Journal of Pharmacy and Pharmacology最新文献

Objectives: The primary objective of this review is to summarize research cases and recent advances in ultrasound technology for overcoming the blood-brain barrier (BBB) and facilitating drug delivery to the brain, thereby providing insights to promote research on enhancing drug permeation across the BBB.

Key findings: This review summarizes recent advances in focused ultrasound combined with microbubbles to enhance BBB permeability for brain-targeted drug delivery. It covers the mechanisms by which ultrasound and microbubbles open the BBB, the factors influencing this process, and their applications in brain diseases. Finally, existing challenges in the field are highlighted, and the prospects for clinical translation are discussed.

Summary: Ultrasound combined with microbubble technology can safely, non-invasively, and reversibly open the BBB and deliver drugs, offering novel strategies and methods for the treatment of brain diseases.

Objectives: Traditional Chinese Medicine (TCM) has garnered significant interest for its role in modulating gut microbiota to inhibit tumor progression. This review aims to systematically elucidate the mechanistic basis for TCM-mediated antitumor activity via gut microbiota modulation. Based on the microbiota-immune axis theory, it also intends to investigate the optimizing effects of TCM on traditional tumor treatment modalities. By establishing a theoretical foundation for the role of TCM in microbiota-mediated immunotherapy, this review also provides evidence supporting its multi-target and cross-organ antitumor properties.

Methods: All the information was collected through library searches and scientific databases.

Key findings: Gut microbiota dysbiosis promotes tumors not only in the digestive system but also beyond it, via gut-organ-axis signaling and metabolic mechanisms. TCM modulates host immunity both through gut microbiota remodeling and microbial metabolite-mediated activation of immune cells. Similarly, via the gut microbiota, TCM can reduce toxicity and enhance the efficacy of conventional cancer therapies. During TCM treatment, as the gut microbiota undergoes dynamic succession, its regulatory effect on the host immune system exhibits corresponding time-dependent changes.

Conclusions: Research on gut microbiota-mediated TCM immunotherapy demonstrates the theoretical basis for TCM's trans-organ antitumor effects.

Objectives: To investigate the Bazhen decoction (BZD) mechanism in the treatment of liver cancer (LC).

Methods: Integrative approach combining network pharmacology, HPLC, molecular docking, public cancer databases, and MTT colorimetric assay to elucidate the pharmacological mechanisms of BZD against LC.

Key findings: We identified 647 common targets between BZD and LC, with PPI analysis revealing SRC, PIK3CA, AKT1, HSP90AA1, and STAT3 as core targets. KEGG pathway analysis further highlighted PI3K-AKT, MAPK, HIF-1, and Rap1 signaling pathways as critical mechanisms mediating BZD's therapeutic effects. Notably, validation using cancer databases showed that many core targets exhibit differential messenger RNA (mRNA) and protein expression between LC and normal tissues, with their expression levels significantly associated with the overall survival of LC patients. Molecular docking analysis revealed strong binding affinities between the majority of core compounds and their corresponding core targets. HPLC analysis was performed using neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, ferulic acid, and senkyunolide I as reference standards. MTT assays confirmed that BZD significantly inhibited the proliferation of HepG2 and Huh7 cells in a time- and dose-dependent manner.

Conclusions: BZD exerts anti-LC effects through multi-target regulation, particularly involving AKT1, PIK3CA, SRC, and HSP90AA1, as well as suppression of the PI3K-AKT signaling pathway. These findings provide a mechanistic basis for its potential clinical application in LC therapy and warrant further in vivo investigation.

Background: Ventilator-associated pneumonia (VAP) is a significant cause of patient morbidity and mortality worldwide. This study describes a strategy to develop antibacterial hydrogel-based coating for endotracheal tubes, composed of 2-hydroxyethyl methacrylate and methacrylic acid, capable of simultaneously delivering a combination of antibacterial agents to mitigate VAP.

Methods: Copolymer hydrogels were loaded with gentamicin, levofloxacin, and benzalkonium chloride (BAK), and their drug release profiles, antibacterial activity, and duration were determined.

Key findings: More than 95% and 99.99% reduction of bacterial adherence was observed for all the antibiotic-containing hydrogels after 4 and 24 h, respectively. Hydrogels loaded with BAK provided protection against Staphylococcus aureus for more than 30 days and hydrogels loaded with levofloxacin exhibited more than 10 days of persistence against Pseudomonas aeruginosa. Dual loading of levofloxacin and BAK showed additive effects against bacteria and provided delayed release of both agents.

Conclusions: The use of combined antibiotic-loaded hydrogel coatings provides a promising approach to combating the development of VAP.

Objectives: Carvedilol (CDL) is an oral beta-adrenergic blocker known for enhancing arterial blood flow and reducing hyperglycemia due to its antioxidant properties. However, CDL's short half-life leads to its low efficacy and poor bioavailability. This study aimed to develop a nasal spray of CDL-loaded transbilosomes (CTB) to improve CDL's sustainability, bioavailability, targeting, and effectiveness in controlling atherosclerosis in rats.

Methods: Various CTB formulations were created using a Box-Behnken design to examine the effects of phospholipid, Span 60, and sodium deoxycholate (SDC) levels. In vivo evaluation of this optimal CTB formulation in a rat model of experimental diabetic high-fat diet-induced atherosclerosis was conducted.

Key findings: The formulation containing 274.33 mg of phospholipid, 26.67 mg of Span 60, and 22.45 mg of SDC was identified as the optimal formulation. When compared with free CDL, the optimal CTB formulation enhanced sustainability, bioavailability, and targeting of CDL by 72.43%, 7.43-fold, and 7.55-fold, respectively. The nasal CTB group showed significant reductions in blood levels of glucose, triglycerides, cholesterol, and LDL, while increasing HDL and survival rates compared with the disease group. A histopathological study confirmed the efficacy of the nasal CTB spray.

Conclusion: The nasal CTB spray could be a potential therapy in controlling atherosclerosis in rats.

Objectives: To date, ~70 long-acting injectable (LAI) formulations have been developed. More than half of these formulations consist of oily solutions and suspensions containing poorly water-soluble drugs. However, numerous drugs do not fall into the category of poor solubility, such as hydrophilic small molecules, nucleic acids, peptides, and proteins. These drugs are typically formulated using biodegradable poly(lactide-co-glycolide) polymers. An important question to consider is whether there are guiding principles for selecting appropriate drugs for LAI formulations. The historical advancements and challenges associated with LAI formulations were examined to identify indicators that may predict effective drug candidates for this type of delivery system.

Key findings: Several properties of drugs, including water solubility, lipophilicity, tissue permeability, half-life (t1/2), and effective dosage, were analysed in relation to the development of LAIs. This study investigated several parameters to forecast formulation success, with a focus on achieving an optimal balance between the drug's partition coefficient (logP), which reflects both water solubility and cellular permeability, and the effective dose.

Summary: The current overview of recent innovations and formulation considerations indicates that a systematic approach, integrating two key parameters, logP and the effective dose of a drug, may be employed for the preliminary screening of drugs that have the potential to be formulated into LAIs with a higher probability of success in clinical applications.

Objectives: This review examines the signalling pathways involved in head and neck cancer cell survival and apoptosis.

Methods: Articles were sourced from Scopus using the following keywords: oral cavity cancer, head and neck squamous cell carcinoma, signalling pathways, target therapy. No publication date limits were set, and the language of publication was restricted to English.

Key findings: Head and neck cancers are the sixth most common cancer worldwide (head and neck squamous cell carcinoma [HNSCC]). The most common subtype is squamous cell carcinoma (SCC), with oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC, respectively) being significant subcategories. Multiple signalling pathways play a critical role in oncogenesis and the development of various head and neck malignancies. Theoretically, targeting inhibitors for these pathways could potentially halt tumour growth and restore affected cells. This review highlights key oncogenic cascades, including epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT/mTOR, mitogen-activated protein kinase/extracellular signal-regulated kinase, Wnt/β-catenin, NOTCH, the p53 gene, and vascular endothelial growth factor, which contribute to tumour progression, invasion, and therapeutic resistance. A comprehensive understanding of these molecular mechanisms is essential to inform targeted therapies and develop personalized treatment strategies for HNSCC.

Conclusions: Researchers have studied several signalling pathways in HNSCC due to their known ability to influence apoptosis, survival, angiogenesis, and other biological processes.

Objectives: Neuroblastoma (NB), the most common extracranial tumor in childhood, has a poor prognosis, especially in cases with MYC gene amplification. Cisplatin (CDDP) is widely used in treatment, but its effectiveness is limited due to chemotherapy resistance. Autophagy plays a dual role in cancer progression, either promoting survival or contributing to cell death.

Methods: This study explores the anticancer effects of K41-A, a polycyclic polyether molecule, alone and in combination with CDDP in SH-SY5Y and KELLY NB cell lines, the HE-IOC1 noncancerous cochlear cell line, and the NB xenograft model.

Key findings: For the first time, we demonstrate that K41-A, either alone or combined with CDDP, significantly inhibits cell proliferation selectively in NB cells, sparing noncancerous cells. This study confirmed that K41-A alone and in combination with CDDP induced changes in both apoptotic and autophagic cell death components in NB, resulting in antiproliferative activity in vitro and in vivo. In addition, the combination with CDDP enhanced the therapeutic efficacy of K41-A.

Conclusions: These results highlight the potential of K41-A as a candidate drug for the treatment of NB.

Objectives: Develop a biorelevant in vitro methodology to screen adsorbents for their safety and for their efficacy to remove unabsorbed drugs from the colonic lumen using activated charcoal (AC) as a model adsorbent; Evaluate AC's usefulness in preventing drug-induced intestinal dysbiosis based on in vitro data.

Methods: Published clinical data with AC and moxifloxacin were used to evaluate biorelevance of the in vitro methodology. In vitro data with four drugs were used to evaluate the usefulness of AC in preventing drug-induced intestinal dysbiosis.

Key findings: In line with human data, in vitro data indicated that AC has no impact on osmolality and bacterial enzyme activity, and that complete removal of moxifloxacin accumulating in the colon after daily dosing requires the dispersion of >7 g Filtercarb Pharma-A to the colonic lumen. In vitro data with rosuvastatin, azithromycin, and metformin indicated that complete removal after daily dosing requires the dispersion of >3 g, ≈25 g, and >45 g Filtercarb Pharma-A, respectively, to the colonic lumen.

Conclusions: An in vitro methodology to screen adsorbents for their safety and for their efficacy in removing unabsorbed drugs from the colonic lumen was developed. The effectiveness of AC may be limited by the size and the performance variability of the colon-targeting product.

Pediatric drug development faces significant challenges due to age-specific physiological differences, with limited approved formulations often resulting in off-label or extemporaneous uses. Oral administration remains the most common route in children, with ideal formulations requiring dosing flexibility and palatability. Cyclodextrins (CDs) have emerged as effective excipients for pediatric applications due to their ability to enhance aqueous solubility, improve chemical stability, and mask unpleasant tastes. Despite their extensive use in adult formulations, their application in pediatric formulations remains limited. Pharmacokinetic studies in juvenile animals reveal age-dependent renal clearance of CDs, with neonates demonstrating delayed elimination. Clinical findings indicate that hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin are generally well tolerated in pediatric populations; however, neonatal use requires caution due to potential accumulation related to immature renal function. Despite limited regulatory approval, CD-based systems have effectively improved pediatric formulations. Advances in pediatric-friendly dosage forms, such as orodisperable tablets, mucoadhesive films, and 3D-printed mini-tablets, have further highlighted the versatility of CDs. Nonetheless, comprehensive safety data and defined regulatory guidelines are essential for broader clinical application. This review outlines the role of CD complexation in pediatric drug delivery, summarizes the relevant pharmacokinetic and toxicity findings in children, and presents examples of CD-based pediatric formulations.