Choline and geranate ionic liquid for subgingival biofilm control.

Periodontitis is a chronic inflammatory disease that causes destruction of the periodontium and eventual tooth loss. The priority in the periodontal treatment is to remove the subgingival biofilm. Chemical removal of biofilms using antimicrobial agents has been applied in clinical practice.

Total Synthesis of Bipenicilisorin and Assignment of the Absolute Configuration.

The first total synthesis of bipenicilisorin () isolated from SCSIO 41001 via its monomer natural product, penicilisorin (), was achieved. Penicilisorin was synthesized in four steps from a -bromobenzaldehyde derivative via the Pd-catalyzed one-pot fluorocarbonylation/lactonization/β-elimination cascade reaction. Iodination of penicilisorin gave 7-iodopenicilisorin which was dimerized by Pd-catalyzed homodimerization to provide (±)-bipenicilisorin.

Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy.

Tumour-associated neutrophils can exert antitumour effects but can also assume a pro-tumoural phenotype in the immunosuppressive tumour microenvironment. Here we show that neutrophils can be polarized towards the antitumour phenotype by discoidal polymer micrometric 'patches' that adhere to the neutrophils' surfaces without being internalized. Intravenously administered micropatch-loaded neutrophils accumulated in the spleen and in tumour-draining lymph nodes, and activated splenic natural killer cells and T cells, increasing the accumulation of dendritic cells and natural killer cells.

Acute Kidney Injury Caused by Rhabdomyolysis Is Ameliorated by Serum Albumin-Based Supersulfide Donors through Antioxidative Pathways.

Oxidative stress is responsible for the onset and progression of various kinds of diseases including rhabdomyolysis-induced acute kidney injury (AKI). Antioxidants are, therefore, thought to aid in the recovery of illnesses linked to oxidative stress. Supersulfide species have been shown to have substantial antioxidative activity; however, due to their limited bioavailability, few supersulfide donors have had their actions evaluated in vivo.

[Characterization of Supersulfide in Serum Albumin and Its Therapeutic Application].

Recent studies have shown that proteins already possess supersulfides during the translation. However, the distribution and the role of supersulfides are not fully understood. In this review, we focus on supersulfides in biological fluids, especially in serum.

Design of an Anti-HMGB1 Synthetic Antibody for Ischemic/Reperfusion Injury Therapy.

High-mobility group box 1 (HMGB1) is a multifunctional protein. Upon injury or infection, HMGB1 is passively released from necrotic and activated dendritic cells and macrophages, where it functions as a cytokine, acting as a ligand for RAGE, a major receptor of innate immunity stimulating inflammation responses including the pathogenesis of cerebral ischemia/reperfusion (I/R) injury. Blocking the HMGB1/RAGE axis offers a therapeutic approach to treating these inflammatory conditions.

Development of Functional Chimeric Nanoparticles by Membrane Fusion of Small Extracellular Vesicles and Drug-Encapsulated Liposomes.

Since small extracellular vesicle (sEVs) are involved in cell-to-cell communication via transfer of certain bioactive molecules and have the capability to overcome biological barriers against drug transport, their use as a drug delivery system (DDS) has been demonstrated in treatment of a diverse range of diseases. However, some issues in drug encapsulation have been pointed out, including low encapsulation efficiency and poor reproducibility. It was previously reported that liposomes containing phosphatidylserine (PS) can fuse together in the presence of calcium ion, which allows for drug encapsulation into the resultant liposomes (i.

Development of Edaravone Ionic Liquids and Their Application for the Treatment of Cerebral Ischemia/Reperfusion Injury.

Preparation of the ionic liquid (IL) form of active pharmaceutical ingredients (APIs), termed API-IL, has attracted attention because it can improve upon certain disadvantages of APIs, such as poor water solubility and low stability. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a clinically approved cerebroprotective agent against ischemic stroke and amyotrophic lateral sclerosis, while new formulations that enable improvement of its physicochemical properties and biodistribution are desired. Herein, we report a newly developed API-IL of edaravone (edaravone-IL), in which edaravone is used as an anionic molecule.

The Effect of Iontophoretic-Delivered Polyplex Vaccine on Melanoma Regression.

Although the strategy in cancer vaccination is to provide a therapeutic effect against an established tumor, there is an urgent need to develop prophylactic vaccines for non-viral cancers. In this study, we prepared polyplex nanoparticles through electrostatic interactions between a positively-charged modified tumor associated antigen, namely human derived melanoma gp100 peptide (KVPRNQDWL-RRRR), and a negatively charged cytosine-phosphate-guanosine motif (CpG-ODN) adjuvant. We previously demonstrated successful transdermal delivery of various hydrophilic macromolecules by iontophoresis (IP) using weak electricity.

One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique.

The use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation of therapeutic agents with superior efficiency and scalability is required. Herein, we used RAW264 macrophage cell-derived exosomes (RAW-Exos) and demonstrated that high-pressure homogenization (HPH) using a microfluidizer decreased their particle size without changing their morphology, the amount of exosomal marker proteins, and cellular uptake efficiency into RAW264 and colon-26 cancer cells.

Biomimetic Nanoparticle Drug Delivery Systems to Overcome Biological Barriers for Therapeutic Applications.

Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.

Enhancement of cerebroprotective effects of lipid nanoparticles encapsulating FK506 on cerebral ischemia/reperfusion injury by particle size regulation.

Delivery of cerebroprotective agents using liposomes has been demonstrated to be useful for treating cerebral ischemia/reperfusion (I/R) injury. We previously reported that intravenous administration of liposomes with diameters of 100 nm showed higher accumulation in the I/R region compared with larger liposomes (>200 nm) by passage through the disintegrated blood-brain barrier, suggesting a size-dependence for liposome-mediated drug delivery. Based on these findings, we hypothesized that regulation of liposomal particle size (<100 nm) may enhance the therapeutic efficacy of encapsulated drugs on cerebral I/R injury.

Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke.

Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells.

Iontophoresis-mediated direct delivery of nucleic acid therapeutics, without use of carriers, to internal organs via non-blood circulatory pathways.

Nanoparticle drug carriers have been employed to achieve systemic delivery of nucleic acid therapeutics, including small interfering RNA (siRNA); however, non-specific distribution and immune-related events often cause undesired adverse effects. Thus, there is a need for a new technology capable of specifically delivering nucleic acid therapeutics to desired sites. We demonstrated the utility of iontophoresis (IP) using weak electric current (0.

Effective Anticancer Therapy by Combination of Nanoparticles Encapsulating Chemotherapeutic Agents and Weak Electric Current.

Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J.

[Development of Biomembrane-mimetic Nanoparticles for the Treatment of Ischemic Stroke].

Increase in vascular permeability of the blood-brain barrier (BBB) is a distinct pathology following ischemic stroke. In previous studies, we demonstrated that liposomal drug delivery system (DDS)-based delivery of neuroprotectants is useful for treating cerebral ischemia/reperfusion injury. Additionally, our previous studies reported that combination therapy with liposomal fasudil plus tissue plasminogen activator (t-PA), a thrombolytic agent, brings about decrease in the risk of t-PA-derived cerebral hemorrhage and prolong the therapeutic time window of t-PA for treating acute ischemic stroke.

A simple, fast, and orientation-controllable technology for preparing antibody-modified liposomes.

Modification with antibodies is a useful strategy for the delivery of nanoparticles to target cells. However, the complexity of the required chemical modifications makes them time-consuming and low efficiency, and the orientation of the antibody is challenging to control. To develop a simple, fast, effective, and orientation-controllable technology, we employed staphylococcal protein A, which can bind to the Fc region of antibodies, as a tool for conjugating antibodies to nanoparticles.

Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-κB decoy oligodeoxynucleotide.

Transdermal delivery of nucleic acid therapeutics has been demonstrated to be effective for psoriasis treatment. We previously reported the utility of iontophoresis (IP) using weak electric current (0.3-0.

Suppression of Lipid Accumulation in 3T3-L1 Adipocytes by α-Tocopheryl Succinate.

Obesity is a pathological state related to various lifestyle-related diseases, such as diabetes and dyslipidemia, that may be prevented through the development of anti-obesity treatments. Lipid accumulation in cells could be affected by vitamin E ester α-tocopheryl succinate (TS), which has various biological activities, such as anti-cancer effect, via activation of cell signaling pathways, although the antioxidative activity of TS is lost due to esterification of the phenolic OH group. In this study, we found for the first time that TS significantly suppressed lipid accumulation in mouse 3T3-L1 adipocytes.

Weak Electric Current Treatment to Artificially Enhance Vascular Permeability in Embryonated Chicken Eggs.

Technologies that overcome the barrier presented by vascular endothelial cells are needed to facilitate targeted delivery of drugs into tissue parenchyma by intravenous administration. We previously reported that weak electric current treatment (ET: 0.3-0.

Leukocyte-Mimetic Liposomes Penetrate Into Tumor Spheroids and Suppress Spheroid Growth by Encapsulated Doxorubicin.

As leukocytes can penetrate into deep regions of a tumor mass, leukocyte-mimetic liposomes (LM-Lipo) containing leukocyte membrane proteins are also expected to penetrate into tumors by exerting properties of those membrane proteins. The aim of the present study was to examine whether LM-Lipo, which were recently demonstrated to actively pass through inflamed endothelial layers, can penetrate into tumor spheroids, and to investigate the potential of LM-Lipo for use as an anticancer drug carrier. We prepared LM-Lipo via intermembrane protein transfer from human leukemia cells; transfer of leukocyte membrane proteins onto the liposomes was determined by Western blotting.

Release rate is a key variable affecting the therapeutic effectiveness of liposomal fasudil for the treatment of cerebral ischemia/reperfusion injury.

Liposomal fasudil as a treatment for cerebral ischemia/reperfusion (I/R) injury has been demonstrated to be effective in animal models due to the high accumulation of liposomes in damaged brain tissue. However, it is still unclear what effect drug release rate has on the treatment of I/R injury, where pathology progresses dramatically in a short time. In the present study, we assessed four formulations of liposomal fasudil.

Protective Effect of Antioxidative Liposomes Co-encapsulating Astaxanthin and Capsaicin on CCl-Induced Liver Injury.

Our previous study reported that co-encapsulation of potent antioxidants astaxanthin (Asx) and capsaisin (Cap) into liposomes brought about synergistically higher antioxidative activity than the calculated additive activity of each single antioxidant encapsulating liposome. Based on the previous computational chemistry analysis, the synergistic effect was revealed to be resulted from intermolecular interactions between Asx, especially 3R,3'R-form of Asx stereoisomer (Asx-R), and Cap, by which changes of electronic states of the polyene moiety of Asx-R were induced. Although liposomes co-encapsulating Asx-R and Cap (Asx-R/Cap-Lipo) at an optimal ratio clearly showed synergistic antioxidative activity in vitro, it is unclear whether the effective antioxidative activity derived from intermolecular interaction between Asx-R and Cap is also exerted in vivo.

[Development of DDS Actively to Overcome the Blood-brain Barrier in the Region of Ischemic Stroke].

We previously showed that increased permeability of the blood-brain barrier (BBB) after ischemic stroke enables extravasation of nano-sized liposomes and accumulation in the ischemic region, and that delivery of neuroprotective agents using liposomal drug delivery systems (DDS) is applicable for treating cerebral ischemia/reperfusion (I/R) injury. However, entry of liposomes into the brain parenchyma was limited in the early stages after I/R possibly due to microvascular dysfunction induced by pathological progression. As such, new approaches to overcome the BBB are needed.