Advanced pharmaceutical bulletin最新文献

In the pharmaceutical industry, artificial intelligence (AI) is revolutionizing individualized therapy, research, and drug development. AI includes machine learning (ML) and deep learning (DL), that are used to read enormous amounts of data, spot mysterious patterns, and find possible medication candidates more quickly. AI is also improving clinical trials through better patient recruitment, real-time data monitoring, and trial outcome prediction. It also customizes care according on a person's genetic composition, lifestyle, and environmental factors is also supporting personalized medicine, a novel approach to healthcare. In, pharmaceutical industries it is used to simplify medicine production procedures, enhancing quality control, and streamlining supply chain management that saves the valuable time as well as billions of dollars. This comprehensive review discusses the different impacts of AI-enabled technologies on each stage of the pharmaceutical life cycle. It demonstrates that ML, data analytics and predictive modelling can accelerate drug discovery, improve manufacturing processes, streamline quality processes, enhance formulation approaches, and transform post-marketing surveillance, drug repurposing, precision medicine, and nanobots.

The advent of advanced gene delivery platforms has transformed the precision targeting of therapeutic nucleic acids, such as miRNA, siRNA, and pDNA, for the treatment of genetic and acquired diseases, including cystic fibrosis, malignancies, sickle cell anaemia, and β-thalassemia. Although viral vectors have traditionally dominated this field, non-viral systems, particularly genosomes (cationic lipid-based nanocarriers or lipoplexes), have emerged as promising alternatives due to their enhanced biosafety, lower immunogenic potential, and manufacturability. These nanostructured systems facilitate efficient nucleic acid condensation, protect against enzymatic degradation, and enhance cellular uptake and endosomal escape. Further refinements, including PEGylation, incorporation of helper lipids, and stimuli-responsive formulations, have significantly improved transfection efficiency and tissue-specific delivery. Notable clinical advancements, such as RNA-lipoplexes in cancer immunotherapy and multifunctional envelope-type nanodevices (MEND), highlight their therapeutic potential. This review provides a critical analysis of genosome design strategies, formulation techniques, intracellular trafficking mechanisms, clinical applications, patented innovations, and future prospects to advance genosome-mediated gene therapy.

Lymphedema, traditionally viewed as a mechanical consequence of lymphatic obstruction, is increasingly recognized as a complex disorder rooted in metabolic dysfunction, particularly insulin resistance and chronic hyperinsulinemia. This paradigm-shifting hypothesis redefines lymphedema as a vascular complication driven by systemic metabolic stress, where prolonged hyperinsulinemia impairs lymphatic endothelial cell (LEC) function, triggering inflammation, oxidative stress, and structural damage. Insulin resistance disrupts the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, critical for lymphangiogenesis and endothelial integrity, leading to compromised lymphatic drainage. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), exacerbate this dysfunction by activating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promoting reactive oxygen species (ROS) production, while advanced glycation end products (AGEs) engaging RAGE amplify fibrosis and endothelial apoptosis. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as liraglutide and semaglutide, offer a revolutionary therapeutic approach by addressing both metabolic and vascular components of lymphedema. By enhancing PI3K/AKT signaling, GLP-1RAs restore insulin sensitivity, mitigate hyperinsulinemia, and suppress inflammatory pathways (NF-κB, TLR4). Their activation of VEGF-C/VEGFR-3 and endothelial nitric oxide synthase (eNOS)/NO pathways promotes lymphangiogenesis and reduces ROS-induced damage, enhancing lymphatic vessel repair. Clinical evidence, including a 2024 case report, demonstrates significant reductions in limb volume (from 10.3% to 3.4%) and restored lymphatic function in breast cancer-related lymphedema following GLP-1RA therapy. Localized administration optimizes therapeutic outcomes by targeting LECs, minimizing systemic side effects. This narrative review synthesizes lymphedema's metabolic pathophysiology, proposes localized semaglutide as a novel therapy, and suggests experimental protocols to advance lymphedema management.

Purpose: Effective inhaled drug delivery is essential for managing bronchial asthma and chronic obstructive pulmonary disease (COPD). This study compared the aerosolization efficiency of two different dry powder inhalers (DPIs), the Aerolizer and Revolizer, using a fixed formulation of formoterol fumarate.

Methods: Aerodynamic particle size distribution was measured using a next-generation impactor (NGI), and delivered dose uniformity was assessed with a dosage unit sampling apparatus (DUSA), both at a fixed flow rate of 60 L/min. Drug content was quantified using a validated high-performance liquid chromatography (HPLC) method, and performance metrics were analyzed using CITDAS software. Data were averaged (mean±SD) and compared by statistical tests (e.g., ANOVA or t-tests), with P<0.05 indicating significance.

Results: The Aerolizer achieved a fine particle dose (FPD) of 4.71 µg, which was 2.39 times higher than that of the Revolizer (1.97 µg). It also delivered approximately 20% greater overall dose and showed more consistent deposition in the NGI stages. While both devices demonstrated similar fine particle fractions (FPFS), the difference in FPD was primarily due to the higher emitted dose from the Aerolizer. The use of a fixed flow rate allowed direct comparison of device performance.

Conclusion: These findings highlight the significant influence of device design on DPI performance, even when the formulation remains constant. The Aerolizer, a low-resistance inhaler, showed superior delivery efficiency than the Revolizer under standardized conditions. Future studies should include pressure-drop-adjusted or patient-simulated testing to better reflect clinical inhalation profiles and further explore how device mechanics influence drug delivery.

Purpose: This systematic review aims to critically evaluate the safety and efficacy of PRP therapy in managing interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods: Two researchers independently searched related Databases and collected all studies from inception to December 5, 2023. Outcome indicators of symptom relief were pain scores self-assessment using the VAS system, IC symptoms using the O'Leary-Sant score (OSS), urinary frequency, nocturia, post-void residual (PVR), voided volume, and functional bladder capacity.

Results: Among 372 retrieved articles, 13 studies, including 426 patients, were included. The pain of patients decreased significantly after treatment with platelet-rich plasma (PRP) compared to the baseline values (MD: -1.93, 95% CI: -2.28, -1.58). All subgroup analyses revealed a decrease in VAS scores after PRP injection. IC symptoms using OSS, and ICSI decreased significantly after treatment.

Conclusion: PRP therapy as a new and successful course of treatment may be a novel therapeutic approach in IC/BPS cases. More study with the control arm is required to enhance treatment regimens for this difficult condition and to better understand the mechanisms of action of PRP in IC/BPS.

Melasma is a prevalent pigmentary disorder characterized by irregular brown patches on sun-exposed face and neck regions, driven by increased vascular proliferation and dysregulated melanogenesis. Although benign, untreated melasma significantly impacts quality of life from emotional stress and cosmetic impairment especially for Asian women. Melasma complex and diverse aetiology involves melanocyte hyperactivity triggered by UVR exposure, genetics, hormones and aging. The effectiveness of current topical and physical therapies such as depigmenting agents, peels, photoablation and dermabrasion etc. have varying efficacy but limited by high recurrence rates. Tranexamic acid (TA) is a lysine-derived antifibrinolytic drug which has demonstrated high potential in reduction of melanogenic factors, inhibiting melanogenesis. Lipidic vesicular delivery systems including liposomes, ethosomes, niosomes, transferosomes and phytosomes showed extensive capability in the delivery of TA into deeper epidermal layers with improved stability and penetration efficacy. Multiple studies have shown that lipidic vesicular formulations of TA offer improved safety and efficacy compared to conventional delivery methods. However, further research and clinical trials will be necessary to verify the long-term safety and feasibility and to set up standardized protocols for this novel delivery system. Therefore, this review aims to scrutinize the potential of lipidic vesicles as a cutting-edge novel approach for the enhancement of TA's efficacy in melasma hyperpigmentation treatment, as well as offering possibilities for future research and clinical applications in dermatology.

Purpose: The close relationship of the toll-like receptor (TLR) signaling pathway has been indicated with different bioactivates of tumor cells. Here, the impact of TLR4 signaling pathway stimulation/inhibition was assessed on angiogenesis and exosome (Exo) biogenesis in MDA-MB-231 cells.

Methods: Cells were incubated with lipopolysaccharide (LPS) and simvastatin (SIM) for 48 hours. Cell survival and TLR4 signaling pathway genes were measured using MTT and real-time PCR analysis. The physicochemical properties of Exos were studied using DLS, SEM, and western blotting. The migration capacity and angiogenesis-related genes were assessed using the Transwell insert assay and real-time PCR analysis.

Results: Data indicated that SIM and LPS can reduce the survival rate in a dose-dependent manner compared to the control cells (P<0.05). The expression of TLR4, NF-κB, IL-1β, MYD88, and TRIF was increased in LPS-treated cells compared to the control group (P<0.05), while these genes were down-regulated or remained unchanged in the SIM group. SEM analysis indicated the reduction of Exo diameter in the LPS groups (P<0.05) with a slight increase of CD63, TSG101, and Rab27 in the presence of LPS. We found an enhanced and reduced migration rate in the LPS and SIM groups compared to the non-treated control cells (P<0.05). The expression of genes related to angiogenesis was down-regulated in both SIM and LPS groups.

Conclusion: These data indicate that the TLR4 signaling pathway can control the angiogenesis and Exo production in breast cancer cells, which paves the way for the development of de novo therapies in breast cancer patients.