Recent advances in the development of tumor microenvironment-activatable nanomotors for deep tumor penetration.

Cancer represents a significant threat to human health, with the use of traditional chemotherapy drugs being limited by their harsh side effects. Tumor-targeted nanocarriers have emerged as a promising solution to this problem, as they can deliver drugs directly to the tumor site, improving drug effectiveness and reducing adverse effects. However, the efficacy of most nanomedicines is hindered by poor penetration into solid tumors. Nanomotors, capable of converting various forms of energy into mechanical energy for self-propelled movement, offer a potential solution for enhancing drug delivery to deep tumor regions. External force-driven nanomotors, such as those powered by magnetic fields or ultrasound, provide precise control but often necessitate bulky and costly external equipment. Bio-driven nanomotors, propelled by sperm, macrophages, or bacteria, utilize biological molecules for self-propulsion and are well-suited to the physiological environment. However, they are constrained by limited lifespan, inadequate speed, and potential immune responses. To address these issues, nanomotors have been engineered to propel themselves forward by catalyzing intrinsic "fuel" in the tumor microenvironment. This mechanism facilitates their penetration through biological barriers, allowing them to reach deep tumor regions for targeted drug delivery. In this regard, this article provides a review of tumor microenvironment-activatable nanomotors (fueled by hydrogen peroxide, urea, arginine), and discusses their prospects and challenges in clinical translation, aiming to offer new insights for safe, efficient, and precise treatment in cancer therapy.

Senolytic Therapy Enabled by Senescent Cell-Sensitive Biomimetic Melanin Nano-Senolytics.

Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib and Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses a challenge in achieving optimal outcomes. Despite the recent occurrence of nanomaterial-based approaches targeting SnCs, limited therapeutic effects, and potential toxicity still remain a major concern. Herein, a "double locks-like" nanoplatform is developed that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ is only released in SnCs that are featured with higher levels of ß-galactosidase (ß-gal) and low PH. Additionally, the nanoparticles are equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrate remarkable specificity and efficacy in eradicating SnCs, and accordingly reverse pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrate to efficiently remove senescent tumor cells inducted by chemotherapy, thereby hindering the outgrowth and metastasis or breast cancer. Collectively, the present study develops an "On/Off" switchable nanoplatform in response to SnCs, and produces a more safe, efficient, and feasible way to delay aging or alleviate age-associated diseases.

A rare case of Baker's cysts with hematoma of the lower calf treated with arthroscopic internal drainage combined with intramuscular dissection.

Popliteal cysts, also termed Baker's cysts, are clinically common cystic lesions in the popliteal fossa. Typically, the contents of a ruptured cyst tend to spread into the myofascial interfaces in any direction, most commonly inferomedially or into a palpable superficial position. However, to our knowledge, reports of Baker's cysts dissecting into the deep intermuscular septum of the lower calf are extremely rare. We present here the details of the successful treatment through arthroscopy combined with lower calf incision of a patient who sustained hematoma of the knee and lower calf secondary to Baker's cyst rupture. Given the rarity of this disease in China, we present this case report to improve our understanding of the disease and avoid misdiagnosis and provide evidence for its clinical treatment, management, and prognosis.

Tibial tubercle avulsion fracture following preexisting Osgood-Schlatter disease in an adolescent: a case report.

Tibial tubercle avulsion fractures (TTAFs) are rare but typical in children and adolescents and Osgood-Schlatter disease (OSD) may be involved in their pathogenesis. However, few publications have reported the relationship between OSD and TTAF. A 16-year-old healthy male adolescent presented with pain, swelling and limited range of motion of the right knee following sudden acceleration while running. Based on the radiographic evidence, the patient was diagnosed with an avulsion fracture of the right tibial tubercle and OSD. Open reduction and internal fixation were performed using two cannulated screws and two Kirschner wires. The patient returned to preinjury activity levels at the 12-month follow-up postoperatively. This case report aimed to highlight this unique injury pattern. For patients with TTAFs, not only should the fracture be treated, but the cause of the fracture, such as OSD, should also be given appropriate treatment.

Study on the quality of Corydalis Rhizoma in Zhejiang based on multidimensional evaluation method.

ETHNOPHARMACOLOGICAL RELEVANCE: The quality requirements of Corydalis Rhizoma (CR) in different producing areas are uniform, resulting in uneven efficacy. As a genuine producing area, the effective quality control of CR in Zhejiang Province (ZJ) could provide a theoretical basis for the rational application of medicinal materials. AIM OF THE STUDY: The purpose of this study was to effectively distinguish the CR inside and outside ZJ, and provided a theoretical basis for the quality control and material basis research of ZJ CR. MATERIALS AND METHODS: The core components of ZJ CR could be identified by HPLC combined with chemometrics screening, and the quality of CR from different producing areas was evaluated by a genetic algorithm-back propagation (GA-BP) neural network. Chromaticity and near-infrared (NIR) spectroscopy were used to identify CR inside and outside ZJ, and rapid content prediction was realized. The analgesic effect of CR in different regions was compared by a zebrafish analgesic experiment. Analgesic experiments in rats and analysis of the research status of quality components were used to screen the quality control components of ZJ CR. RESULTS: The contents of palmatine hydrochloride (YSBMT), dehydrocorydaline (TQZJJ), tetrahydropalmatine (YHSYS), tetrahydroberberine (SQXBJ), corydaline (YHSJS), stylopine (SQHLJ), and isoimperatorin (YOQHS) in ZJ CR were higher than those in CR from outside ZJ, but the content of protopine (YAPJ) and berberine hydrochloride (YSXBJ) was lower than that in CR from outside ZJ. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. The GA-BP neural network showed that the relative importance of ZJ CR was the strongest. Chroma-content correlation analysis and the NIR qualitative model could effectively distinguish CR from inside and outside of ZJ, and the NIR quantitative model could quickly predict the content of CR from inside and outside of ZJ. Zebrafish experiments showed that ZJ, Shaanxi (SX), Henan (HN), and Sichuan (SC) CR had significant analgesic effects, while Hebei (HB) CR had no significant analgesic effect. Overall comparison, the analgesic effect of ZJ CR was better than that of CR outside ZJ. The comprehensive score of the grey correlation degree between YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, YHSJS, SQXBJ, and SQHLJ were higher than 0.9, and the research frequency were extremely high. CONCLUSIONS: The relative importance of the content and origin of most components of ZJ CR was higher than that of CR outside ZJ. The holistic analgesic effect of ZJ CR was better than that of CR outside ZJ, but slightly lower than that of SX CR. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, SQXBJ, YHSJS, and SQHLJ could be used as the quality control components of ZJ CR. The multidimensional evaluation method used in this study provided a reference for the quality control and material basis research of ZJ CR.

[Progress on study of factors influencing the prognosis and complications of surgery for discoid meniscus injury in children].

The discoid meniscus is a common congenital meniscal malformation that is prevalent mainly in Asians and often occurs in the lateral discoid meniscus. Patients with asymptomatic discoid meniscus are usually treated by conservative methods such as observation and injury avoidance, while patients with symptoms and tears need to be treated surgically. Arthroscopic saucerization combined with partial meniscectomy and meniscus repair is the most common surgical approach., and early to mid-term reports are good. The prognostic factors are the patient's age at surgery、follow-up time and type of surgery. Some patients experience complications such as prolonged postoperative knee pain, early osteoarthritis, retears and Osteochondritis dissecans. The incidence of prolonged postoperative knee pain was higher and the incidence of Osteochondritis dissecans was the lowest. Retears of the lateral meniscus is the main reason for reoperation.

Identifying influential financial stocks using simulation with a two-layer network.

Risk spillover from one stock to another tends to create a contagion effect in the stock market. Fire sales due to the overlapping portfolios of mutual funds can amplify the contagion risks, leading to a downward spiral of stock prices. In this paper, we simulate this downward spiral phenomenon for the Chinese financial stocks based on a two-layer network structure and aim to identify the influential financial stocks based on their individual induced systemic risks. Our findings show that stock liquidity and the concentration of funds' holding on stocks play important roles in determining systemically important financial institutions. Our results also confirm the statements of "too-big-to-fail" and "too-interconnected-to-fail" of financial institutions in the Chinese market. Our results show that a more sensitive flow-performance relationship of mutual funds can amplify the contagion risk by 41%. However, the magnitude can be more drastic in a low market liquidity scenario, where the contagion risk is boosted by 160%.

A global systematic review and meta-analysis of prevalence of repeat induced abortion and correlated risk factors.

As a significant public health problem, repeat-induced abortion is a challenge to women's sexual and reproductive health. Despite many studies in this area, they lack consensus regarding risk factors for repeat-induced abortion. A global systematic review was conducted to analyze prevalence of repeat-induced abortion among women worldwide and determine correlated risk factors. Three electronic databases were systematically searched. Data on prevalence of repeat-induced abortion and related factors were extracted and pooled using a meta-analysis and narrative approach. Sixty-five (which were published between 1972 and 2021) of 3,706 articles were included, consisting of a total of 535,308 participants from 25 countries. The overall pooled prevalence of repeat-induced abortion was 31.3 percent (95 percent CI 25.7 percent, 36.9 percent). Of 57 exposures extracted, 33 factors were significantly correlated with repeat induced abortion, comprising 14 individual demographic factors (i.e. age, education, marriage, etc.), three reproductive history-related factors (i.e. parity, age at sexual debut, and time since sexual debut), five contraception-related factors (i.e. contraceptive use at sexual debut, attitude toward contraceptive use, etc.), four abortion-related factors (i.e. age at the index abortion, previous abortion at the index abortion, etc.), and seven sexual partner-related factors (i.e. multiple sexual partners, sexual partner's age, etc.). The study findings highlight the problem of repeat-induced abortion worldwide and suggest the need for government and civil society in each country to increase efforts to reduce the alarming risk of repeat-induced abortion among women and improve their sexual and reproductive health.

lncRNA NEAT1/miR-495-3p regulates angiogenesis in burn sepsis through the TGF-ß1 and SMAD signaling pathways.

INTRODUCTION: To investigate the role of the long-chain noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in the process of angiogenesis in human umbilical vein endothelial cells (HUVECs) and illustrate its potential role in burn sepsis (BS) pathogenesis. METHODS: HUVECs were treated with BS patient serum or healthy control serum. NEAT1 shRNA, miR-495-3p mimics, and miR-495-3p inhibitor were transfected into HUVECs. NEAT1 and miR-495-3 levels in serum or HUVECs were detected using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 and flow cytometry assays were used to explore the proliferation and apoptosis of HUVECs. The expression of vascular endothelial growth factor (VEGF) in the supernatant was detected using enzyme-linked immunosorbent assay. Tube formation of HUVECs was also analyzed. Western blot analysis was used to analyze signaling pathway proteins. RESULTS: In HUVECs stimulated with BS patient serum, NEAT1 expression was increased, while miR-495-3p expression was decreased. In addition, NEAT1 silencing by specific shRNA inhibited cell proliferation, VEGF production, and tube formation under burn patient serum treatment, which decreased the TGFß1/SMAD signaling pathway activation. Moreover, miR-495-3p minics inhibited angiogenesis and the activation of signaling pathways induced by NEAT1 shRNA. Furthermore, miR-495-3p inhobitor promoted angiogenesis in HUVECs and activated the TGFß1/SMAD signaling pathway. In patients with BS, NEAT1 expression was significantly increased and miR-495-3p expression was decreased compared to healthy controls, and NEAT1 and miR-495-3p expression was associated with the clinical features of patients. CONCLUSIONS: Our results indicate that lncRNA NEAT1 regulates angiogenesis and activates the TGFß1/SMAD signaling pathway during the occurrence of BS.

Population genetic characteristics of Hainan medaka with whole-genome resequencing.

The DMY gene is deleted in all males of the Sanya population (SY-medaka) of the Hainan medaka, Oryzias curvinotus, as recently reported by us. However, due to limited knowledge regarding their population genetic background, it is difficult to explore the possible evolutionary pathway. Herein, we resequenced the whole genome of four populations, including SY-medaka. A total of 56 mitogenomes and 32,826,105 SNPs were identified. We found that the genetic differentiation is highest between SY-medaka and the other populations. The results of the population history of the O. curvinotus suggest that the SY-medaka has been in a bottleneck period recently. Further analysis shows that SY-medaka are the most strongly affected by environmental selection. Moreover, we screened some potential genomic regions, and the genes contained in these regions may explain the potential mechanism of the selection process of the SY-medaka. In conclusion, our study can provide new clues for the adaptation process of medaka in the new environment of Sanya.

Molecular Identification of Nocardia seriolae and Comparative Analysis of Spleen Transcriptomes of Hybrid Snakehead (Channa maculata Female × Channa argus Male) With Nocardiosis Disease.

Hybrid snakehead (Channa maculata female × Channa argus male) is a new freshwater aquaculture fish species in southern China. During intensive aquaculture, hybrid snakeheads are often infected by Nocardia seriolae. In this study, hybrid snakehead infected suspiciously by N. seriolae in an artificial breeding pond were examined. Diseased hybrid snakeheads swam slowly without food intake, and the clinical symptoms included skin wound, anal swelling and ascites, and white granulomatous in liver, spleen, and kidney of fish. Through bacterial isolation, 16S rDNA sequencing, fluorescence in situ hybridization (FISH) and artificial infection experiment, the pathogen was identified as N. seriolae. Furthermore, the spleen samples from diseased and healthy male hybrid snakeheads in the same pond were used for RNA-Seq analysis. A total of 3,512 unique transcripts (unigenes) were identified as differentially expressed genes (DEGs), and 1,886 of them were up-regulated in diseased fish. The expression patterns of 20 DEGs were verified by quantitative polymerase chain reaction (qPCR). Several immune-related pathways and many immune-related genes were identified. qPCR results showed that the expression patterns of immune-related genes in the liver and kidney of diseased fish were comparable to that in the spleen. This study provides deep-sequencing data of hybrid snakehead spleen and will help understand the immune response of hybrid snakehead to N. seriolae. It is also helpful for the biomarker screening of fish-borne Nocardia spp. and the breeding of nocardiosis-resistant fish species.

An explainable integrated optimization methodology for source apportionment of ambient particulate matter components.

Source apportionment of fine particulate matter (PM2.5) components is crucial for air pollution control. Prediction accuracies by the chemical transport model (CTM) significantly affect source apportionment results. Many efforts have been made to improve source apportionment results based on the CTM using mathematical algorithms, but the reasons for uncertainties in source apportionment results are less concerned. Here, an integrated optimization methodology is developed to quantify deviations from emission inventory and chemical mechanism in the model for improving prediction and source apportionment accuracies. Emission deviations of primary aerosols and gaseous pollutants are firstly calculated by an optimization algorithm with observation and receptor model constraints. Emission inventory is then adjusted for a new CTM simulation. Deviations from chemical mechanism for secondary conversions are evaluated by biases between observations and new predictions. Source apportionment results are adjusted according to both emission and chemical mechanism deviations. A winter month in 2016 at the Qingpu supersite in eastern China is selected as a case study. Results show that our integrated optimization methodology can successfully adjust emissions to pull original predictions towards observations. Total deviations of emissions for elemental carbon, organic carbon, primary sulfate, primary nitrate, primary ammonium, sulfur dioxide (SO2), nitrogen oxides (NOx) and ammonia (NH3) are estimated +59.6%, +95.9%, +72.9%, +82.2%, +75.9%, -6.4%, +67.6% and -17.6%, respectively. Also, major directions of deviations from chemical mechanisms can be captured. Deviations from SO2 to secondary sulfate, nitrogen dioxide (NO2) to secondary nitrate and NH3 to secondary ammonium conversions are estimated -77.3%, +27.1% and -38.8%, respectively. Consequently, source apportionment results are significantly improved. This developed methodology provides an efficient way to quantify deviations from emissions and chemical mechanisms to improve source apportionment for air pollution management.

Contamination characteristics, source analysis and health risk assessment of heavy metals in the soil in Shi River Basin in China based on high density sampling.

To explore the contamination of heavy metals in the Shi River Basin soil in China, a high density sampling of surface soil was conducted. In this study, an absolute principal component scores multiple linear regression model (APCS-MLR) was used to identify the sources of heavy metals in the soil and quantify their amounts. The methods to assess the heavy metals included a fuzzy synthetic evaluation, index and health risk assessment. The results show that heavy metals are relatively rich southwest of the study area. Their levels may be affected by natural sources, such as parent materials. The pollution caused by human factors cannot be ignored, and it is primarily influenced by traffic emissions and processing sources, which contribute 62.6%, followed by agricultural sources, such as pesticides and fertilizers, that contribute 21.1%. The risk assessment indicated that the study area was slightly to moderately polluted. All heavy metals pose higher carcinogenic and other health risks to children than adults, and ingestion is the main way that these pollutants enter the body. The carcinogenic risk of children owing to Cr from natural sources merits further study, while the carcinogenic risk to adults and the non-carcinogenic risk to both adults and children are at acceptable levels. Transportation and industrial processing sources are the main cause of the non-carcinogenic risk. The results could provide reference for reducing heavy metal pollution in the soil.

Geochemical Characteristics and Ecological Risk Assessment of Heavy Metals in Surface Soil of Gaomi City.

Gaomi City, the hinterland of Jiaolai Plain in Shandong Peninsula, was selected as the research object. A total of 8197 surface soil samples were collected to determine the contents of eight soil heavy metals (HMs)including Copper (Cu), Lead (Pb), Zinc (Zn), Nickel (Ni), Chromium (Cr), Cadmium (Cd), Arsenic (As), and Mercury (Hg). Statistical methods were used to find out the geochemical background (GCB) in the area, systematic clustering and factor analysis were used to study the homology between HMs, and single-factor evaluation method was used to evaluate the ecological risks in the study area. The results of the study show that the ecological risk of the surface soil in the study area is relatively low, dominated by a planar distribution, with only a few high-risk points. The uneven distribution of Hg in the surface soil is affected by human activities to a certain extent. The ratio of the GCB of the geological unit area to the GCB of the whole area shows that the Hg content of the Qingshan Group and Dasheng Group geological units is higher, and the Pb content in the subvolcanic rock area is slightly higher. The ecological pollution risk in the study area is generally low, and only exists individual high-risk areas, distributed radially in densely populated areas.

Source and Health Risk Assessment of Heavy Metals in Soil-Ginger System in the Jing River Basin of Shandong Province, North China.

This study investigated the characteristics and sources of heavy metals in a soil-ginger system and assessed their health risks. To this end, 321 topsoil samples and eight soil samples from a soil profile, and 18 ginger samples with root-soil were collected from a ginger-planting area in the Jing River Basin. The average concentration of heavy metals in the topsoil followed the order: Cr > Zn > Pb > Ni > Cu > As > Cd > Hg. In the soil profile, at depths greater than 80 cm, the contents of Cr, Ni, and Zn tended to increase with depth, which may be related to the parent materials, whereas As and Cu contents showed little change. In contrast, Pb content decreased sharply from top to bottom, which may be attributable to external environmental and anthropogenic factors. Multivariate statistical analysis showed that Cr, Ni, Cu, Zn, and Cd contents in soil are affected by natural sources, Pb and As contents are significantly affected by human activities, and Hg content is affected by farmland irrigation. Combined results of the single pollution index (Pi), geo-accumulation index (Igeo), and potential ecological risk assessment (Ei and RI) suggest that soil in the study area is generally not polluted by heavy metals. In ginger, Zn content was the highest (2.36 mg/kg) and Hg content was the lowest (0.0015 mg/kg). Based on the bioconcentration factor, Cd and Zn have high potential for enrichment in ginger. With reference to the limit of heavy metals in tubers, Cr content in ginger exceeds the standard in the study area. Although Cr does not accumulate in ginger, Cr enrichment in soil significantly increases the risk of excessive Cr content in ginger.

Development of PEGylated chitosan/CRISPR-Cas9 dry powders for pulmonary delivery via thin-film freeze-drying.

Gene therapy and more recently, gene editing is attractive via pulmonary delivery for enhanced regional targeting. However, processing of sensitive therapeutics into dry powders for inhalation can be problematic due to relatively stressful spraying or milling steps. Thin-film freeze-drying (TFFD) has attracted attention with its promising application in the production of DPI formulations possessing respirable particle size range (1-5 µm) particularly for thermally or shear sensitive therapeutics. In this study, gene editing dry powder formulations containing PEGylated chitosan/CRISPR-Cas9 nanocomplexes were prepared by TFFD. To evaluate stability during processing, nanocomplex size, zeta potential and transfection efficiency of reconstituted formulations were evaluated, and six potential DPI formulations were identified and characterized in terms of geometric particle size, powder surface morphology, and crystallinity. It was found that two formulations containing 3% mannitol with or without leucine were identified as suitable for inhalation with a desired aerodynamic performance. The flow rate dependency and inhaler dependency of these two formulations were also evaluated at different flow rates (60 L/min and 45 L/min) and different inhaler devices (RS01 DPI and HandiHaler) using NGI testing. This study demonstrated that TFFD processing of CRISPR-Cas9 polymer nanocomplexes resulted in a suitable dry powder for inhalation.

Prevalence and risk factors for repeat induced abortion among Chinese women: a systematic review and meta-analysis.

OBJECTIVES: Repeat induced abortion is a significant public health problem in China. International knowledge about repeat induced abortion and its associated risk factors in Chinese women is scarce, and existing studies are hard to access for international scholars because most are published in Chinese. A systematic review was conducted to analyse the prevalence of repeat induced abortion among Chinese women and determine correlated risk factors. METHODS: Seven electronic databases were systematically searched. Data on the prevalence of repeat induced abortion and related factors were extracted and pooled using a meta-analysis and narrative approach. RESULTS: Of 2458 articles retrieved from seven databases, 21 were included in the study. The overall pooled prevalence of repeat induced abortion was 43.1% (95% confidence interval 36.7%, 49.5%). Of 25 exposures extracted, 15 factors were significantly correlated with repeat induced abortion, comprising seven individual demographic factors (i.e., age, education, employment, migrant status, parity, unhealthy lifestyle habits and region of residence), four reproductive health- and contraception-related factors (i.e., age at sexual debut, history of sexual activity, contraceptive knowledge and having a regular sexual life) and four sexual partner-related factors (i.e., multiple sexual partners, age of sexual partner, educational level of sexual partner and cohabitation with sexual partner). CONCLUSION: The study findings highlight the problem of repeat induced abortion in China and suggest the need for government and civil society to increase efforts to reduce the alarming risks of repeat induced abortion in Chinese women and make them and their sexual partners more aware and protective of their sexual and reproductive health.

Aerosolizable Lipid Nanoparticles for Pulmonary Delivery of mRNA through Design of Experiments.

Messenger RNA is a class of promising nucleic acid therapeutics to treat a variety of diseases, including genetic diseases. The development of a stable and efficacious mRNA pulmonary delivery system would enable high therapeutic concentrations locally in the lungs to improve efficacy and limit potential toxicities. In this study, we employed a Design of Experiments (DOE) strategy to screen a library of lipid nanoparticle compositions to identify formulations possessing high potency both before and after aerosolization. Lipid nanoparticles (LNPs) showed stable physicochemical properties for at least 14 days of storage at 4 °C, and most formulations exhibited high encapsulation efficiencies greater than 80%. Generally, upon nebulization, LNP formulations showed increased particle size and decreased encapsulation efficiencies. An increasing molar ratio of poly-(ethylene) glycol (PEG)-lipid significantly decreased size but also intracellular protein expression of mRNA. We identified four formulations possessing higher intracellular protein expression ability in vitro even after aerosolization which were then assessed in in vivo studies. It was found that luciferase protein was predominately expressed in the mouse lung for the four lead formulations before and after nebulization. This study demonstrated that LNPs hold promise to be applied for aerosolization-mediated pulmonary mRNA delivery.

Just how prevalent are peptide therapeutic products? A critical review.

How prevalent are peptide therapeutic products? How innovative are the formulations used to deliver peptides? This review provides a critical analysis of therapeutic peptide products and the formulations approved by the United States Food and Drug administration (FDA), the European Medicines Agency (EMA), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). This review also provides an in-depth analysis of dosage forms and administration routes for delivering peptide therapeutics, including injectables, oral dosage forms, and other routes of administration. We discuss the function of excipients in parenteral formulations in detail, since most peptide therapeutics are parenterally administered. We provide case studies of alternate delivery routes and dosage forms. Based on our analysis, therapeutic peptides administered as injectables remain the most commonly used dosage forms, particularly in the form of subcutaneous, intravenous, or intramuscular injections. In addition, therapeutic peptides are formulated to achieve prolonged release, often through the use of polymer carriers. The limited number of oral therapeutic peptide products and their poor absorption and subsequent low bioavailability indicate a need for new technologies to broaden the formulation design space. Therapeutic peptide products may also be delivered through other administration routes, including intranasal, implant, and sublingual routes. Therefore, an in-depth understanding of how therapeutic peptides are now formulated and administered is essential to improve peptide delivery, improve patient compliance, and reduce the healthcare burden for these crucial therapeutic agents.

The Stabilizing Excipients in Dry State Therapeutic Phage Formulations.

Phage therapy has gained prominence due to the increasing pathogenicity of "super bugs" and the rise of their multidrug resistance to conventional antibiotics. Dry state formulation of therapeutic phage is attractive to improve their "druggability" by increasing their shelf life, improving their ease of handling, and ultimately retaining their long-term potency. The use and selection of excipients are critical to stabilize phage in solid formulations and protect their viability from stresses encountered during the solidification process and long-term storage prior to use. Here, this review focuses on the current classes of excipients used to manufacture dry state phage formulations and their ability to stabilize and protect phage throughout the process, as discussed in the literature. We provide perspective of outstanding challenges involved in the formulation of dry state phage. We suggest strategies to improve excipient identification and selection, optimize the potential excipient combinations to improve phage viability during formulation, and evaluate new methodologies that can provide greater insight into phage-excipient interactions to improve design criteria to improve formulation of dry state phage therapeutics. Addressing these challenges opens up new opportunities to re-design and re-imagine phage formulations for improved efficacy as a pharmaceutical product.