Study of vascular sclerosing agent based on the dual mechanism of vascular endothelial cell damage-plasmin system inhibition.

Venous malformations are a vascular disorder. Currently, the use of chemical sclerosing agents is a common clinical approach for the treatment of venous malformations. However, the effectiveness of existing sclerosing agents is unsatisfactory and often accompanied by severe side effects. In this study, we have developed a novel cationic surfactant-based sclerosing agent (POL-TA) by conjugating the plasmin inhibitor tranexamic acid (TA) with a nonionic surfactant polidocanol (POL) through an ester bond. POL-TA induces endothelial cell damage, triggering the coagulation cascade and thrombus formation. Moreover, it releases TA in vivo, which inhibits plasmin activity and the activation of matrix metalloproteinase (MMPs), thereby stabilizing the fibrin network of the thrombus and promoting vascular fibrosis. We have established a cell model using venous malformation endothelial cells and assessed the cellular damage and underlying mechanisms of POL-TA. The inhibitory effects of POL-TA on the plasmin-MMPs system were evaluated using MMP-9 activity assay kit. Additionally, the mice tail vein model was employed to investigate the vascular sclerosing effects and mechanisms of POL-TA.

Erythrocyte Membrane-Coated Invisible Acoustic-Sensitive Nanoparticle for Inducing Tumor Thrombotic Infarction by Precisely Damaging Tumor Vascular Endothelium.

Selective induction of tumor thrombus infarction is a promising antitumor strategy. Non-persistent embolism due to non-compacted thrombus and activated fibrinolytic system within the tumor large blood vessels and tumor margin recurrence are the main therapeutic bottlenecks. Herein, an erythrocyte membrane-coated invisible acoustic-sensitive nanoparticle (TXA+DOX/PFH/RBCM@cRGD) is described, which can induce tumor thrombus infarction by precisely damaging tumor vascular endothelium. It is revealed that TXA+DOX/PFH/RBCM@cRGD can effectively accumulate on the endothelial surface of tumor vessels with the help of the red blood cell membrane (RBCM) stealth coating and RGD cyclic peptide (cRGD), which can be delivered in a targeted manner as nanoparticle missiles. As a kind of phase-change material, perfluorohexane (PFH) nanodroplets possess excellent acoustic responsiveness. Acoustic-sensitive missiles can undergo an acoustic phase transition and intense cavitation with response to low-intensity focused ultrasound (LIFU), damaging the tumor vascular endothelium, rapidly initiating the coagulation cascade, and forming thromboembolism in the tumor vessels. The drugs loaded in the inner water phase are released explosively. Tranexamic acid (TXA) inhibits the fibrinolytic system, and doxorubicin (DOX) eliminates the margin survival. In summary, a stealthy and acoustically responsive multifunctional nanoparticle delivery platform is successfully developed for inducing thrombus infarction by precisely damaging tumor vascular endothelium.

Nuclear localization signal peptide enhances transfection efficiency and decreases cytotoxicity of poly(agmatine/N,N'-cystamine-bis-acrylamide)/pDNA complexes.

At present, nonviral gene vectors develop rapidly, especially cationic polymers. A series of bioreducible poly(amide amine) (PAA) polymers containing guanidino groups have been synthesized by our research team. These novel polymer vectors demonstrated significantly higher transfection efficiency and lower cytotoxicity than polyethylenimine (PEI)-25kDa. However, compared with viral gene vectors, relatively low transfection efficiency, and high cytotoxicity are still critical problems confronting these polymers. In this study, poly(agmatine/N,N'-cystamine-bis-acrylamide) p(AGM-CBA) was selected as a model polymer, nuclear localization signal (NLS) peptide PV7 (PKKKRKV) with good biocompatibility and nuclear localization effect was introduced to investigate its impact on transfection efficiency and cytotoxicity. NLS peptide-mediated in vitro transfection was performed in NIH 3T3 cells by directly incorporating NLS peptide with the complexes of p(AGM-CBA)/pDNA. Meanwhile, the transfection efficiency and cytotoxicity of these complexes were evaluated. The results showed that the transfection efficiency could be increased by 5.7 times under the appropriate proportion, and the cytotoxicity brought by the polymer vector could be significantly reduced.

Nuclear delivery of plasmid DNA determines the efficiency of gene expression.

As a cationic non-viral gene delivery vector, poly(agmatine/ N, N'-cystamine-bis-acrylamide) (AGM-CBA) showed significantly higher plasmid DNA (pDNA) transfection ability than polyethylenimine (PEI) in NIH/3T3 cells. The transfection expression of AGM-CBA/pDNA polyplexes was found to have a non-linear relationship with AGM-CBA/pDNA weight ratios. To further investigate the mechanism involved in the transfection process of poly(AGM-CBA), we used pGL3-control luciferase reporter gene (pLUC) as a reporter pDNA in this study. The distribution of pLUC in NIH/3T3 cells and nuclei after AGM-CBA/pLUC and PEI/pLUC transfection were determined by quantitative polymerase chain reaction (qPCR) analysis. The intracellular trafficking of the polyplexes was evaluated by cellular uptake and nuclei delivery of pLUC, and the intracellular availability was evaluated by the ratio of transfection expression to the numbers of pLUC delivered in nuclei. It was found that pLUC intracellular trafficking did not have any correlation with the transfection expression, while an excellent correlation was found between the nuclei pLUC availability and transfection expression. These results suggested that the intracellular availability of pLUC in nuclei was the rate-limiting step for pLUC transfection expression. Further optimization of the non-viral gene delivery system can be focused on the improvement of gene intracellular availability.

Disulfide-bond-containing agamatine-cystaminebisacrylamide polymer demonstrates better transfection efficiency and lower cytotoxicity than polyethylenimine in NIH/3T3 cells.

Previously, we synthesized a non-viral vector containing disulfide bond by polymerization of agamatine (AGM) and N,N'-cystaminebisacrylamide (CBA). In this study, we investigated the transfection efficiency of disulfide bond (SS) containing AGM-CBA polymer in gene delivery into NIH/3T3 cells, and examined the factors affecting its transfection efficiency by comparing with polyethylenimine (PEI). In addition, experiments were carried out to determine the mechanisms of cell entry pathways and intracellular behavior of AGM-CBA/pDNA polyplexes. The transfection efficiency of AGM-CBA/pDNA with different weight ratios and different amounts of pDNA was measured and the pathways mediated transfection processes were studied by using various endocytosis inhibitors. To determine the intracellular behavior of AGM-CBA/pDNA polyplexes, the transfection efficiencies of AGM-CBA/pDNA and PEI/pDNA polyplexes with different combination structures were determined by using reporter gene and fake plasmid DNA. The transfection efficiency of AGM-CBA/pDNA polyplexes was correlated with its weight ratio of AGM-CBA and pDNA, and the amount of pDNA. Both AGM-CBA/pDNA and PEI/pDNA polyplexes enter into cell by clathrin- and caveolae-mediated endocytic pathways. However, AGM-CBA/pDNA showed different intracellular behavior in NIH/3T3 cells compared to PEI/pDNA polyplexes. It was hypothesized that disulfide bond in AGM-CBA could be an important factor contributing to its intracellular behavior and better transfection efficiency. Overall, AGM-CBA demonstrated better transfection efficiency and lower cytotoxicity than PEI in NIH/3T3 cells as a gene delivery vector.

Transdermal Cubic Phases of Metformin Hydrochloride: In Silico and in Vitro Studies of Delivery Mechanisms.

Transdermal delivery is one of important controlled drug release strategies for drug development. Cubic phases are the assemblies of amphiphilic molecules in water with the hydrophilic-hydrophobic interpenetrating network for transdermal delivery of both hydrophilic and hydrophobic drugs. However, many details about the transdermal delivery of drugs from cubic phases remain unclear. Here, metformin hydrochloride (Met) cubic phases were prepared with glyceryl monooleate (GMO), ethanol, and water. The cubic structure was identified with the polarizing light microscopy and small-angle X-ray scattering method. Dissipative particle dynamics (DPD) was used for building the microstructures of the cubic phases to explore the mechanism of drug release that mainly depended on drug diffusion from the water channels of cubic phases in accordance with the Higuchi equation of in vitro release experiments. The coarse-grained model and molecular docking method showed that GMO could enhance drug permeation through the skin by disturbing the interaction between Met and the skin proteins, and increasing the fluidity of skin lipids, which was confirmed with the Fourier transform infrared spectroscopy, Langmuir monolayer, and immunohistochemistry. Furthermore, in vitro permeation experiments showed the high Met transdermal improvement of cubic phases. Cubic phases are an ideal transdermal delivery system of Met. In silico methods are very useful for analyzing the molecular mechanisms of transdermal formulations.

Uptake Pathways of Guandinylated Disulfide Containing Polymers as Nonviral Gene Carrier Delivering DNA to Cells.

Polymers of guanidinylated disulfide containing poly(amido amine)s (Gua-SS-PAAs), have shown high transfection efficiency and low cytotoxicity. Previously, we synthesized two Gua-SS-PAA polymers, using guanidino containing monomers (i.e., arginine and agmatine, denoted as ARG and AGM, respectively) and N,N'-cystaminebisacrylamide (CBA). In this study, these two polymers, AGM-CBA and ARG-CBA were complexed with plasmid DNA, and their uptake pathway was investigated. Complexes distribution in MCF-7 cells, and changes on cell endosomes/lysosomes and membrane after the cells were exposed to complexes were tested. In addition, how the transfection efficiency changed with the cell cycle status as well as endocytosis inhibitors were studied. The polymers of AGM-CBA and ARG-CBA can avoid endosomal/lysosomal trap, therefore, greatly delivering plasmid DNA (pDNA) to the cell nucleoli. It is the guanidine groups in the polymers that enhanced complexes' permeation through cell membrane with slight membrane damage, and targeting to the nucleoli. J. Cell. Biochem. 118: 903-913, 2017. © 2016 Wiley Periodicals, Inc.

Dissolution enhancement of tadalafil by liquisolid technique.

This study aimed to enhance the dissolution of tadalafil, a poorly water-soluble drug by applying liquisolid technique. The effects of two critical formulation variables, namely drug concentration (17.5% and 35%, w/w) and excipients ratio (10, 15 and 20) on dissolution rates were investigated. Pre-compression tests, including particle size distribution, flowability determination, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM), were carried out to investigate the mechanism of dissolution enhancement. Tadalafil liquisolid tablets were prepared and their quality control tests, dissolution study, contact angle measurement, Raman mapping, and storage stability test were performed. The results suggested that all the liquisolid tablets exhibited significantly higher dissolution rates than the conventional tablets and pure tadalafil. FT-IR spectrum reflected no drug-excipient interactions. DSC and XRD studies indicated reduction in crystallinity of tadalafil, which was further confirmed by SEM and Raman mapping outcomes. The contact angle measurement demonstrated obvious increase in wetting property. Taken together, the reduction of particle size and crystallinity, and the improvement of wettability were the main mechanisms for the enhanced dissolution rate. No significant changes were observed in drug crystallinity and dissolution behavior after storage based on XRD, SEM and dissolution results.

A method for the preparation of sustained release-coated Metoprolol Succinate pellet-containing tablets.

The purpose of this study was to develop a method to prepare Metoprolol Succinate (MS) sustained release pellets and compress them into pellet-containing tablets without losing sustained release property. The drug layered pellets were coated with Eudragit NE 30D to obtain a sustained release (SR) property. The mechanical properties and permeability of the coating film were tailored by adjusting the proportion of talc in the coating dispersion and the weight gain of the coating film. Pellets with different MS release rates were tested and then mixed together by different ratios to optimize drug release rate. The mixed pellets were compressed into tablets with cushioning excipients. The results showed that when the ratio of talc and coating material was 1:4, the coating operation could be conducted successfully without pellet conglutination and the mechanical property of the coating film was enhanced to withstand the compress force during tableting. Blending SR-coated pellets of 20% weight gain with SR-coated pellets of 40% weight gain at the ratio of 1:5 could produce a constant and desired drug release rate. The formulation and the procedure developed in the study were suitable to prepare MS pellet-containing tablets with selected SR properties.

Microdialysis as a tool to determine the skin concentration of mometason furoate in rats.

The objective of this study was to investigate the feasibility of microdialysis as a tool to determine the skin concentration of mometason furoate (MF), a lipophilic and highly protein-bound compound. The relative recovery (RR) of mometasone furoate was determined by an in vitro no-net-flux method using three different perfusates (40% PEG400, 5% fat emulsion, and 20% fat emulsion) and four flow rates (0.5, 1, 2, and 4 µL x min(-1)). With the increasing of flow rate, the relative recovery was decreased from 48.8% to 3.1%. The in vitro recovery was increased to 23.71%, 42.76% and 56.21% when 40% PEG400, 5% fat emulsion or 20% fat emulsion was used as microdialysis perfusates, respectively. Fat emulsion (5%) was chosen as the perfusate to evaluate the in vivo recovery by a retrodialysis method, in which mometasone furoate concentration in different tissues was determined. The result showed that concentrations of mometasone furoate in the dermis was greater than that in the subcutaneous or muscle tissue. It was concluded that a recovery enhancer could be used in microdialysis technique, especially for determining skin concentrations of lipophilic and high protein-bounds.

RETRACTED: Chen et al. A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy. Pharmaceutics 2022, 14, 343.

The Pharmaceutics Editorial Office retracts the article, "A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy" [...].

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy.

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvß3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Predatory bacterial hydrogels for topical treatment of infected wounds.

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 µm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

Fabrication of human serum albumin-imprinted photothermal nanoparticles for enhanced immunotherapy.

Photothermal nanoparticles have been confirmed to induce an antitumor immune response and turn "cold tumor" into "hot tumor". However, their delivery efficacy to tumors is limited by the elimination from the reticalendothel system. Herein, human serum albumin (HSA)-imprinted polymer coated Fe3O4 nanoparticles (Fe3O4@MIPs) are fabricated by oxidative polymerization of dopamine in the presence of HSA on the polydopamine pre-modified Fe3O4 nanoparticle surface, followed by the removal of HSA. The Fe3O4@MIPs exhibit rapid and specific reabsorption toward HSA. The molecularly imprinted sites on the Fe3O4@MIPs endow it with an albumin-rich protein corona in the blood and result in less elimination from the reticalendothel system than non-albumin-imprinted particles (Fe3O4@NIPs). Moreover, the molecularly imprinted polymer, which consists of polydopamine, also improves the photothermal effect of Fe3O4 nanoparticles. In vivo, the albumin camouflage in Fe3O4@MIPs produces a 2.6-fold improvement in tumor accumulation in comparison to Fe3O4@NIPs, and more heat is produced upon 808 nm laser irradiation, which further triggers an efficient immunogenic cell death (ICD) progress. Thus, the combination of Fe3O4@MIPs and PD-L1 antibody can not only inhibit the growth of primary tumors but also eliminates lung metastasis by eliciting immunological effect.

A Novel Drug Self-Delivery System from Fatty Alcohol Esters of Tranexamic Acid for Venous Malformation Sclerotherapy.

Venous malformation (VM), which causes severe damage to patients' appearance and organ function, is one of the most common vascular malformations. At present, many drugs in clinical treatment cause various adverse reactions. Herein, we synthesized cationic amphiphilic gelators (TA6, TA8, and TA9) by introducing saturated carbon chains of different lengths to tranexamic acid (TA), which could self-assemble into low-molecular-weight gels (LMWGs) as drug delivery carriers by hydrogen bonds, van der Waals forces, and hydrophobic interactions. The rheological properties, gelation driving force and drug release profiles of TA6, TA8, and TA9 hydrogels were characterized, and the results indicated that the hydrogels prepared in this study possessed the typical characteristics of a gel and could release drugs slowly. More importantly, the TA9 gelator showed significant pharmacological activity, in that it served as both an active drug compound and a drug carrier. The in vitro experiments demonstrated that TA9 induced HUVECs death and hemolysis by destroying cell membranes in a dose-dependent manner, and caused cell death and hemolysis at a concentration of 0.09 µM/mL. Meanwhile, we found TA9 could interact not only with fibrinogen, but also with other endogenous molecules in the blood. After the administration of TA9 hydrogel for 15 days, macroscopic imaging and histological evaluation in mice and rabbits displayed obvious thrombi, inflammatory reactions, and venous embolization, indicating that the mechanism of the TA9 hydrogel in treating VM was involved in two processes. Firstly, the TA9 hydrogel relied on its mechanical strength to physically block veins and continuously release TA9, in situ, for targeted therapy. Then, TA9 destroyed endothelial cells and damaged venous walls critically, causing thrombi. Most excitingly, TA9 was hydrolyzed to TA by enzymes that inhibited the degradation of thrombi by plasmin to prolong the embolization time and to promote venous fibrosis. Compared with other clinically available sclerosants, the degradation of TA9 also empowered a better biocompatibility and biodegradability for the TA9 hydrogel. In conclusion, we synthesized a potentially safe and effective derivative of TA and developed a low-molecular-weight gel as a self-delivery system for TA in treating VM.

Glycyrrhetinic acid modified chlorambucil prodrug for hepatocellular carcinoma treatment based on DNA replication and tumor microenvironment.

Chlorambucil (CLB) is widely used in the treatment of solid tumors. However, CLB has poor water solubility, short half-life and side effects such as leucopenia and thrombocytopenia, in addition to the inhibition of tumor immune microenvironment. In our study, chlorambucil-chitosan (CLB-CS) prodrug micelles were successfully prepared, and glycyrrhetinic acid (GA) was selected, which could improve the immunosuppressive microenvironment and actively targeted liver cancer cells. At the tumor site, CLB blocked the cell cycle and promoted apoptosis. In addition, GA improved the tumor microenvironment by increasing the proportion of CD4+T and CD8+T cells at the tumor site, and promoting the differentiation of CD4+T cells into Th1 cells, thereby reducing the proportion of Treg and Th2 cell subsets, so as to offset the adverse factors of CLB against tumor immunity. By interfering with DNA replication and modulating the tumor microenvironment, GA/CLB-CS micelles enabled the effective treatment of liver cancer.

"PFH/AGM-CBA/HSV-TK/LIPOSOME-Affibody": Novel Targeted Nano Ultrasound Contrast Agents for Ultrasound Imaging and Inhibited the Growth of ErbB2-Overexpressing Gastric Cancer Cells.

Objective: Gastric cancer is one of the most lethal malignancies in the world. However, the current research on the diagnosis and treatment of nano-ultrasound contrast agents in the field of tumor is mostly focused on breast cancer, ovarian cancer, prostate cancer, liver cancer, etc. Due to the interference of gas in the stomach, there is no report on the treatment of gastric cancer. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) therapy system is the most mature tumor suicide gene in cancer treatment. At the same time, in order to improve its safety and efficiency, we designed a gastric tumor targeted ultrasound-triggered phase-transition nano ultrasound contrast agent PFH/AGM-CBA/HSV-TK/Liposome (PAHL)-Affibody complex. Methods: In our study, guanidinylated SS-PAAs polymer poly(agmatine/N, N'-cystamine-bis-acrylamide) (AGM-CBA) was used as a nuclear localization vector of suicide gene to form a polyplex, perfluorohexane (PFH) was used as ultrasound contrast agent, liposomes were used to encapsulate perfluorohexane droplets and the polyplexes of AGM-CBA/HSV-TK, and affibody molecules were conjugated to the prepared PAHL in order to obtain a specific targeting affinity to human epidermal growth factor receptor type 2 (ErbB2) at gastric cancer cells. With the aid of ultrasound targeted microbubble destruction technology and the nuclear localization effect of AGM-CBA vector, the transfection efficiency of the suicide gene in gastric cancer cells was significantly increased, leading to significant apoptosis of gastric cancer cells. Results: It was shown that PAHL-Affibody complex was nearly spherical with an average diameter of 560 ± 28.9 nm, having higher and specific affinity to ErbB2 (+) gastric cells. In vitro experiments further confirmed that PAHL could target gastric cancer cells expressing ErbB2. In a contrast-enhanced ultrasound scanning study, the prepared ultrasound-triggered phase-change nano-ultrasound contrast agent, PAHL, showed improved ultrasound enhancement effects. With the application of the low-frequency ultrasound, the gene transfection efficiency of PAHL was significantly improved,  thereby inducing significant apoptosis in gastric cancer cells. Conclusion: This study constructs PFH/AGM-CBA/HSV-TK/Liposome-Affibody nano ultrasound contrast agent, which provides new ideas for the treatment strategy of ErbB2-positive gastric cancer and provides some preliminary experimental basis for its inhibitory effect.

A wearable gamma radiation-responsive granulocyte colony-stimulating factor microneedle system protecting against ionizing radiation-induced injury.

Exposure to a nuclear accident or a radiological attack may cause serious death events due to ionizing radiation-induced injury and acute radiation syndrome (ARS). Recombinant human granulocyte colony-stimulating factor (G-CSF) is now used for the treatment of ARS. However, the current injection formulation might not ensure treatment as early as possible after a nuclear accident, resulting in a decrease in therapeutic efficiency. In the present study, we have developed a G-CSF wearable system (GWS) consisting of a commercial microchip, a temperature sensor, a gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle (GTSMN) patch. G-CSF-containing hyaluronic acid solutions were cast into the mold to obtain G-CSF microneedles (GMNs), which were coated with a temperature-sensitive layer of dodecanoic acid-cetylamine salt to obtain GTSMNs. The flexible heater was prepared by jet printing Ag nanoparticle inks. The GWS and its components are explored and optimized in the aspects of electronics, mechanics, heat transfer and drug diffusion. The γ radiation signal is sensitively monitored by the GWS. The wearable G-CSF system immediately releases G-CSF into the body in response to signal feedback and provides maximal protection against ionizing radiation-induced injury. Therefore, the GWS is a promising wearable system against emergent ionizing radiation injury. STATEMENT OF SIGNIFICANCE: Ionizing radiation-induced injury is always the very important public health problem all the global people care. Some medicines have been applied to protect the body from the injury. Unfortunately, sometimes the injuries accidently happen and the medicines cannot be administered in time, leading to serious acute radiation syndrome. Here, we design a wearable system loading G-CSF that has been approved by FDA to protect the body from ionizing radiation-induced injury. This system consists of a commercial microchip, a temperature sensor, a Gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle patch. It can monitor γ radiation and immediately release G-CSF into the body to protect the body to the maximal extent. Therefore, the system is a promising wearable medical device against emergent ionizing radiation injury.

Cell-free protein synthesis of influenza virus hemagglutinin HA2-integrated virosomes for siRNA delivery.

It is well known that the difficulty of siRNA therapeutic application is the lack of safe and effective delivery vector. Virosome is a nano vesicle composed of lipid membrane and membrane protein. It retains fusion protein without virus genetic material, and therefore has the reduced immunogenicity compared with viral vector. Virosomes have the potential to deliver protein and nucleic acid drugs, but the traditional preparation method of virosomes is quite limited. In this study, we firstly proposed to synthesize influenza virus hemagglutinin HA2 virosomes by cell-free protein synthesis. In this study, liposomes provided the hydrophobic lipid bilayer environment for the formation of HA2 protein multimer, which inhibited the aggregation of hydrophobic HA2 and improved HA2 protein expression. Chitosan as a rigid core adsorbed siRNA and improved the encapsulation efficiency of siRNA. In conclusion, the cell-free protein synthesis was used to prepare HA2 virosomes, which paves the way for constructing a novel nano vector with high delivery efficiency and biosafety for the delivery of siRNA.

Opportunities and challenges of three-dimensional printing technology in pharmaceutical formulation development.

Three-dimensional printing is a technology that prints the products layer-by-layer, in which materials are deposited according to the digital model designed by computer aided design (CAD) software. This technology has competitive advantages regarding product design complexity, product personalization, and on-demand manufacturing. The emergence of 3D technology provides innovative strategies and new ways to develop novel drug delivery systems. This review summarizes the application of 3D printing technologies in the pharmaceutical field, with an emphasis on the advantages of 3D printing technologies for achieving rapid drug delivery, personalized drug delivery, compound drug delivery and customized drug delivery. In addition, this article illustrates the limitations and challenges of 3D printing technologies in the field of pharmaceutical formulation development.