Current drug metabolism最新文献

Objective: Tacrolimus, a calcineurin inhibitor (CNI), is the first-line treatment for chronic myeloid leukemia (CML) and advanced gastrointestinal stromal tumors (GIST). Imatinib and tacrolimus are both substrates of the hepatic enzymes CYP3A4/5 and efflux transporter P-gp, so drug-drug interactions may occur during their co-administration treatment. Therefore, this study aimed to evaluate the pharmacokinetic interaction between imatinib and tacrolimus in rats.

Methods: Rats were divided into groups I (30 mg/kg imatinib administered for 14 days), II (1.89 mg/kg tacrolimus and 30 mg/kg imatinib administered for 14 days), III (30mg/kg imatinib and 0.63mg/kg tacrolimus administered for 14 days), IV (1.89mg/kg tacrolimus for 14 days), and V (10mg/kg imatinib and 1.89mg/kg tacrolimus for 14 days). Blood samples were determined for whole blood of tacrolimus, plasma of imatinib, and Ndesmethyl imatinib concentrations using ultra-performance liquid chromatography-mass spectrometry.

Results: After 1 day of a single dose, tacrolimus had no significant effect on the pharmacokinetics of imatinib and N-desmethyl imatinib; imatinib significantly increased the AUC and C_max of tacrolimus (P < 0.05). After 14 days of multiple doses, tacrolimus significantly reduced the AUC and C_max of imatinib and N-desmethyl imatinib (P < 0.05). Further, imatinib significantly increased AUC_0-24 and AUC_0-∞ of tacrolimus (P < 0.05).

Conclusion: Imatinib increased tacrolimus blood concentrations after single and multiple administrations. Tacrolimus did not significantly affect the pharmacokinetics of imatinib after a single dose; however, tacrolimus might impact the absorption and metabolism of imatinib after multiple doses. The results showed that when imatinib and tacrolimus were co-administered, attention should be paid to the presence of drug-drug interactions.

Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by symptoms of hyperactivity, inattention, and impulsivity, significantly impacting individuals' daily functioning and quality of life. This manuscript explores the intricate relationship between the gut microbiome and ADHD, emphasizing the role of the gut-brain axis, a bidirectional communication pathway linking the central nervous system (CNS) and the gastrointestinal tract (GIT). The composition of gut microbiota influences several physiological processes, including immune function, metabolism, and the production of neuroactive metabolites, which are critical for cognitive functions such as memory and decision-making. The review discusses alternative therapeutic options, including dietary modifications, synbiotics, and specific diets like the ketogenic diet, which may offer promising outcomes in managing ADHD symptoms. Further research is necessary to establish the efficacy and mechanisms of action of synbiotics and dietary interventions, despite preliminary studies suggesting their potential benefits. This review article aims to provide a comprehensive overview of the current understanding of the gut microbiome's impact on ADHD, highlighting the need for continued investigation into innovative treatment strategies that leverage the gut-brain connection.

The brain is highly protected by physiological barriers, in which the blood-brain barrier restricts the entry of most drugs. Intranasal drug delivery is a non-invasive way of drug delivery, which can cross the blood-brain barrier and achieve direct and efficient targeted delivery to the brain. Therefore, it has great potential in application to the treatment of brain diseases. Temperature-sensitive hydrogels undergo a solutiongel transition with temperature change, and the gel form has good mucosal adsorption properties in the nasal cavity, which is commonly used for targeted delivery of drugs for brain diseases. In this article, by introducing the transport mechanism of brain targeting after nasal administration, combined with the prescription design and basic performance study of temperature-sensitive nasal hydrogel, we summarized the research on the role that temperature-sensitive hydrogel plays brain targeting after via nasal administration, aiming to provide a reference for the development of therapeutic drugs for cerebral diseases and their clinical application. A graphical summary.

A majority of the global population suffers from eye diseases, but few effective treatment options are available with ophthalmic drug therapies. The reasons that have been identified are (1) lack of awareness about the options for treatments, drugs, polymeric science, or physiological barriers, (2) limitations in bringing drug therapies to the posterior segment of the eye due to physiological or anatomical limitations, and (3) regulatory and production difficulties of ocular drug products. Innovative ocular medication delivery and therapies are covered in this study, including hydrogels, nano micelles, implants, nanoparticles, microparticles, liposomes, in situ gels, and microneedles. Moreover, due to their potential to capture both hydrophilic and lipophilic medications, increase ocular permeability, prolong the period of residence, enhance drug stability, and increase bioavailability, this review includes nanotechnology-based carriers. The research encompassed various eye disorders, obstacles to ocular delivery, multiple ocular administration routes, a range of nanostructured platforms, characterization approaches, methods to improve ocular delivery, and emerging technologies. This review aims to provide information on the anatomy of the eye, various ocular conditions, and obstacles to ocular delivery. The benefits and drawbacks of various ocular dose forms or delivery techniques are also evaluated. Finally, it describes methods for increasing ocular bioavailability.

Background: The rapid surge in bacterial resistance to classical antibiotics and antimicrobial agents has driven researchers to identify new classes of antimicrobial agents. At the nanoscale, nanotechnological progress has strongly underscored the application of silver and copper since they present high antimicrobial activities toward gram-positive and gram-negative bacteria. Nanostructures containing these two elements-all the more so for hybrid nanocomposites-have been scantily the subject of investigated. The present work aims to develop and study a silver/copper oxide/clay hybrid nanocomposite.

Methods: Nanocomposites of silver, copper oxide, and their hybrid with clay were synthesized via chemical precipitation under controlled pH (9-11) and temperature (60-90°C) conditions. The antibacterial activity was assessed using standard 0.5 McFarland-adjusted bacterial inocula. Characterization was performed using FTIR, XRD, FESEM, and TEM techniques. MIC and MBC were determined through serial dilution, and data were analyzed using one-way ANOVA and Tukey's test (SPSS v26).

Results: The results indicated that the fabricated nanocomposite was impure, with nanosilver particles measuring 30-40 nm and copper oxide particles measuring 200-250 nm. The morphological properties of synthesized Ag/Cu₂O/clay nanocomposites were evaluated using X-ray diffractometer analysis. The minimum inhibitory concentration (MIC) of the hybrid nanocomposite against Staphylococcus aureus and Bacillus subtilis was 1024 μg/ml, and for Escherichia coli and Pseudomonas aeruginosa 2048 μg/ml. The minimum bactericidal concentration (MBC) against Staphylococcus aureus and Bacillus subtilis was 4096 μg/ml, and for Escherichia coli 4096 μg/ml, and Pseudomonas aeruginosa 8192 μg/ml.

Discussion: Silver/copper oxide/clay hybrid nanocomposite exhibited more intensive antibacterial activities towards gram-positive bacteria in the absence of single-component nanocomposites, validating the synergistic effect of silver and copper in aid of clay. Its small efficacy on gram-negative strains also points at the necessity for additional optimization as well as extension. Such outcomes indicate the potential of the hybrid nanocomposite as an aspiring candidate for eventual antimicrobial applications.

Conclusion: These results showed that the antimicrobial property of silver/copper/clay hybrid nanocomposite was better than copper/silver and clay nanocomposite against gram-positive bacteria, while showing a similar effect against gram-negative bacteria.

Moonlighting proteins, defined by their ability to perform distinct, independent functions beyond their primary roles, have garnered attention in metabolic regulation and drug discovery. This review highlights the emerging significance of these proteins in diverse physiological and pathological processes. With examples like glycolytic enzymes and Krebs cycle components, we explore their involvement in transcriptional regulation, immune responses, and stress modulation. Their unique ability to mediate host-pathogen interactions and disease progression underscores their potential as therapeutic targets. Advanced technologies, such as proteomics and bioinformatics, have revolutionized the identification and characterization of these proteins, unraveling their structural and functional complexities. This synthesis aims to bridge gaps in understanding protein multifunctionality and advocates its implications in drug development. By targeting specific functions of moonlighting proteins while preserving their essential roles, new strategies in pharmacology and personalized medicine are envisioned. The review also proposes a roadmap for leveraging these proteins' multifunctionality to address current challenges in therapeutic interventions.

Background: Carboplatin (CP) is a widely used chemotherapeutic agent with poor oral bioavailability and potential systemic toxicity when administered intravenously. There is a growing interest in developing sustained-release oral formulations to improve therapeutic efficacy and patient compliance.

Objective: The present study aimed to develop and evaluate an oral, enteric-coated, PEGylated multi-walled carbon nanotube (MWCNT) formulation (F2) of carboplatin and assess its pharmacokinetic and histopathological profile in comparison with the marketed intravenous product, Kemocarb®.

Methods: A sensitive and robust HPLC method was developed for the quantification of CP in rabbit plasma. Stability studies were performed at 4 °C for 4 hours and -80°C for 4 weeks. Histopathological evaluation was conducted on major organs of mice to assess toxicity. CP and caffeine were extracted with minimal matrix interference. Pharmacokinetic studies were performed following oral administration of the F2 formulation and compared with Kemocarb®.

Results: The developed HPLC method demonstrated good sensitivity, accuracy, and robustness. CP was stable under both short-term and long-term storage conditions. Histological analysis revealed no significant pathological damage in mice organs. The F2 formulation exhibited sustained drug release for up to 24 hours. The Tmax, Cmax, and MRT of CP for F2 were different compared to Kemocarb®, with a relative bioavailability of 1.182 ± 0.24. The Cmax and MRT of F2 were 12.327 ± 0.03* and 3.5805 ± 0.26 h, respectively.

Conclusion: The developed F2 formulation of carboplatin demonstrates sustained release and improved relative bioavailability following oral administration. It may offer a promising alternative to commercial intravenous CP injections (Kemocarb®), potentially supporting metronomic chemotherapy strategies with improved patient compliance and reduced systemic toxicity.

Background: Numerous chronic illnesses, including diabetes, cancer, cardiovascular disease, and neurological disorders, are mostly caused by oxidative stress, which is defined as an imbalance between the body's antioxidant defenses and the generation of reactive oxygen species (ROS). The success of traditional treatments for oxidative stress has been limited because antioxidant medications are not well-absorbed, are quickly broken down, and do not target specific areas of the body.

Methods: Drug delivery methods based on nanotechnology offer a viable solution to these issues by providing therapeutic molecules with improved release characteristics, enhanced bioavailability, and targeted capabilities. Recent developments in nanotechnology have enabled the creation of multipurpose carriers that can simultaneously transmit genes for endogenous antioxidant enzymes and antioxidants.

Results: This integration promotes a long-term healing response and addresses the immediate oxidative stress. Likewise, functionalizing nanocarriers with particular ligands improves localization to oxidative stress locations, including inflammatory tissues or tumor microenvironments, boosting therapeutic efficacy. The potential of nanotherapeutics in reducing oxidative stress-driven diseases is examined in this article.

Discussion: Nanotechnology-based drug delivery approaches offer a novel avenue for the treatment of several oxidative stress-induced diseases. These delivery systems are highly target-specific and have a longer duration of action. Still, more research is needed to address issues, such as safety margins, largescale production, and approval of medicine use.

Conclusion: We address several nanocarrier platforms, such as liposomes, polymeric nanoparticles, dendrimers, and metallic nanoparticles that have proven more effective in delivering therapeutic drugs and antioxidants to specific sites of oxidative damage. Furthermore, nanotherapeutics may enhance their therapeutic potential by protecting these bioactive substances from premature degradation and clearance.

Traditional treatment methods for the management of diabetes, such as oral hypoglycemic medications and insulin injections, include drawbacks like systemic adverse effects, inconsistent medication levels, and low compliance. To avoid difficulties, glycemic levels in diabetic patients, a long-term metabolic condition, must be precisely and consistently controlled. Smart therapeutic systems allow for precise, on-demand medication release in response to local physiological or environmental cues, such as glucose levels, pH, temperature, or enzyme activity. They provide a possible substitute for conventional diabetic therapies. As these systems only administer medications when and where needed, they reduce side effects while simultaneously increasing therapeutic efficacy and patient compliance. These systems are designed to respond to signals from external sources (such as light, ultrasound, or magnetic fields) or stimuli like temperature, pH, glucose levels, and enzymes. As they use glucose-sensitive substances like phenylboronic acid, glucose oxidase, or polymers to precisely release insulin in hyperglycemic circumstances, glucose-responsive delivery methods are essential for diabetes. This review discusses a stimuli-responsive drug delivery system designed for diabetes treatment, with a focus on the developments in biomaterials, nanotechnology, and engineering that improve its effectiveness and biocompatibility. Along with the possibility of combining a stimuli-responsive drug delivery system with wearable technology for continuous glucose monitoring and intelligent insulin delivery, issues, such as manufacturing complexity, stability, and patient safety, are also addressed. The stimuli-responsive drug delivery system has the potential to revolutionize diabetes management by bridging the gap between physiological needs and therapeutic delivery, providing better glucose control, fewer side effects, and an enhanced standard of living for patients.