-
International Journal of Nanomedicine 2024Angiogenesis is a physiological process of forming new blood vessels that has pathological importance in seemingly unrelated illnesses like cancer, diabetes, and various... (Review)
Review
Angiogenesis is a physiological process of forming new blood vessels that has pathological importance in seemingly unrelated illnesses like cancer, diabetes, and various inflammatory diseases. Treatment targeting angiogenesis has shown promise for these types of diseases, but current anti-angiogenic agents have critical limitations in delivery and side-effects. This necessitates exploration of alternative approaches like biomolecule-based drugs. Proteins, lipids, and oligonucleotides have recently become popular in biomedicine, specifically as biocompatible components of therapeutic drugs. Their excellent bioavailability and potential bioactive and immunogenic properties make them prime candidates for drug discovery or drug delivery systems. Lipid-based liposomes have become standard vehicles for targeted nanoparticle (NP) delivery, while protein and nucleotide NPs show promise for environment-sensitive delivery as smart NPs. Their therapeutic applications have initially been hampered by short circulation times and difficulty of fabrication but recent developments in nanofabrication and NP engineering have found ways to circumvent these disadvantages, vastly improving the practicality of biomolecular NPs. In this review, we are going to briefly discuss how biomolecule-based NPs have improved anti-angiogenesis-based therapy.
Topics: Humans; Angiogenesis Inhibitors; Theranostic Nanomedicine; Neovascularization, Pathologic; Animals; Liposomes; Nanostructures; Neoplasms; Drug Delivery Systems; Oligonucleotides; Proteins; Lipids; Nanoparticles
PubMed: 38946886
DOI: 10.2147/IJN.S459928 -
International Journal of Nanomedicine 2024Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite...
BACKGROUND
Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration.
METHODS
Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models.
RESULTS
The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups.
CONCLUSION
Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.
Topics: Alginates; Animals; Bone Morphogenetic Protein 7; Gelatin; Tissue Engineering; Hydrogels; Durapatite; Osteogenesis; Rats; Bone Regeneration; Tissue Scaffolds; Rats, Sprague-Dawley; Methacrylates; Male; Humans; Bone and Bones
PubMed: 38946885
DOI: 10.2147/IJN.S461996 -
International Journal of Nanomedicine 2024It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery...
BACKGROUND
It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research.
METHODS
First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo.
RESULTS
CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 μg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent.
CONCLUSION
Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.
Topics: Flavanones; Animals; Osteoclasts; Bone Regeneration; Silicon Dioxide; Hydrogen-Ion Concentration; Nanoparticles; Rats; Mice; Rats, Sprague-Dawley; Chitosan; Male; Drug Liberation; Porosity; Drug Carriers; Bone Resorption; RAW 264.7 Cells; Drug Delivery Systems; Cell Differentiation
PubMed: 38946884
DOI: 10.2147/IJN.S456545 -
Physiological Reports Jul 2024The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl)-induced...
Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.
The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl + Catechin), and treatment group 2 (AlCl + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.
Topics: Animals; Catechin; Aluminum Chloride; Chitosan; Alginates; Male; Rats, Wistar; Alzheimer Disease; Rats; Nanoparticles; Administration, Oral; Cognition; Acetylcholinesterase; Maze Learning; Hippocampus; Disease Models, Animal; Antioxidants; Oxidative Stress; Drug Carriers
PubMed: 38946616
DOI: 10.14814/phy2.16095 -
Signal Transduction and Targeted Therapy Jul 2024The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this... (Review)
Review
The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.
Topics: Hydrogels; Humans; Cell- and Tissue-Based Therapy; Drug Delivery Systems; Biocompatible Materials; Animals; Tissue Engineering
PubMed: 38945949
DOI: 10.1038/s41392-024-01852-x -
Chemical & Pharmaceutical Bulletin 2024In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry...
In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.
Topics: Tablets; Particle Size; Drug Compounding; Powders; Stearic Acids; Tensile Strength; Excipients; Solubility
PubMed: 38945947
DOI: 10.1248/cpb.c23-00801 -
Journal of Oleo Science 2024This comprehensive review offers a chemical analysis of cutting fluids, delving into both their formulation and deformulation processes. The study covers a wide spectrum... (Review)
Review
This comprehensive review offers a chemical analysis of cutting fluids, delving into both their formulation and deformulation processes. The study covers a wide spectrum of cutting fluid formulations, ranging from simple compositions predominantly comprising oils, whether mineral or vegetable, to emulsions. The latter involves the integration of surfactants, encompassing both nonionic and anionic types, along with a diverse array of additives. Concerning oils, the current trend leans towards the use of vegetable oils instead of mineral oils for environmental reasons. As vegetable oils are more prone to oxidation, chemical alterations, the addition of antioxidant may be necessary. The chemical aspects of the different compounds are scrutinized, in order to understand the role of each component and its impact on the fluid's lubricating, cooling, anti-wear, and anti-corrosion properties. Furthermore, the review explores the deformulation methodologies employed to dissect cutting fluids. This process involves a two-step approach: separating the aqueous and organic phases of the emulsions by physical or chemical treatments, and subsequently conducting a detailed analysis of each to identify the compounds. Several analytical techniques, including spectrometric or chromatographic, can be employed simultaneously to reveal the chemical structures of samples. This review aims to contribute to the improvement of waste treatment stemming from cutting fluids. By gathering extensive information about the formulation, deformulation, and chemistry of the ingredients, there is a potential to enhance the waste management and disposal effectively.
Topics: Emulsions; Surface-Active Agents; Plant Oils; Mineral Oil; Antioxidants; Oxidation-Reduction; Lubrication; Lubricants; Chemical Phenomena
PubMed: 38945922
DOI: 10.5650/jos.ess24068 -
Journal of Oleo Science 2024This paper reports a novel α-gel formulation technology referred to as polymer complexed lamella (PCL) that uses hydroxypropyl methyl cellulose (HPMC) and glycerol. The...
This paper reports a novel α-gel formulation technology referred to as polymer complexed lamella (PCL) that uses hydroxypropyl methyl cellulose (HPMC) and glycerol. The PCL method suppressed lipid crystallization even after drying. This effect was maximized by the addition of HPMC and glycerol at high temperature. HPMC and lipids coexisted when mixed at high temperature, which decreased the mobility of HPMC, an effect that was enhanced by the strong interaction of glycerol with HPMC. These results indicate that mixing of HPMC with glycerol directly regulates the lipid structure and suppresses crystallization. PCL also maintained the effect of occlusion related to the moisturization of skin, even if the membrane was repeatedly bent such as in facial expressions.
Topics: Hypromellose Derivatives; Glycerol; Gels; Crystallization; Desiccation; Hot Temperature; Lipids; Polymers
PubMed: 38945921
DOI: 10.5650/jos.ess24053 -
Journal of Oleo Science 2024Herein, we evaluated friction dynamics of human skin treated with polyacrylic acid aqueous solutions or gel creams using a sinusoidal motion friction evaluation system...
Herein, we evaluated friction dynamics of human skin treated with polyacrylic acid aqueous solutions or gel creams using a sinusoidal motion friction evaluation system to demonstrate the effect of treatment with polymer aqueous solutions on human skin. A polymer aqueous solution or gel cream was applied to the inner forearms of 10 subjects to evaluate temporal changes in friction force under sinusoidal motion. Water content, skin viscoelasticity, and transepidermal water loss were also simultaneously measured to determine the effects on skin conditions. When human skin was treated with the polymer aqueous solution, the friction coefficient immediately after treatment was 0.69-0.99 and the delay time δ, a normalized parameter of the time difference in the delayed response of friction to the movement of the contact probe divided by the friction time T for one round trip, was 0.171-0.179, which was greater than that of untreated skin. This increase was caused by the swelling and softening of the stratum corneum caused by the penetration of water in the polymer aqueous solution, which increased true contact area between the skin and contact probe. A significant difference was observed in the friction coefficient of the skin immediately after treatment with different polymer aqueous solutions. Among polymers (P1-P4), P4, which has a low-salt resistance and low yield stress, had the lowest friction coefficient because of collapsing of the polymer network structures by shearing and reduced viscosity owing to salts on human skin. The skin treated with a gel cream also exhibited a greater friction coefficient than the untreated skin immediately after treatment and 90 min later. This phenomenon can be caused by the occlusive effect of the oil in the gel cream.
Topics: Humans; Friction; Water; Viscosity; Solutions; Acrylic Resins; Skin; Elasticity; Adult; Female; Male; Polymers; Skin Cream; Gels; Water Loss, Insensible
PubMed: 38945920
DOI: 10.5650/jos.ess24036 -
Nihon Yakurigaku Zasshi. Folia... 2024Ensitrelvir fumaric acid (Xocova hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint... (Review)
Review
Ensitrelvir fumaric acid (Xocova hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint research targeting SARS-CoV-2 3C-like (3CL) protease at an early stage and started clinical trials in July 2021. In February 2022, an application was filed for manufacture and sales approval for the indication of "SARS-CoV-2 infection,". Ensitrelvir recieved the first emergency regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan in November 2022, and has obtained standard approval in March 2024. This emergency approval was based on the confirmed safety in a Phase 2/3 study (T1221) conducted in Japan and other Asian countries (Korea and Vietnam) in patients with mild/moderate COVID-19 and the presumed efficacy in Phase 3 Part (SCORPIO-SR), and the standard approval is based on efficacy from the Phase 3 part. In the Phase 3 part, ensitrelvir administered orally 375/125 mg once daily for five days, in patients with irrespective of risk factors for severe complications and vaccination status, demonstrating a significant reduction vs placebo in the time to resolution of five typical Omicron-related symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and also showed a significant reduction in viral RNA on day 4 relative to placebo (P < 0.001). In the Phase 2/3 study, there were no serious adverse events or deaths, indicating good tolerability and safety. We hope that ensitrelvir will contribute as a new treatment option for patients suffering from COVID-19 symptoms.
Topics: Humans; COVID-19 Drug Treatment; SARS-CoV-2; Tablets; Clinical Trials as Topic; COVID-19; Antiviral Agents; Treatment Outcome; Fumarates; Indazoles; Triazines; Triazoles
PubMed: 38945910
DOI: 10.1254/fpj.24017