Drug Design, Development and Therapy最新文献

Purpose: The aim was to evaluate its antinociceptive potency by comparing the effect of oliceridine and sufentanil on the half maximal effective concentration (EC₅₀) of remifentanil in suppressing the cardiovascular response to endotracheal intubation under general anesthesia.

Patients and methods: A total of 120 patients scheduled for thyroid nodulectomy were randomized into four groups: (i) control group, (ii) sufentanil group, (iii) oliceridine 0.015 mg/kg group, and (iv) oliceridine 0.03 mg/kg group. The initial dosage of remifentanil for induction of general anesthesia was 3 ng/mL. The subsequent infusion dosage of remifentanil was adjusted based on the response to endotracheal intubation in the previous patient in the group, defined as a ≥ 15% change in heart rate (HR) or mean arterial pressure (MAP) before and after intubation. Adjustments were made in increments or decrements of 0.2 ng/mL. The control group received no additional medication, whereas the sufentanil group was administered a 0.15 μg/kg intravenous (IV) bolus of sufentanil. The two oliceridine groups received IV boluses of oliceridine either 0.015 mg/kg or 0.03 mg/kg respectively. Postoperative airway complications, encompassing hoarseness, sore throat, and dysphonia, were also documented.

Results: The EC₅₀ values of remifentanil was 3.728 ng/mL (95% CI: 3.536-3.943 ng/mL), 2.824 ng/mL (95% CI: 2.620-3.015 ng/mL), 3.045 ng/mL (95% CI: 2.852-3.239 ng/mL) and 2.887 ng/mL (95% CI: 2.689-3.085 ng/mL) in the control, sufentanil, oliceridine 0.015 mg/kg group and oliceridine 0.03 mg/kg group, respectively.

Conclusion: The effect of 0.03 mg/kg oliceridine is similar to 0.15 μg/kg sufentanil in reducing the EC₅₀ of remifentanil in inhibiting the cardiovascular responses induced by trachea intubation.

Background: Cisplatin-based chemotherapy for oral squamous cell carcinoma (OSCC) is limited by intrinsic inefficacy and toxicity. Lycopene, a natural carotenoid, may enhance cisplatin's therapeutic potential.

Objective: To explore lycopene's chemo-sensitizing effects on cisplatin and its mechanisms in OSCC.

Methods: In vitro, CAL-27/SCC-9 cells were treated with lycopene and/or cisplatin; cell viability, colony formation, migration, invasion, and apoptosis were detected, and protein expression of MRP-1, PI3K/Akt/mTOR pathway components, and EMT markers was analyzed by Western blot. In vivo, a nude mouse xenograft model was used to verify the combination's effect on tumor growth.

Results: Compared with cisplatin alone, the lycopene-cisplatin combination significantly inhibited OSCC cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. Mechanistically, lycopene reversed cisplatin-induced upregulation of MRP-1 and activation of the PI3K/Akt/mTOR pathway, and restored cisplatin-suppressed E-cadherin while reducing N-cadherin and EpCAM. In vivo, the combination reduced tumor growth vs cisplatin alone without increasing toxicity.

Conclusion: This is the first report that lycopene enhances cisplatin sensitivity in OSCC by coupling inhibition of MRP-1-mediated drug efflux with suppression of PI3K/Akt/mTOR and EMT/stemness-filling the gap of lycopene's synergistic mechanism with cisplatin, offering a strategy to improve therapeutic efficacy without exacerbating toxicity.

The delivery of inhaled drugs is a critical and evolving strategy in modern medicine that offers distinct advantages over other routes of administration. Compared to traditional methods such as oral, intravenous, or transdermal delivery, inhalation provides rapid onset, high local drug concentrations, reduced systemic side-effects, and improved patient compliance. In addition to its established use for the treatment of respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), recent technological advancements have expanded its application in systemic therapies, vaccines, and biologics. Innovative devices like dry powder inhalers, soft mist inhalers, and smart inhalers, integrated with digital health technologies, enable precise dosing, adherence monitoring, and potential personalization of therapy. Emerging trends, such as inhaled nanoparticles, gene and RNA therapies, and inhaled vaccines, have redefined the landscape of inhalation drug delivery. Despite these advances, challenges remain in terms of formulation stability, device compatibility, interpatient variability, and environmental concerns related to propellants. Future research should emphasize green technologies, integration with telehealth, patient-specific inhaler matching, and broader therapeutic applications beyond pulmonary diseases. As device engineering, digital health, and biopharmaceutical research converge, inhalation therapy has become an essential component of precision and patient-centric medicine, providing new avenues for disease treatment and prevention under both local and systemic conditions.

Piper longum Linn (P. longum), a historically revered culinary spice and medicinal herb, has transitioned from its traditional roots in Ayurveda, Siddha, and Unani medicine to modern biomedical and technological applications. This review provides a comprehensive overview of its phytochemistry, therapeutic potential, and translational relevance in drug development. Rich in bioactive compounds such as piperine, piperlongumine, and piperlonguminine, P. longum exhibits significant antimicrobial, antioxidant, anti-inflammatory, cardioprotective, antidiabetic, and anticancer activities. Emerging studies also highlight its role as a bioenhancer, functional food ingredient, and sustainable source for nutraceuticals. Furthermore, advances in nanotechnology including liposomes, cubosomes, and transgelosomes, have enhanced its solubility, bioavailability, and targeted pharmacological efficacy. Industrial applications span nutraceuticals, phytopharmaceuticals, and green nanotechnology, underscoring its potential for commercialization. Clinical and preclinical studies validate its efficacy and safety within therapeutic ranges. By bridging ancient knowledge with modern innovations, this review highlights P. longum as a versatile candidate for integrative medicine and novel drug delivery strategies.

Peptide-drug conjugates (PDCs) are modular, targeted therapeutics composed of a homing peptide linked to a cytotoxic or modulating drug payload via a cleavable/non-cleavable linker. PDCs utilize peptide targeting to enhance the delivery of potent drugs to tumors, providing advantages such as superior tissue penetration, reduced immunogenicity, and simpler manufacture compared to antibody-drug conjugates (ADCs). A comparison of PDCs versus ADCs highlights that PDCs' small size (~1-3 kDa) enables deeper tumor penetration and faster clearance, whereas ADCs (~150 kDa) benefit from prolonged circulation but suffer from limited tissue diffusion. This review surveys recent advances in PDC design and application. We discuss key design elements (targeting peptides, cleavable/non-cleavable linkers, and payloads) and how these drive mechanisms of tumor delivery and intracellular drug release. Mechanistically, PDCs bind receptors or translocate across membranes, undergo endocytosis, and exploit stimuli-responsive linkers or cell-penetrating peptides to release drugs. Many PDCs can self-assemble into nanoscale structures in aqueous environments. We illustrate PDC concepts through specific instances, such as the brain-penetrant paclitaxel trevatide (ANG1005, paclitaxel-Angiopep-2), the radiotherapeutic lutetium (¹⁷⁷Lu)-DOTATATE (Lutathera), and the LyP-1-conjugated doxorubicin-loaded liposomes (LyP-1-doxorubicin conjugate) for triple-negative breast cancer. Persistent challenges include in vivo stability (premature drug release and metabolic clearance), tumor heterogeneity (variable receptor expression), and manufacturing scale-up. We also address regulatory hurdles that have limited PDC clinical success; for example, currently, only lutetium (¹⁷⁷Lu)-DOTATATE is FDA-approved (others, like melphalan flufenamide (melflufen), have faced setbacks). Finally, we outline future directions, including theranostic PDCs, AI-assisted peptide optimization, dual-stimuli linkers, and integration with nanomaterials, to further enhance targeting and efficacy. This comprehensive review integrates findings from recent literature and provides an in-depth perspective on the design, advantages, limitations, and future prospects of PDCs in cancer therapy.

Introduction: The genus Vitex L. (Verbenaceae) comprises ~250 species globally, with long-standing ethnopharmacological value. Notably, only Traditional Chinese Medicine (TCM) explicitly applies Vitex negundo for ischemic stroke (documented in classic Materia medica), distinguishing it from other regional uses (eg, menstrual disorders, malaria) and providing a unique basis for anti-stroke research.

Materials and methods: Through systematic searches of English and Chinese databases such as Web of Science, Pubmed, CNKI, and Wanfang Data. This review systematically summarizes the natural constituents of Vitex L. their anti-ischemic stroke efficacy, and underlying mechanisms, emphasizing the uniqueness of Vitex-specific components and guiding preclinical optimization and clinical translation.

Results: Over 200 constituents were identified, with flavonoids (vitexin, isovitexin, casticin), terpenoids (vitexilactone, rotundifuran), and phenols as core active components. High-evidence compounds (validated by both in vitro and in vivo experiments) such as vitexin (10-50 mg/kg) reduced rat MCAO infarct volume by 30-40% via blocking NMDA receptor-mediated Ca²⁺ overload. Mechanistically, components target neurons, glia, and vascular endothelial cells, regulating both classic pathways (Nrf2, NF-κB, PI3K/Akt) and frontier mechanisms (ferroptosis, pyroptosis, epigenetic regulation). Synergistic effects of multi-component mixtures and optimized extraction/synthesis address low-content challenges.

Conclusion: Vitex L. exhibits significant anti-ischemic stroke potential, with unique components and multi-pathway regulation as core advantages. Future research should focus on multi-center validation, synergistic mechanism exploration, and clinical trials of high-evidence components to advance translation.

Kadsura coccinea (Lem). A.C.Sm. has a long history of use in traditional Dong medicine for activating Qi, relieving pain, and dispersing blood stasis. It has garnered increasing attention for treating rheumatoid arthritis (RA), a condition associated with synovial inflammation and tissue damage. K. coccinea L. effects anti-RA by eliminating reactive oxygen species and directly or indirectly inhibiting lipid peroxidation. This review summarizes its potential therapeutic effects on RA through regulating inflammatory cytokines, reducing oxidative stress, and targeting specific cells and pathways, forecasting its future application prospects.

Bixin, a vibrant apocarotenoid derived from the seeds of Bixa orellana Linn. (commonly known as annatto), has been traditionally used as a natural colorant. However, recent advances have unveiled its diverse pharmacological and therapeutic potential, positioning it as a promising candidate in modern drug discovery and delivery systems. This review presents a comprehensive overview of bixin, encompassing its chemical structure, biosynthetic pathways, physicochemical characteristics, extraction techniques and novel nanodrug delivery systems. We critically examine its biological activities, including antioxidant, anti-inflammatory, anticancer, antimicrobial, neuroprotective, hepatoprotective, nephroprotective, and photoprotective effects, supported by mechanistic insights such as activation of the NRF2 pathway, suppression of STAT6 signaling, and modulation of oxidative stress and inflammatory mediators. Despite its wide-ranging bioactivities, the clinical application of bixin remains limited due to challenges related to its solubility, stability, and bioavailability. To address these limitations, innovative formulation strategies, including nanoparticle encapsulation, sustained-release systems, and polymer conjugates have been explored to enhance its pharmacokinetic profile and therapeutic efficacy. Majorly, field of nano-pharmaceutical technologies provides deep insights to overcome physiochemical challenges and enhance the therapeutic potential of bioactive agents. Nowadays, lipid-based nanodrug delivery approaches contribute in an efficient manner. Additionally, its integration into functional foods, cosmeceuticals, and photoprotective applications highlights its interdisciplinary relevance. This review uniquely bridges the gap between traditional knowledge and contemporary pharmaceutical science by consolidating current findings on bixin's pharmacological roles and delivery challenges. It also proposes future directions for translating bixin into a next-generation phytopharmaceutical through advanced formulation, mechanistic validation, and clinical evaluation. Collectively, the evidence positions bixin not merely as a natural colorant, but as a versatile bioactive molecule with significant promise in drug design, development, therapy, and delivery.

Moringa oleifera Lamk. a highly valued multipurpose plant, has gained increasing attention owing to its diverse pharmacological properties, including immunomodulatory, antioxidant, and antidiabetic effects. This narrative review evaluates published human studies and case reports from 2015 to 2025 to assess the efficacy and safety of M. oleifera and the underlying mechanisms of its pharmacological effects. A narrative review was chosen over a systematic review because it is flexible, broad-focused, and interpretive, and thus is suitable for mapping emerging fields. A total of 22 clinical trials and nine case reports met the inclusion criteria. This review focuses on five major clinical themes: immunological and nutritional effects, metabolic and endocrine disorders, inflammatory and oxidative stress-related diseases, maternal and child health outcomes, and other clinical applications. Evidence from human studies indicates consistent improvements in immune function, glycemic control, and antioxidant status, particularly among individuals with HIV infection, prediabetes, and malnutrition. Maternal supplementation also enhances the vitamin A content and nutritional outcomes in infants. Mechanistically, these effects are linked to the immune system (modulation of cytokine activity, activation of AMP-activated protein kinase, and antioxidant activity) and to metabolic pathways (inhibition of α-glucosidase and dipeptidyl peptidase IV). Although it is generally well tolerated, rare hypersensitivity and thrombotic events have been reported. Collectively, M. oleifera shows promising potential as a safe and accessible functional food and a nutraceutical or adjunct therapeutic candidate for immune and metabolic disorders, thus warranting further standardized, large-scale randomized controlled trials to confirm its long-term efficacy and safety.

Background/objectives: Hip osteoarthritis (OA) induces chronic pain and disability in aging populations. Opioids are increasingly prescribed for refractory hip OA pain; however, comparative safety data are limited. This study aimed to compare the psychiatric, cardiovascular and skeletal outcomes between codeine and oxycodone in patients with hip OA.

Methods: A population-based retrospective cohort using Korean Health Insurance Review and Assessment Service (HIRA) claims data was performed in hip OA (M16) patients who initiated codeine or oxycodone. Propensity score matching (PSM) was applied with sensitivity analyses performed using inverse probability of treatment weighting (IPTW). Outcomes included composite psychiatric outcomes (depression, anxiety, bipolar disorder, sleep disorders, and schizophrenia), major adverse cardiovascular outcomes (MACE; myocardial infarction, stroke, cardiovascular death/arrest, heart failure hospitalization), and fractures. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models.

Results: A total of 16,162 patients were included in the cohort after 1:1 PSM. Codeine was associated with a higher risk of psychiatric disorders (HR 1.11, 95% CI 1.04-1.19), particularly anxiety (HR 1.14, 95% CI 1.03-1.26) and sleep disorders (HR 1.15, 95% CI 1.02-1.30). Risks of MACE (HR 1.02, 95% CI 0.92-1.14) and death (HR 1.03, 95% CI 0.92-1.14) were comparable between groups. Codeine was associated with a higher risk of non-femoral fractures (HR 1.10, 95% CI 1.04-1.16). Subgroup analyses revealed differentiated risks across age, sex, comorbidities, and concomitant medications.

Conclusion: Codeine use in patients with hip osteoarthritis was associated with a higher risk of psychiatric disorders and distinct fracture patterns. The observed risks varied according to patient characteristics, comorbidities, and concomitant medications, emphasizing the need for individualized opioid prescribing strategies that incorporate psychiatric monitoring, fracture risk assessment, and patient-specific factors. Further controlled studies integrating clinical, lifestyle, and genetic data are warranted to confirm these findings and refine personalized opioid therapy in hip osteoarthritis.