biofilm formation, virulence factor production, spore production and cytidine production were illustrated. This study will provide a reference for the future research on quorum sensing of gram-positive bacteria.
In recent years, China’s research progress on real world study has received widespread attention, and the relevant regulatory policies and regulations are also modified and improved on a regular basis, but the relevant literature in the field of medical devices is rare. Starting from the policy background of domestic and foreign real world evidence for regulatory decision-making, this paper focuses on the key elements of real world evidence used to support medical device regulatory decisions in combination with the application of real world data in clinical evaluation of medical devices. It also discusses the opportunities and challenges, with a view to providing reference for promoting real world evidence used to support medical device regulatory decisions.
Active substances are often synthesized by microorganisms as carriers in biological metabolic engineering at all times, and the formation of metabolites in all stages of the life system provides a natural template and design blueprint for the development of synthetic biotechnology. If these metabolites involve harmful active substances or potential safety threats, such as toxins and protein complexes that are toxic to humans, animals and plants, drug molecules and their derivatives that can be used for clinical treatment and can also lead to dysfunction and health hazards, and chemicals that are prohibited or restricted by international conventions, they will have adverse effects on biosafety. Through reviewing and analyzing the safety risks in synthetic biology related to active substances such as natural metabolic pathway biosynthetic active substances, non-natural metabolic pathway biosynthetic active substances, chemosynthetic active substances and active substance delivery technology, this paper puts forward countermeasure strategy for promoting the innovative development and application fields of active substances in synthetic biology.
Targeted protein degradation technology breaks the limitations of traditional therapies and is considered to be a revolutionary technology in the field of biomedicine due to its high activity, high selectivity and targeting of “undruggable”targets. It has developed into one of the most cutting-edge and effective disease treatment strategies. In the past two decades, various degradation technologies based on targeted protein degradation systems have been emerging. Among them, small molecule targeted protein degradation drugs, represented by molecular glues and proteolysis-targeting chimeras, have made rapid progress. A large number of clinical trials and evaluations have fully confirmed the universality and effectiveness of targeted protein degradation. The technology brings new potential treatment options for some “incurable” diseases, and has great development and utilization value and market potential. In order to further promote the innovation and development of China’s targeted protein degradation drug industry, quantitative and qualitative combination of analytical methods are used in this paper to deeply analyze the current situation and market trends of technology and product research and development of targeted protein degradation drugs industry domestically and overseas. Meanwhile, targeted countermeasures are put forward from the perspective of future breakthrough direction and institutional mechanism innovation.
