ABSTRACT Poly(salicylic acid) (PSA) compounds, as representative examples of “carrier‐drug integrated” materials, effectively overcome issues such as low bioavailability, short half‐life, and systemic toxicity associated with the small‐molecule form of salicylic acid (SA) by incorporating this traditional drug molecule into the polymer backbone or side chains. This paper provided a systematic review of PSA synthesis strategies, including self‐polymerization, copolymerization, and grafting onto polymer backbones, with a focus on its extensive applications in the biomedical field. PSA materials demonstrated exceptional performance in antibacterial, anti‐inflammatory, and anticancer applications. Through mechanisms such as smart‐response release, targeted delivery, and synergistic therapy, they enabled precise intervention against diseases including infections, inflammation, and tumors. Furthermore, PSA has demonstrated significant potential in applications such as cardiovascular disease treatment, bone repair, and diabetic wound healing. Despite notable achievements in functional design and clinical application of PSA materials, their clinical translation still faces challenges including in vivo behavior studies, large‐scale synthesis, and multi‐response system design. Future research will focus on developing intelligent PSA materials, advancing their application in areas such as integrated diagnosis and treatment, and immunotherapy.

Polybetaines, as a class of zwitterionic polymers, are endowed with excellent protein adsorption resistance, outstanding biocompatibility, extremely low immunogenicity, and flexible stimuli-responsive behavior (e.g., to pH, temperature, ionic strength) due to their unique structure, Therefore, polybetaines demonstrate significant advantages in drug delivery systems. They can prolong the in vivo circulation time of drugs, enhance the accumulation at target sites, achieve intelligent responsive release, and finally improve drug efficacy and reduce side effects. This review systematically summarizes the molecular design, property regulation, and application progress of polybetaines in drug delivery. Firstly, the molecular design strategies are elaborated from two dimensions: monomer structures (carboxybetaine, sulfobetaine, phosphocholine) and polymerization methods (homopolymerization, random copolymerization, block copolymerization, graft copolymerization), thereby revealing the regulatory mechanisms underlying their anti-protein adsorption, biocompatibility, and environment-responsive behaviors. Subsequently, this review focuses on recent progress and potential of polybetaine carriers in chemotherapy drug delivery, gene delivery, and oral delivery of proteins and peptides. Finally, a brief commentary and outlook on the challenges and future developments of polybetaines are provided.

Diabetes mellitus (DM), a prevalent chronic metabolic disorder with a global prevalence over 10.5%, features persistent hyperglycemia-induced micro-/macro-vascular lesions and severe complications. Conventional DM management suffers from high risks of cross-infection or hypoglycemia, poor compliance, and failure to address the multi-faceted needs of integrated diagnosis and nonspecific treatment for complications. Microneedles (MNs), a minimally invasive platform that painlessly penetrates the stratum corneum to access interstitial fluid (ISF) or deliver therapeutics, has emerged as a transformative solution for DM care. Despite significant progress in developing MN-based systems for glucose monitoring, insulin delivery, and treatment of complications, challenges remain in achieving precise drug release, high loading capacity, long-term stability, and clinical translation. This review comprehensively summarizes the latest advances in MN-based platforms for DM management, covering three major glucose detection modalities with improved sensitivity and portability, gastrointestinal and glucose-responsive transdermal MNs for insulin delivery, fully integrated close-loop MN platforms, and MN applications in diabetic wound healing and other complications (ketoacidosis diagnosis, vascular disorders, neuropathy, depression). By addressing the critical gaps in scattered research, this work holds great significance for advancing minimally invasive, integrated, and patient-centered treatment models, ultimately improving the prognosis and quality of life for DM patients worldwide.

Accurately and efficiently assessing drug permeability has emerged as a critical challenge in early drug discovery and development, prompting the development of various models. In this study, a polymer planar biomimetic membrane permeation assay (PPBMPA) model was established using a Transwell chamber, and its permeability assessment capability was evaluated using model drugs with high, medium, and low permeability. The underlying permeation mechanism was also investigated. The results demonstrated that the biomimetic membrane spontaneously differentiated into an intestinal-like structure comprising a hydrated layer, a polymersome layer, and a basal layer, thereby mimicking the sequential process of drug permeation across the mucus layer, intestinal epithelium, interstitial space, and into the bloodstream. This highly biomimetic permeation pattern enabled effective differentiation between high and low absorption drugs, exhibiting a strong correlation with Caco-2 permeability (R2 = 0.85). Collectively, these findings suggest that the novel PPBMPA model holds promise as a reliable tool for rapid and reproducible drug permeability prediction.

Chronic wound infections in diabetes present significant clinical challenges due to their complex pathological microenvironment. Intelligent hydrogel dressings, with their three-dimensional network structure and high designability of functions, provide an innovative solution for diabetic wound management. This review systematically elaborates on the latest research progress of antibacterial hydrogels. Firstly, it outlines the pathological basis of diabetic wounds, then focuses on discussing natural polymers, synthetic polymers, and further analyzes the evolutionary context of composite intelligent hydrogels-specifically the systematic treatment strategies ranging from stimulus responsiveness, temporal control to multi-functional synergy-while emphasizing the design for their clinical applicability. Furthermore, it summarizes the comprehensive advantages of such dressings in infection control, immune regulation, and promotion of tissue regeneration, and discusses the potential challenges and prospects in the future, thereby providing certain references for the research and development of the next-generation intelligent dressings.

Diabetes is a highly prevalent chronic disease worldwide. Traditional insulin injection is inconvenient, driving oral insulin as a promising research area. However, oral insulin delivery encounters multiple physiological barriers in the gastrointestinal tract. As an indispensable organ for glucose metabolism, the liver serves as one of the key targets for insulin to exert its hypoglycemic effects. Thus, the development of liver-targeted delivery systems provides a novel strategy for improving insulin efficacy and reducing side effects. This technology is expected to promote the preferential utilization of insulin in the liver by mimicking physiological insulin secretion patterns, thereby effectively enhancing hypoglycemic effects while lowering the risk of hypoglycemia. This article reviewed the research progress in oral liver-targeted insulin delivery and its application in the treatment of diabetes and related complications, highlighting active and passive liver-targeting strategies. Passive liver targeting mainly relies on the synergy between the physicochemical properties of nanocarriers and the unique anatomical characteristics of the liver, achieving non-specific accumulation of insulin in hepatocytes. In contrast, active liver targeting is accomplished by modifying specific ligands on the carrier surface, which mediate receptor-mediated endocytosis via specific recognition and binding between ligands and receptors on the hepatocyte surface, thereby enabling precise enrichment of insulin in targeted hepatocytes. The advantages and application prospects of these two targeting strategies were analyzed to provide a theoretical basis for the research and development of oral insulin formulations, facilitate their clinical translation, and offer more effective and convenient therapies for diabetic patients.

Soluble epoxide hydrolase (sEH) plays a central role in regulating the metabolism of epoxyeicosatrienoic acids (EETs) and governs multiple pathophysiological cascades, establishing it as a key therapeutic target for metabolic, cardiovascular, cerebrovascular, inflammatory and pain-related disorders. Although several potent sEH inhibitors have advanced to clinical evaluation, classical single-target agents exhibit limited efficacy and a propensity for resistance when confronted with the multifactorial pathogenic nature of complex diseases. In recent years, the emerging paradigm of multi-target drug discovery offers a route to surmount these limitations. By synergistically modulating interacting pathways, dual-target inhibitors can not only reinforce therapeutic efficacy and reduce risk of drug resistance, but also minimize off-target effects caused by excessive intervention of a single target. Accordingly, a growing body of evidence indicates that dual-target sEH inhibitors demonstrate superior in vivo efficacy and safety compared to single-target sEH inhibitors. This review systematically summarizes the current research progress in dual-target sEH inhibitors, and give a comprehensive analysis of the rational design, structure-activity relationship (SAR) optimization and translational prospects of dual-target sEH ligands. It is expected to provide a theoretical foundation and innovative directions for developing efficient and safe multi-target sEH therapeutic strategies.

Human induced pluripotent stem cells (hiPSCs), similar to embryonic stem cells, are a class of pluripotent stem cells with the potential to differentiate into various kinds of cells. Because the application of hiPSCs obtained by reprogramming patients' somatic cells in the treatment of brain diseases bypasses the ethical constraints on the use of embryonic stem cells and mitigates immune rejection, hiPSCs have profound clinical application prospects. In this review, we first summarized the differentiation methods of hiPSCs into different kinds of neurons, and secondly discussed the application of hiPSCs in several brain disease models, so as to provide a reference for the future application of hiPSCs in the studies and treatment of brain diseases.

OBJECTIVE:The purpose of this review is to elaborate current development and challenges of oral albumin nanoparticles, and realize their clinical application. SIGNIFICANCE:Albumin is an emerging protein nanocarrier with a high degree of versatility, safety, stability, modifiability. These characteristics endow albumin nanoparticles with considerable attention and unique roles in drug delivery. However, most albumin nanoparticles are administered intravenously instead of orally, although oral administration is the most popular and common drug delivery route. Oral administration of albumin nanoparticles is their inevitable tendency, but researches referred to this area are still in infancy. METHODS AND RESULTS:Given that, firstly, the basic properties of albumin nanoparticles, like preparation methods, drug loading strategies, targeted drug delivery, and clinical application were simply discussed to provide design guide for their oral administration. Subsequently, the functions and challenges of albumin nanoparticles in oral drug delivery, and strategies to overcome the barriers were highlighted. Finally, aiming to realize their clinical potentials, the possible future trends of orally administrated albumin nanoparticles were also elaborated. CONCLUSIONS:In this review, albumin nanoparticles were comprehensively introduced, especially their functions and challenges in oral drug delivery, aiming to guide their design and development.

In order to detemine the anti-diabetic effect and potential mechanism of a novel soluble epoxide hydrolas inhibitor(A34)on diabetic mice.Type 1 diabetes mellitus(T1DM)mice were induced by streptozotocin(50 mg/(kg·d)for 5 days,ip.)and the hypoglycemic effect of A34 were evaluated by water and food intake,non-fasting and fasting blood glucose,glucose tolerance and plasma insulin level in diabetic mice after water administration.The underlying mechanism was explored via measuring the expression level of sEH in islets,the morphological change of islets and the concerntration of cytokines INF-γ and IL-4 in plasma.Compared with diabetic model group,the water and food intake(p<0.01,p<0.05),blood glucose(p<0.01),glucose tolerance(p<0.01)and plasma insulin level(p<0.05)were improved in A34 group.Additionally,A34 could protect pancreatic islet morphology,suppress sEH expression in islet(p<0.01),reduce the ratio of INF-γ to IL-4 in plasma(p<0.05).These results showed that A34 prevents hyperglycemia and β-cell dysfunction through regulating the dynamic balance of pro-inflammatory and anti-inflammatory cytokines in diabetic mice.

The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases. EpFAs play a protective role in the central nervous system via preventing neuroinflammation, making sEH a potential therapeutic target for CNS diseases. Recent studies showed that sEH inhibition prevented BBB impairment caused by stroke, hemorrhage, traumatic brain injury, hyperglycemia and sepsis via regulating the expression of tight junctions. In this review, the protective actions of sEH inhibition on BBB and potential mechanisms are summarized, and some important questions that remain to be resolved are also addressed.

Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications. Herein, we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code. In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins. Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment, without urea and after QTY modification. Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins. Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly, hemostasis, and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.

Ischaemic stroke is a central nervous system disease with high morbidity, recurrence and mortality rates. Thrombolytic and neuroprotective therapies are the main therapeutic strategies for ischaemic stroke, however, the poor delivery efficiency of thrombolytic and neuroprotective drugs to the brain limits their clinical application. So far, the development of nanomedicine has brought opportunities for the above challenges, which can not only realise the effective accumulation of drugs in the target site, but also improve the pharmacokinetic behaviour of the drugs. Among the most rapidly developing nanoparticles, micelles gradually emerging as an effective strategy for ischaemic stroke treatment due to their own unique advantages. This review provided an overview of targeted and response-release micelles based on the physicochemical properties of the ischaemic stroke microenvironment, summarised the targeting strategies for delivering micellar formulations to the thrombus, blood-brain barrier, and brain parenchyma, and finally described the potentials and challenges of polymeric micelles in the treatment of ischaemic stroke.

与原代神经元相比,器官型海马脑片神经元之间可保持正常的突触回路和生理形态学特征,相对于体内模式改变较小,是研究中枢神经系统疾病的良好样本.近年来,随着脑片培养技术及检测方法的不断提高,脑片存活时间大大延长,检测手段更加多样化,器官型海马脑片培养技术在生物医药领域的应用范围不断扩大.本文对器官型海马脑片的培养方法、制备过程、培养环境等关键影响因素进行了综述,旨在为优化器官型海马脑片的培养方案提供支持.

目的 建立一种简单易行的高纯度原代皮质神经元长期培养方法.方法 取胎龄为16～18 d的SD胎鼠,分离皮质并剪碎,经胰酶消化、吹打、计数后,接种于PDL包被的培养板上,6 h后换为维持培养基进行培养,每5d半量换液,培养至第7,14和21d时,采用NSE和GFAP荧光染色鉴定神经元纯度.实验过程中主要摸索了以下几个条件:胰酶溶液、细胞接种密度、维持培养基和胶质细胞增殖抑制剂添加时间.结果 优化后的神经元培养条件为:使用含EDTA的0.0625%胰蛋白酶进行消化;以40000 cm-2密度接种;以Neurobasal Plus培养基作为维持培养基;培养至第6小时到第5天时,给予10 μmol·L-1 5-氟尿嘧啶和尿嘧啶.采用上述条件培养的神经元可以达到在体外健康生长至3周以上,纯度＞90%.结论 本文以SD胎鼠皮质为样本建立了简便的高质量神经元长期培养方法.

因与谷氨酸AMPA受体和NMDA受体具有高度的序列相似性,谷氨酸GluD受体被归类为离子型谷氨酸受体,但由于GluD受体的结构特征不同于其他离子型谷氨酸受体,无法自发形成离子通道,不通过介导离子流动传递信号.近期的研究表明,GluD受体与精神分裂症、双相情感障碍、自闭症谱系障碍、可卡因成瘾、小脑萎缩、小脑共济失调等多种中枢神经系统疾病有紧密关联.本文将对GluD受体的结构特征、信号转导方式以及在多种脑部疾病中的病理生理作用作一综述,为开发基于GluD受体的脑部疾病治疗新策略提供思路.

人诱导多潜能干细胞(hiPSC)是一类与胚胎干细胞类似、具有分化成各种细胞潜能的多能干细胞.将患者体细胞重编程得到的hiPSC应用于脑部疾病的治疗,绕开了使用胚胎干细胞的伦理限制,减轻了免疫排斥反应,具有远大的临床应用前景.本文首先描述了hiPSC定向分化为多巴胺能、谷氨酸能、γ-氨基丁酸能和乙酰胆碱能等多种神经元及神经胶质细胞的方法,其次对hiPSC在阿尔茨海默病、帕金森病和运动神经元病等脑部疾病的模型建立、个性化治疗和组织再生疗法中的应用现状进行综述,为将来hiPSC应用于这些疾病提供参考.

Autogenous keratin is a promising material for personalized wound healing applications. However, the common keratin extraction methods are time-consuming, and the variations in performance between different individual keratins are not clear. Herein, we developed TiO2 photocatalytic-assisted H2O2 oxidation strategy (H2O2/TiO2/UV), an advanced oxidation method, to rapidly extract human hair keratins within 2 h. The H2O2/TiO2/UV method for keratin extraction showed a higher protein yield compared to the H2O2 method. Keratins obtained from the developed method exhibited typical chemical and secondary structures. Furthermore, individual keratins from four young girls were extracted by using the H2O2/TiO2/UV method, and individual keratin/PCL films were successfully fabricated within 5 h. More importantly, individual keratin films displayed superior hemostatic performance and wound healing in vivo compared to that of keratin extracted via the H2O2 method. Interestingly, the four individual keratin films exhibited similar hemostatic efficiency but distinct wound-healing properties in terms of epidermal thickness and density of skin appendages. These data indicated that the developed H2O2/TiO2/UV method is an efficient and feasible approach to extract human hair keratins, which provides an intriguing possibility to explore personalized materials for promoting wound healing.