CSF1R inhibitor PLX3397 depletes microglia in Mongolian gerbil Meriones unguiculatus, but not in syrian hamster Mesocricetus auratus.

Microglia are the residential immune cells in the central nervous system. Their roles as innate immune cells and regulators of synaptic remodeling are critical to the development and the maintenance of the brain. Numerous studies have depleted microglia to elucidate their involvement in healthy and pathological conditions.

Methyl vinyl ketone impairs spatial memory and activates hippocampal glial cells in mice.

Memory is a fundamental brain function that can be affected by a variety of external factors including environmental pollutants. One of these pollutants is methyl vinyl ketone (MVK), a hazardous substance found in cigarettes, industrial wastes, and car exhaust. Humans can be exposed to MVK under many circumstances; however, it is unclear whether MVK affects higher-order brain functions such as memory.

Effect of PEG anchor in PEGylation of folate-modified cationic liposomes with PEG-derivatives on systemic siRNA delivery into the Tumor.

In this study, we prepared small interfering RNA (siRNA)/cationic liposome complexes (lipoplexes) modified with folate (FA)-polyethylene glycol (PEG, MW 2000, 3400 or 5000)-1,2-distearoyl--glycero-3-phosphoethanolamine (DSPE) to facilitate their uptake into tumor cells folate receptor (FR), and with PEG-cholesterol (PEG-Chol) or PEG-chondroitin sulfate conjugate (PEG-CS), to enhance their systemic stability. Among the FA-PEG-modified siRNA lipoplexes, 0.5 mol% FA-PEG-DSPE-modified lipoplexes with 2.

[Effect of Storage of Tulobuterol Tapes after Package Opening and Liner Peeling on Their Formulation Properties].

Although tulobuterol tape is provided to patients in an inner package, information regarding the stability of the tape after opening the packaging may be requested by patients. This study was performed to generate underlying data on the storage stability after package opening or liner peeling with package opening. Tulobuterol tapes were stored at 25℃, 60% relative humidity (RH); 40℃, 75%RH; or in a refrigerator (2-4℃, 10-30%RH) for 1 day or 3 days.

Preparation and evaluation of fast-dissolving films of etilefrine hydrochloride for practical buccal dosing.

Etilefrine hydrochloride (ET) is an important drug in the treatment of hypotension, and parenteral injections and oral tablets are the conventional dosage forms. However, parenteral injections may cause abnormally high plasma levels as well as pain and necrosis, and oral tablets undergo first-pass metabolism. Although fast-dissolving buccal tablets were previously reported, the initial absorption rate was a little slow and the plasma levels were varied extensively.

Targeting potential of alginate-glycyl-prednisolone conjugate nanogel to inflamed joints in rats with adjuvant-induced arthritis.

The efficacy of alginate-glycyl-prednisolone conjugate nanogel (AL-GP-NG) was previously reported to be better than that of prednisolone (PD) alone in arthritic rats. In the present study, novel AL-GP-NG was prepared and its targeting potential was investigated. AL-GP-NG with a PD content of 6.

Preparation and evaluation of conjugate nanogels of glycyl-prednisolone with natural anionic polysaccharides as anti-arthritic delivery systems.

Although prednisolone (PD) is used as an anti-arthritis drug due to its rapid and strong anti-inflammatory potential, its frequent and large dosing often brings about adverse effects. Therefore, targeting therapy has attracted increasing attention to overcome such adverse effects. In the present study, nanogels (NGs) composed of macromolecule-PD conjugates were developed as a novel targeting delivery system, and their anti-inflammatory potential was examined.

Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution in mice.

Polyethylene glycol (PEG)‑modifications (PEGylations) of cationic liposome/small interfering RNA complexes (siRNA lipoplexes) can enhance their systemic stability. The present study determined the effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution after intravenous injection. Three types of dialkyl or trialkyl cationic lipids were used in the current study for the preparation of cationic liposomes.

Preliminary Investigation of the Usability Characteristics Required for Wound Management Products by Semi-Structural Interview of Medical Staff.

Consideration of drug usability characteristics is important during the design process. Although many wound management products have been developed in recent years, there are few studies on their usability. We investigated the needs and characteristics of wound management products required by medical professionals, so as to consider these in future development projects.

Preparation of orally fast-dissolving tablets of etilefrine hydrochloride to achieve efficient absorption.

Etilefrine hydrochloride (ET) is commonly used in the treatment of hypotension in dosage forms of oral tablets and parenteral injections. However, oral tablets only temporarily achieve high plasma levels and have low bioavailability (BA), while intravenous injections may cause pain and necrosis around administration sites. In an attempt to overcome these limitations, the buccal delivery of ET using oral droplets has been investigated.

Formulation Development of Mucoadhesive Microparticle-Laden Gels for Oral Mucositis: An In Vitro and In Vivo Study.

In order to relieve pain due to oral mucositis, we attempted to develop mucoadhesive microparticles containing indomethacin (IM) and gel preparations with IM microparticles that can be applied to the oral cavity. The mucoadhesive microparticles were prepared with a simple composition consisting of IM and polyvinyl alcohol (PVA). Two kinds of PVA with different block properties were used, and microparticles were prepared by heating-filtration and mixing-drying.

Development of Morin-Loaded Nanoemulsions Containing Various Polymers; Role of Polymers in Formulation Properties and Bioavailability.

Emulsions for oral delivery are not suitable for sustained drug absorption because such preparations diffuse rapidly in the gastrointestinal (GI) tract after oral administration. In order to generate sustained drug absorption and increase oral bioavailability, various polymers were added to a morin (MO) nanoemulsion to improve retention in the GI tract and alter the surface properties of oil droplets in the nanoemulsion. The influence of these polymers on the formulation properties was investigated.

Nanogels of a Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Release Behavior, Gastrointestinal Distribution, and Systemic Absorption.

Recently, the potential of nanoparticles (NPs) in ulcerative colitis (UC) therapy has been increasingly demonstrated. Namely, anionic NPs have been found to be accumulated efficiently to the UC damaged area due to epithelial enhanced permeability and retention (eEPR) effect. Previously, a novel anionic nanogel system (NG(S)) was prepared, and evaluated for the efficacy and toxicity.

Gene delivery into hepatic cells with ternary complexes of plasmid DNA, cationic liposomes and apolipoprotein E-derived peptide.

Cationic liposomes containing a cationic lipid, such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), have often been used for the transduction of plasmid DNA (pDNA) . However, such liposomes induce gene expression primarily in the lungs after intravenous injection. To improve the delivery of cationic liposomes/pDNA complexes (pDNA lipoplexes) to the liver by intravenous administration, the current study synthesized two apolipoprotein E (ApoE)-derived peptides, dApoE-R9 and ApoE-F-R9, for liver targeting via certain ApoE receptors, including the low-density lipoprotein receptor.

Novel Xyloglucan Sheet for the Treatment of Deep Wounds: Preparation, Physicochemical Characteristics, and in Vivo Healing Effects.

In the present study, a novel wound dressing made of xyloglucan (Xyl)-sucrose (Suc) hydrogel was developed for the treatment of deep wounds including pressure ulcers. The dressing was prepared by casing an aqueous solution of Xyl and sugar and then warming, and a hydrogel sheet was obtained. The in vitro characteristics of these sheets, such as their strength, extensibility, water content, adhesion potential, and water absorption, were examined.

Nanogels of Succinylated Glycol Chitosan-Succinyl Prednisolone Conjugate: Preparation, In Vitro Characteristics and Therapeutic Potential.

A novel anionic nanogel system was prepared using succinylated glycol chitosan-succinyl prednisolone conjugate (S-GCh-SP). The nanogel, named NG(S), was evaluated in vitro and in vivo. S-GCh-SP formed a nanogel via the aggregation of hydrophobic prednisolone (PD) moieties and the introduced succinyl groups contributed to the negative surface charge of the nanogel.

Preparation of Chondroitin Sulfate-Glycyl-Prednisolone Conjugate Nanogel and Its Efficacy in Rats with Ulcerative Colitis.

A conjugate between chondroitin sulfate (CS) and glycyl-prednisolone (GP), named CS-GP, was produced by carbodiimide coupling at a high GP/CS ratio. CS-GP was not water-soluble and gave a nanogel (NG) in aqueous solution. Two types of nanogels, NG(I) and NG(II), with prednisolone (PD) contents of 5.

Effects of cationic lipids in cationic liposomes and disaccharides in the freeze-drying of siRNA lipoplexes on gene silencing in cells by reverse transfection.

RNA interference is a promising technology to inhibit the production of target proteins, and screening with synthetic small interfering RNA (siRNA) libraries has become a crucial research tool used to study gene function in cells. Reverse (Rev) transfection with freeze-dried siRNA/cationic liposome complexes (siRNA lipoplexes) can simplify and speed up siRNA transfection without the preparation of siRNA lipoplexes just before transfection. In this study, we examined the effects of cationic lipids in cationic liposomes and disaccharides in freeze-drying of siRNA lipoplexes on gene silencing in cells by Rev-transfection.

Development of microparticles coated with poly-γ-glutamic acid to improve oral absorption of a poorly water-soluble drug.

Novel microparticles coated with poly-γ-glutamic acid (PGA) were developed to improve the oral absorption of indomethacin (IM), a poorly water-soluble drug. Microparticles containing γ-IM (IM-PGA) or crystal polymorph α-IM (IM-PGA) were prepared. Additionally, microparticles were prepared containing α-IM without PGA (IM without PGA).

Effect of Cationic Lipid Type in Folate-PEG-Modified Cationic Liposomes on Folate Receptor-Mediated siRNA Transfection in Tumor Cells.

In this study, we examined the effect of cationic lipid type in folate (FA)-polyethylene glycol (PEG)-modified cationic liposomes on gene-silencing effects in tumor cells using cationic liposomes/siRNA complexes (siRNA lipoplexes). We used three types of cationic cholesterol derivatives, cholesteryl (3-((2-hydroxyethyl)amino)propyl)carbamate hydroiodide (HAPC-Chol), -(2-(2-hydroxyethylamino)ethyl)cholesteryl-3-carboxamide (OH-Chol), and cholesteryl (2-((2-hydroxyethyl)amino)ethyl)carbamate (OH-C-Chol), and we prepared three types of FA-PEG-modified siRNA lipoplexes. The modification of cationic liposomes with 1-2 mol % PEG-lipid abolished the gene-silencing effect in human nasopharyngeal tumor KB cells, which overexpress the FA receptor (FR).

Absorption behavior of etilefrine after buccal administration in rats.

Etilefrine hydrochloride (ET-HCl) is used in the treatment of hypotension. Dosage forms of orally administered tablets and parenteral injections are clinically available, but exhibit unfavorable characteristics, including cardiac toxicity, headaches, and damage at the injection site for the parenteral dosage form, and initially high plasma levels, fast elimination, and first-pass effects for its oral administration. Therefore, the buccal application of ET-HCl was herein investigated as an alternative to conventional administration routes.

Effect of cationic lipid in cationic liposomes on siRNA delivery into the lung by intravenous injection of cationic lipoplex.

Cationic liposomes composed of dialkyl cationic lipid such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) can efficiently deliver siRNA to the lungs following the intravenous injection of cationic liposome/siRNA complexes (lipoplexes). In this study, we examined the effect of cationic lipid of cationic liposomes on siRNA delivery to the lungs after intravenous injection. We used six kinds of cationic cholesterol derivatives and 11 kinds of dialkyl or trialkyl cationic lipids as cationic lipids, and prepared 17 kinds of cationic liposomes composed of a cationic lipid and 1,2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) for evaluation of siRNA biodistribution and in vivo gene silencing effects.

Influence of Polysorbate 60 on Formulation Properties and Bioavailability of Morin-Loaded Nanoemulsions with and without Low-Saponification-Degree Polyvinyl Alcohol.

The aim of the present study was to investigate the influence of polysorbate 60 (Tween 60) on the development of morin-loaded nanoemulsions to improve the oral bioavailability of morin. Nanoemulsions were prepared using Tween 60 and polyvinyl alcohol (PVA) as emulsifiers, and medium chain triglycerides (MCT) as the lipid base. Low-saponification-degree PVA (LL-810) was also added to stabilize dispersed droplets.

Therapeutic effects of protein kinase N3 small interfering RNA and doxorubicin combination therapy on liver and lung metastases.

It has been reported that suppression of protein kinase N3 (PKN3) expression in vascular and lymphatic endothelial cells results in the inhibition of tumor progression and lymph node metastasis formation. The present study investigated whether combination therapy of small interfering RNA (siRNA) against PKN3 and doxorubicin (DXR) could increase therapeutic efficacy against liver and lung metastases. transfection of PKN3 siRNA into PKN3-positive MDA-MB-231, LLC, and Colon 26 cells and PKN3-negative MCF-7 cells did not inhibit cell growth and did not increase sensitivity to DXR.

Evaluation of and therapeutic antitumor efficacy of transduction of polo-like kinase 1 and heat shock transcription factor 1 small interfering RNA.

Mitotic progression is regulated by the phosphorylation of heat shock transcription factor 1 (HSF1) by polo-like kinase 1 (PLK1); however, this interaction is often deregulated in tumors. High expression levels of PLK1 and HSF1 have been observed in various types of human cancer. In the present study, it was investigated whether small interfering (si)RNA against PLK1 or HSF1 could suppress tumor growth and .