The solvent evaporation technique proved successful in the creation of a nanotherapeutic system incorporating Vitamin A (VA)-modified Imatinib-loaded poly(lactic-co-glycolic acid)/Eudragit S100 (PLGA-ES100). Protecting the surface of our intended nanoparticles (NPs) with ES100 shields drug release in the acidic gastric environment and guarantees the effective release of Imatinib at a higher pH in the intestine. Additionally, the high capacity of hepatic cell lines to absorb VA makes VA-functionalized nanoparticles an ideal and efficient drug delivery system. In BALB/c mice, intraperitoneal (IP) injections of CCL4, twice weekly for six weeks, were employed to induce liver fibrosis. monoterpenoid biosynthesis Mice administered orally VA-targeted PLGA-ES100 nanoparticles, tagged with Rhodamine Red, exhibited a preferential accumulation of these nanoparticles within their livers, as shown through live animal imaging. CX-5461 supplier In parallel, administering Imatinib-loaded nanoparticles with targeted delivery significantly reduced serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and substantially decreased the expression of extracellular matrix components, such as collagen type I, collagen type III, and alpha-smooth muscle actin (-SMA). Intriguingly, the histopathological assessment of liver tissues, stained with H&E and Masson's trichrome, showed that oral administration of targeted Imatinib-loaded nanoparticles led to an improvement in hepatic structure, ultimately reducing hepatic damage. Imatinib-laden targeted nanoparticles, as observed through Sirius-red staining, contributed to a reduction in collagen levels during the treatment period. Immunohistochemistry of liver tissue exposed to targeted NP treatment exhibits a considerable decrease in -SMA protein expression. Concurrently, a precisely measured, and extremely low, dose of Imatinib, delivered via targeted nanoparticles, resulted in a notable reduction in the expression of fibrosis marker genes such as Collagen I, Collagen III, and smooth muscle alpha-actin. Our findings demonstrated that novel pH-sensitive VA-targeted PLGA-ES100 nanoparticles successfully delivered Imatinib to hepatic cells. Administering Imatinib within a PLGA-ES100/VA matrix could potentially address several hurdles inherent in traditional Imatinib treatment, such as the impact of gastrointestinal acidity, suboptimal concentration at targeted sites, and adverse effects.
From Zingiberaceae plants, Bisdemethoxycurcumin (BDMC) is isolated and showcases noteworthy anti-tumor efficacy. Still, the water-insolubility characteristic of this compound restricts its deployment in clinical practice. A microfluidic chip device, as described herein, facilitates the loading of BDMC into the lipid bilayer, ultimately forming BDMC thermosensitive liposomes (BDMC TSL). Glycyrrhizin, a naturally occurring active ingredient, was selected as the surfactant to improve the solubility of BDMC. Epigenetic change The in vitro cumulative release of BDMC TSL particles was significantly increased, owing to their small, uniform particle size distribution. We scrutinized the anti-tumor effects of BDMC TSL on human hepatocellular carcinomas by implementing a multifaceted investigative strategy including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, live/dead staining, and flow cytometry. Liposome formulation demonstrated a marked ability to inhibit cancer cell growth and migration, with an effect escalating with increasing dose. Further research on the underlying mechanisms unveiled that the combination of BDMC TSL and mild local hyperthermia considerably increased B-cell lymphoma 2-associated X protein levels and decreased B-cell lymphoma 2 protein levels, ultimately leading to cellular apoptosis. Mild local hyperthermia was applied to decompose BDMC TSLs, which were originally fabricated by microfluidic devices, thereby potentiating the anti-tumor activity of the raw insoluble materials and promoting the translation of liposomes.
The key parameter of nanoparticle size directly impacts their capacity to overcome the skin barrier, however, the full extent of the effect and underlying mechanisms associated with nanosuspensions are currently not fully understood. This study investigated the dermal delivery efficiency of andrographolide nanosuspensions (AG-NS), with particle sizes spanning 250 nm to 1000 nm, and explored how particle size affected their skin permeation. Using the ultrasonic dispersion method, gold nanoparticles with particle sizes of approximately 250 nm (AG-NS250), 450 nm (AG-NS450), and 1000 nm (AG-NS1000) were successfully fabricated and subsequently examined via transmission electron microscopy. The Franz cell method compared drug release and penetration through intact and barrier-compromised skin, while laser scanning confocal microscopy (LSCM) and histopathological examination were employed to investigate the underlying mechanisms by visualizing penetration routes and observing skin structural alterations. Our results highlighted that a decrease in particle size was associated with an increase in drug retention within the skin and its sub-layers; moreover, the drug's ability to permeate the skin showed a definite relationship to particle size, from 250 nm to 1000 nm. The in vitro drug release and ex vivo permeation through intact skin displayed a consistent linear correlation across different preparations and within each preparation, highlighting the release process as the primary determinant of drug permeation through the skin. Using LSCM, it was determined that all these nanosuspensions successfully transported the drug to the intercellular lipid space, and moreover, blocked the hair follicles in the skin, exhibiting a parallel size-related effect. A histopathological examination revealed that the formulations caused the skin's stratum corneum to loosen and swell, although no significant irritation was observed. Finally, reducing nanosuspension particle size will significantly promote the retention of topical drugs, primarily by controlling the rate at which the drug is released.
Recent years have shown a significant expansion in the utilization of variable novel drug delivery systems. In current drug delivery systems (DDS), the cell-based DDS stands out by harnessing the unique biological functions of cells to transport medication to the affected area; it is the most complex and sophisticated DDS currently in existence. The circulation time of cell-based DDS is potentially longer than that of the traditional DDS, in the body. Cellular-based drug delivery systems are expected to be the preeminent carrier for achieving multiple drug delivery functionalities. This paper investigates and details common cellular drug delivery systems like blood cells, immune cells, stem cells, tumor cells, and bacteria, featuring recent relevant research examples. This review aims to offer a framework for future research on cell vectors, driving the innovative development and clinical implementation of cell-based drug delivery systems.
The plant species known as Achyrocline satureioides, named (Lam.), holds a significant place in botanical classifications. The DC (Asteraceae), a native plant of the subtropical and temperate southeastern regions of South America, is widely recognized by the common names marcela or macela. This species exhibits a range of biological activities, including digestive, antispasmodic, anti-inflammatory, antiviral, sedative, and hepatoprotective properties, as noted in traditional medicine, among other effects. It has been observed that some activities of these species are linked to phenolic compounds—including flavonoids, phenolic acids, terpenoids present in essential oils, coumarins, and phloroglucinol derivatives—as documented for the species. The technological advancements in phytopharmaceutical product development within this species resulted in improved methods for extracting and producing various forms, such as spray-dried powders, hydrogels, ointments, granules, films, nanoemulsions, and nanocapsules. A. satureioides extracts or derivatives have been shown to possess biological activities such as antioxidant, neuroprotective, antidiabetic, antiobesity, antimicrobial, anticancer effects, along with the potential for treating obstructive sleep apnea syndrome. The species's reported scientific and technological findings, coupled with its traditional use and cultivation practices, highlight its significant potential for a variety of industrial applications.
Significant advancements have been made in the therapeutic approach for hemophilia A, but numerous clinical obstacles remain, specifically the development of inhibitory antibodies targeting factor VIII (FVIII) affecting roughly 30% of people with severe hemophilia A. Repeated long-term exposure to FVIII is typically necessary, utilizing a range of protocols, to accomplish immune tolerance induction (ITI). A novel ITI choice, gene therapy, has recently come into prominence, supplying a consistent, inherent source of FVIII. This review, in view of expanded therapeutic options, such as gene therapy, for people with hemophilia A (PwHA), examines the persistent unmet medical needs regarding FVIII inhibitors and effective immune tolerance induction (ITI) in PwHA, the immunology of FVIII tolerization, the most recent research on tolerization strategies, and the function of liver-directed gene therapy to facilitate FVIII immune tolerance.
While cardiovascular medicine has seen improvements, coronary artery disease (CAD) still stands as a major contributor to fatalities. Platelet-leukocyte aggregates (PLAs), a feature of this condition's pathophysiology, require further evaluation to determine their potential as either diagnostic/prognostic tools or as targets for therapeutic interventions.
This study investigated the characteristics of PLAs in individuals diagnosed with CAD. An important part of our research was to understand how platelet levels relate to the diagnosis of coronary artery disease. In parallel, the resting levels of platelet activation and degranulation were assessed in patients with CAD and control groups, and their correlation with PLA levels was evaluated. The investigation into the impact of antiplatelet therapies on platelet count fluctuations, basal platelet activation responses, and degranulation processes was performed on individuals with CAD.