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latively good.The rapid development of nanotechnology offers a variety of potential therapeutic strategies for cancer treatment. High atomic element nanomaterials are often utilized as radiosensitizers due to their unique photoelectric decay characteristics. Among them, gold nanoparticles (GNPs) are one of the most widely investigated and are considered to be an ideal radiosensitizers for radiotherapy due to their high X-ray absorption and unique physicochemical properties. Over the last few decades, multi-disciplinary studies have focused on the design and optimization of GNPs to achieve greater dosing capability and higher therapeutic effects and highlight potential mechanisms for radiosensitization of GNPs. Although the radiosensitizing potential of GNPs has been widely recognized, its clinical translation still faces many challenges. This review analyses the different roles of GNPs as radiosensitizers in cancer radiotherapy and summarizes recent advances. In addition, the underlying mechanisms of GNP radiosensitization, including physical, chemical and biological mechanisms are discussed, which may provide new directions for the optimization and clinical transformation of next-generation GNPs.
Polyimide (PI) exhibits good biocompatibility and high mechanical strength, but biological inertness that does not stimulate bone regeneration, while laponite possesses excellent bioactivity.
In this study, to improve the bioactivity of PI, nano-laponite ceramic (LC)-PI composites (LPCs) were fabricated by melt processing as implantable materials for bone repair.
The compressive strength, hydrophilicity, and surface roughness of LPCs with 40 w% LC content (LPC40s) were higher than LPC20s, and LPC20s higher than pure PI. In addition, no apatite mineralization occurred on PI, while apatite mineralized on LPCs in simulated body fluid. Compared with LPC20, more apatite deposited on LPC40, indicating good bioactivity. Moreover, the adhesion, proliferation, and alkaline phosphatase activity of rat bone mesenchymal stem cells on LPCs significantly increased with LC content increasing in vitro. Furthermore, the evaluations of animal experiments (micro-CT, histology, and pushout load) revealed that compared with LPC20 and PI, LPC40 significantly enhanced osteogenesis and osseointegration in vivo.
Incorporation of LC into PI obviously improved not only surface physicochemical properties but also biological properties of LPCs. LPC40 with high LC content displayed good biocompatibility and bioactivity, which markedly promoted osteogenesis and osseointegration. Therefore, with its superior biocompatibility and bioactivity, LPC40 could be an alternative candidate as an implant for orthopedic applications.
Incorporation of LC into PI obviously improved not only surface physicochemical properties but also biological properties of LPCs. LPC40 with high LC content displayed good biocompatibility and bioactivity, which markedly promoted osteogenesis and osseointegration. Therefore, with its superior biocompatibility and bioactivity, LPC40 could be an alternative candidate as an implant for orthopedic applications.
The trans-ocular barrier is a key factor limiting the therapeutic efficacy of triamcinolone acetonide. We developed a poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) surface modified respectively with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), chitosan oligosaccharide and trehalose. Determination of the drug/nanoparticles interactions, characterization of the nanoparticles, in vivo ocular compatibility tests, comparisons of their corneal permeability and their pharmacokinetics in aqueous humor were carried out.
All PLGA NPs were prepared by the single emulsion and evaporation method and the drug-nanoparticle interaction was studied. The physiochemical features and in vitro corneal permeability of NPs were characterized while the aqueous humor pharmacokinetics was performed to evaluate in vivo corneal permeability of NPs. Ocular compatibility of NPs was investigated through Draize and histopathological test.
The PLGA NPs with lactide/glycolide ratio of 5050 and small particle size (molecular weight 10 kDa) achieved optimal drug release and corneal permeability. Surface modification with different oligosaccharides resulted in uniform particle sizes and similar drug-nanoparticle interactions, although 2-HP-β-CD/PLGA NPs showed the highest entrapment efficiency. In vitro evaluation and aqueous humor pharmacokinetics further revealed that 2-HP-β-CD/PLGA NPs had greater trans-ocular permeation and retention compared to chitosan oligosaccharide/PLGA and trehalose/PLGA NPs. No ocular irritation in vivo was detected after applying modified/unmodified PLGA NPs to rabbit's eyes.
2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.
2-HP-β-CD/PLGA NPs are a promising nanoplatform for localized ocular drug delivery through topical administration.Exosomes or small extracellular vesicles are considered a new generation of bioinspired-nanoscale drug delivery system (DDS). Endogenous exosomes function as signalosomes since they convey signals via ligands or adhesion molecules located on the exosomal membrane, or packaged inside the exosome. Recently, exosome membrane modification, therapeutic payloads encapsulation, and modulation of in vivo disposition of exosomes have been extensively investigated, among which significant advances have been made to optimize exosome-mediated delivery to solid tumors. Exosomes, specifically tumor cell-derived exosomes, are presumed to have tumor-preferential delivery due to the homotypic features. However, quality attributes that dictate the tissue distribution, cell type-selective uptake, and intracellular payload release of the administered exosomes, as well as the spatiotemporal information regarding exosome fate in vivo, remain to be further investigated. This review summarizes recent advances in developing exosomes as drug delivery platforms with a focus on tumor targeting. The pharmacokinetic features of naive exosomes and factors influencing their intracellular fate are summarized. URMC-099 Recent strategies to improve tumor targeting of exosomes are also reviewed in the context of the biological features of tumor and tumor microenvironment (TME). Selected approaches to augment tumor tissue deposition of exosomes, as well as methods to enhance intracellular payload delivery, are summarized with emphasis on the underlying mechanisms (eg, passive or active targeting, endosomal escape, etc.). In conclusion, this review highlights recently reported tumor-targeting strategies of exosome-based drug delivery, and it's in the hope that multiple approaches might be employed in a synergistic combination in the development of exosome-based cancer therapy.
Autologous bone grafts are the gold standard for treating bone defects. However, limited bone supply and morbidity at the donor site restrict its extensive use. Therefore, developing bone graft materials as an alternative to autologous grafts has gained considerable attention. Injectable hydrogels endowed with osteogenic potential have the ability to fill irregular bone defects using minimally invasive procedures and have thus been attracting researchers' attention. However, from a clinical perspective, most fabrication methods employed for the current injectable osteogenic hydrogels are difficult and inconvenient. In the current study, we fabricated an injectable osteogenic hydrogel using a simple and convenient strategy.
Gelatin-methacryloyl (GelMA) pre-polymer was synthetized. Nano silicate (SN) and stromal cell-derived factor-1 alpha (SDF-1α) were introduced into the pre-polymer to achieve injectability, controlled release property, excellent osteogenic ability, and efficient stem cell homing.
The GelMA-SN-SDF-1α demonstrated excellent injectability via a 17-G needle at room temperature. The loaded SDF-1α exhibited a long-term controlled release pattern and efficiently stimulated MSC migration and homing. The GelMA-SN-SDF-1α hydrogel amplified cell spreading, migration, osteogenic-related biomarker expression, and matrix mineralization. The GelMA-SN-SDF-1α hydrogel filled critical-sized calvaria defects in rats and demonstrated excellent bone regeneration ability, as assessed using micro-CT scanning and histomorphometric staining.
The GelMA-SN-SDF-1α hydrogel provides a simple and convenient strategy for the fabrication of injectable osteogenic graft materials.
The GelMA-SN-SDF-1α hydrogel provides a simple and convenient strategy for the fabrication of injectable osteogenic graft materials.
Meloxicam (MX) is a potent hydrophobic non-steroidal anti-inflammatory drug used to reduce inflammation and pain. However, its oral dosage form can cause many adverse gastrointestinal effects. In the present study, a poloxamer P407 based hydrogel system containing transfersomes or flavosomes has been prepared as a potential therapeutic vehicle for the topical delivery of MX.
In this study, MX was encapsulated in conventional liposomes, transfersomes, and flavosomes. The obtained liposomal vesicles were characterized in terms of size, drug entrapment efficiency, zeta potential, and stability. These MX-loaded liposomal formulations were further incorporated into a poloxamer P407 gel and evaluated using rheological properties, a stability study and an ex vivo permeation study through human cadaver skin by both HPLC analysis and confocal laser scanning microscopy (CLSM).
The developed deformable liposomes exhibited homogeneous vesicle sizes less than 120 nm with a higher entrapment efficiency as compared to conventional liposomes. The deformable liposomal gel formulations showed improved permeability compared to a conventional liposomal gel and a liposome-free gel. The enhancement effect was also clearly visible by CLSM.
These deformable liposomal hydrogel formulations can be a promising alternative to conventional oral delivery of MX by topical administration. Notably, flavosome-loaded gel formulations displayed the highest permeability through the deeper layers of the skin and shortened lag time, indicating a potential faster on-site pain relief and anti-inflammatory effect.
These deformable liposomal hydrogel formulations can be a promising alternative to conventional oral delivery of MX by topical administration. Notably, flavosome-loaded gel formulations displayed the highest permeability through the deeper layers of the skin and shortened lag time, indicating a potential faster on-site pain relief and anti-inflammatory effect.Since the identification of the first human coronavirus in the 1960s, a total of six coronaviruses that are known to affect humans have been identified 229E, OC43, severe acute respiratory syndrome coronavirus (SARS-CoV), NL63, HKU1, and Middle East respiratory syndrome coronavirus (MERS-CoV). Presently, the human world is affected by a novel version of the coronavirus family known as SARS-CoV-2, which has an extremely high contagion rate. Although the infection fatality rate (IFR) of this rapidly spreading virus is not high (ranging from 0.00% to 1.54% across 51 different locations), the increasing number of infections and deaths has created a worldwide pandemic situation. To provide therapy to severely infected patients, instant therapeutic support is urgently needed and the repurposing of already approved drugs is presently in progress. In this regard, the development of nanoparticles as effective transporters for therapeutic drugs or as alternative medicines is highly encouraged and currently needed. The size range of the viruses is within 60-140 nm, which is slightly larger than the diameters of nanoparticles, making nanomaterials efficacious tools with antiviral properties.