Light-Induced Conjugation of Inorganic Phosphate and Sulfate with Aminocyclobutenediones under Aqueous Conditions.

Phosphate and sulfate groups play an important role in controlling the physical properties of biomolecules and artificial materials. However, despite their significance, the incorporation of phosphate or sulfate groups into aqueous organic compounds using non-enzymatic methods has been unprecedented. In this study, we have successfully conjugated inorganic phosphate and sulfate with aminocyclobutenedione derivatives via photochemical reactions under aqueous conditions.

Choice of organic solvent affects function of mRNA-LNP; pyridine produces highly functional mRNA-LNP.

Lipid nanoparticles (LNPs) are well-known nanocarriers for mRNA delivery. mRNA-encapsulated LNPs (mRNA-LNPs) are prepared by alcohol dilution (broadly defined as solvent dilution) method, in which mRNA dissolved in acidic buffer is mixed with lipid dissolved in an organic solvent. Ethanol is the most commonly used organic solvent for dissolving lipids during the preparation of mRNA-LNPs.

Photothermal therapeutic effect by gold nanostars/extracellular vesicles nanocomplex on melanoma cells.

Photothermal therapy (PTT) is a method for treating cancer using the heat generated by light irradiation, often in combination with light-absorbing materials. Efficient PTT requires a drug delivery system to deliver light-absorbing materials to cancerous tissues. Gold nanostars (GNSs) enable efficient PTT through absorbing long-wavelength light.

Stable and inhalable powder formulation of mRNA-LNPs using pH-modified spray-freeze drying.

A powder formulation for mucosal administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is expected to be useful for respiratory diseases. Although freeze-drying is widely used to obtain solid formulations of mRNA-LNPs, highly hydrosoluble cryoprotectants, such as sucrose are necessary. However, sucrose is not a suitable excipient for inhalation powders because of its hygroscopic and deliquescence properties.

Development of Hollow Gold Nanoparticles for Photothermal Therapy and Their Cytotoxic Effect on a Glioma Cell Line When Combined with Copper Diethyldithiocarbamate.

Gold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95-135 nm in diameter with a light absorbance range of approximately 600-720 nm.

Optimization, cellular uptake, and in vivo evaluation of Eudragit S100-coated bile salt-containing liposomes for oral colonic delivery of 5-aminosalicylic acid.

Eudragit S100-coated bile salt-containing liposomes were prepared and optimized by experimenting with different variables, including bile salt type and concentration, and the method of incorporation into liposomes using a model hydrophilic compound, 5-aminosalicylic acid (5-ASA). After optimizing the formulation, cellular uptake, and animal pharmacokinetic experiments were performed. The inclusion of sodium glycocholate (SG) into liposomes decreased liposome particle size and entrapment efficiency significantly but had no effect on zeta potential.

Fabrication of 3D-Printed Contact Lens Composed of Polyethylene Glycol Diacrylate for Controlled Release of Azithromycin.

Since three-dimensional (3D)-printed tablets were approved by the United States Food and Drug Administration (FDA), 3D printing technology has garnered increasing interest for the fabrication of medical and pharmaceutical devices. With various dosing devices being designed for manufacture by 3D printing, 3D-printed ophthalmic formulations to release drugs have been one such target of investigation. In the current study, 3D-printed contact lenses designed for the controlled release of the antibiotic azithromycin were produced by vat photopolymerization, and the effect of the printer ink composition and a second curing process was investigated.

Fabrication and Characterization of Antibody-Loaded Cationic Porous PLGA Microparticles for Sustained Antibody Release.

Poly lactic-co-glycolic acid (PLGA) microparticles have been formulated to allow the sustained release of numerous drugs, including antibodies. It is well-known that antibodies are susceptible to chemical and physical stress; therefore, it is necessary to be loaded on PLGA microparticles under mild conditions. In the present study, we constructed cationic porous PLGA microparticles that could be electrostatically adsorbed with infliximab as a model antibody.

[Development and Evaluation of Brain-targeted Drug and Gene Delivery System].

New drug modalities such as nucleic acid, gene, cells, and nanoparticles are expected for treating refractory diseases. However, these drugs have larger size and low cell membrane permeability; therefore, drug delivery systems (DDS) are essential for delivery to the intended site at the organ and cellular level. In case of the brain, drug migration to the brain from blood circulation is extremely limited by the blood-brain barrier (BBB).

Improved drug transfer into brain tissue via the "nose-to-brain" approach using suspension or powder formulations based on the amorphous solid dispersion technique.

Intranasal administration has attracted increasing attention as a drug delivery approach based on nose-to-brain drug delivery from the nasal cavity to brain tissue directly, bypassing the blood-brain barrier. However, application of the method to poorly water-soluble drugs is potentially limited due to low aqueous solubility and dissolution, which can hinder drug transfer to brain tissue. In the present study, we focused on an amorphous solid dispersion (ASD) technique to improve drug dissolution.

Arbekacin-Loaded Inhalable Nanocomposite Particles Specific to Pseudomonas aeruginosa Prepared Using a Two-Solution Mixing-Type Spray Nozzle.

Hospital-acquired pneumonia is an important infectious disease that requires special management and therapy for patients with compromised immunity, as opportunistic infections with microorganisms such as Pseudomonas aeruginosa can be fatal. Nanoparticle-based drug delivery to lung tissue provides several advantages in the treatment of respiratory diseases. In the current study, inhalable nanocomposite particles consisting of microparticles containing solid-state arbekacin (ABK) nanoparticles coated with hydrophobic surfactant (ABK-SD nanoparticles) were prepared using a spray dryer equipped with a two-solution mixing-type spray nozzle we previously developed.

Stem Cell Therapy for Acute/Subacute Ischemic Stroke with a Focus on Intraarterial Stem Cell Transplantation: From Basic Research to Clinical Trials.

Stem cell therapy for ischemic stroke holds great promise for the treatment of neurological impairment and has moved from the laboratory into early clinical trials. The mechanism of action of stem cell therapy includes the bystander effect and cell replacement. The bystander effect plays an important role in the acute to subacute phase, and cell replacement plays an important role in the subacute to chronic phase.

Contamination-Free Milling of Ketoprofen Nanoparticles Using Mannitol Medium and Hoover Automatic Muller: Optimization of Effective Design of Experiment.

Wear-resistant polymers and ceramics-based media have been used to pulverize the bulk powder of poorly water-soluble drugs to nanoscale size in conventional milling; however, contamination of such media is still an issue in the context of drug formulation manufacturing. In the present study, we developed a novel method for pulverizing the particles of a poorly water-soluble drug, ketoprofen, to nanoscale size by mixing mannitol and polypropylene glycol as a safe pulverizing medium. The ketoprofen nanoparticles were prepared using a Hoover automatic muller, equipment that traditionally has been used for the mixing of paint and ink.

Fabrication of Mucoadhesive Films Containing Pharmaceutical Ionic Liquid and Eudragit Polymer Using Pressure-Assisted Microsyringe-Type 3D Printer for Treating Oral Mucositis.

Oral mucositis in the oral cavity, caused by radiation therapy and chemotherapy, requires personalized care and therapy due to variations in the lesions of patients. In the present study, we fabricated a model of personalized oral film containing an ibuprofen/lidocaine ionic liquid (IL) for patients with oral mucositis using a pressure-assisted microsyringe-type 3D printer at room temperature. The film contained a Eudragit polymer (L100, EPO, or RSPO) to make the film solid, and the printer ink was composed of organo ink (organic solvent to dissolve both drugs and the Eudragit polymer).

Preparation, Characterization and In Vitro Evaluation of Eudragit S100-Coated Bile Salt-Containing Liposomes for Oral Colonic Delivery of Budesonide.

The aim of this study was to prepare a liposomal formulation of a model drug (budesonide) for colonic delivery by incorporating a bile salt (sodium glycocholate, SGC) into liposomes followed by coating with a pH-responsive polymer (Eudragit S100, ES100). The role of the SGC is to protect the liposome from the emulsifying effect of physiological bile salts, while that of ES100 is to protect the liposomes from regions of high acidity and enzymatic activity in the stomach and small intestine. Vesicles containing SGC were prepared by two preparation methods (sonication and extrusion), and then coated by ES100 (ES100-SGC-Lip).

Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain.

Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability.

Recent advances in lipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based therapeutics.

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established.

Suppression of Peritoneal Fibrosis by Sonoporation of Hepatocyte Growth Factor Gene-Encoding Plasmid DNA in Mice.

Gene therapy is expected to be used for the treatment of peritoneal fibrosis, which is a serious problem associated with long-term peritoneal dialysis. Hepatocyte growth factor (HGF) is a well-known anti-fibrotic gene. We developed an ultrasound and nanobubble-mediated (sonoporation) gene transfection system, which selectively targets peritoneal tissues.

Recent Strategies for Targeted Brain Drug Delivery.

Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired.

Nanobubble Mediated Gene Delivery in Conjunction With a Hand-Held Ultrasound Scanner.

Recent research has revealed that nanobubbles (NBs) can be an effective tool for gene transfection in conjunction with therapeutic ultrasound (US). However, an approach to apply commercially available hand-held diagnostic US scanners for this purpose has not been evaluated as of now. In the present study, we first compared , the efficiency of gene transfer (pCMV-Luciferase) with lipid-based and albumin-based NBs irradiated by therapeutic US (1MHz, 5.

Ultrasound-responsive nanobubble-mediated gene transfection in the cerebroventricular region by intracerebroventricular administration in mice.

Aim: Intracerebroventricular (ICV) administration of ultrasound-responsive bubbles and cranial ultrasound irradiation is reported as a transfection system for the cerebroventricular region. This study aimed to characterize the transfection system with respect to transfection efficiency, spatial distribution of transgene expression, and safety.

Methods: Plasmid DNA was transfected to mouse brain by ICV injection of ultrasound-responsive nanobubbles, followed by ultrasound irradiation to brain.

Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method.

Introduction: We previously developed anionic ternary bubble lipopolyplexes, an ultrasound-responsive carrier, expecting safe and efficient gene transfection. However, bubble lipopolyplexes have a low capacity for echo gas (CF) encapsulation (EGE) in nonionic solution such as 5% glucose. On the other hand, we were able to prepare bubble lipopolyplexes by inserting phosphate-buffered saline before CF encapsulation.

Evaluation of the targeted delivery of 5-fluorouracil and ascorbic acid into the brain with ultrasound-responsive nanobubbles.

Recently, ultrasound-induced drug delivery into the brain using bubble formulations has been developed. After the brain delivery, however, the information on pharmacokinetics of hydrophilic drugs in the brain is lacking. In this study, to clarify the time-course pharmacokinetics of hydrophilic drugs, we used a brain microdialysis method.