Current Pharmaceutical Design - Volume 30, Issue 28, 2024

Over the period of the preceding decade, artificial intelligence (AI) has proved an outstanding performance in entire dimensions of science including pharmaceutical sciences. AI uses the concept of machine learning (ML), deep learning (DL), and neural networks (NNs) approaches for novel algorithm and hypothesis development by training the machines in multiple ways. AI-based drug development from molecule identification to clinical approval tremendously reduces the cost of development and the time over conventional methods. The COVID-19 vaccine development and approval by regulatory agencies within 1-2 years is the finest example of drug development. Hence, AI is fast becoming a boon for scientific researchers to streamline their advanced discoveries. AI-based FDA-approved nanomedicines perform well as target selective, synergistic therapies, recolonize the theragnostic pharmaceutical stream, and significantly improve drug research outcomes. This comprehensive review delves into the fundamental aspects of AI along with its applications in the realm of pharmaceutical life sciences. It explores AI's role in crucial areas such as drug designing, drug discovery and development, traditional Chinese medicine, integration of multi-omics data, as well as investigations into drug repurposing and polypharmacology studies.

When compared to the challenges associated with traditional dosage forms, medication delivery systems based on nanotechnology have been a huge boon. One such candidate for medication delivery is spanlastics, an elastic nanovesicle that can transport a diverse array of medicinal compounds. The use of spanlastics has been associated with an increase in interest in alternative administration methods. The non-ionic surfactant or surfactant blend is the main component of spanlastics. The purpose of this review was primarily to examine the potential of spanlastics as a delivery system for a variety of medication classes administered via diverse routes. Science Direct, Google Scholar, and Pubmed were utilized to search the academic literature for this review. Several studies have demonstrated that spanlastics greatly improve therapeutic effectiveness, increase medication absorption, and decrease drug toxicity. This paper provides a summary of the composition and structure of spanlastics along with their utility in the delivery of various therapeutic agents by adopting different routes. Additionally, it provides an overview of the numerous disorders that may be treated using drugs that are contained in spanlastic vesicles.

Background: Cannabidiol (CBD) is the principal non-hallucinogenic compound of Cannabis plants with high clinical interest because CBD has been described as having anti-inflammatory, analgesic and anticonvulsant properties. CBD is considered a multitarget compound as it can interact with a wide range of targets, explaining their multiplicity of effects. Some clinical studies have indicated certain side effects of CBD, including somnolence, anemia and diarrhea, while the elevation of transaminases is considered as an exclusion criterion from the trial. Since the red blood cells (RBCs) are a source of transaminase, we assayed in vitro effect on RBCs stability. Methods: We performed in vitro experiments with RBCs obtained from human peripheral blood with normal hematological parameters exposed to CBD in the range of therapeutic uses. We evaluated RBCs morphological changes, membrane fragility and hemoglobin release as a reflection of hemolysis. Results: CBD induced an increase in the hemoglobin release (3.27 μg/10⁶ RBC), without altered RBC osmotic fragility. When RBCs suspensions were incubated with CBD the initial number of elements (RBCs + vesicles) was increased up to 65% after 20 min and returned to basal level after 40 min of incubation. In the first 20 min, the accounts of elements were enriched in the smaller vesicles that disappeared after the remaining 20 minutes. Conclusion: These results suggest that CBD affects the indemnity of erythrocytes in vitro, inducing the formation of hemolytic vesicles that can provide the basis for the development of anemia, transaminase elevation and underlying tissular iron overload in patients chronically treated with CBD.

Background: Neuroinflammation is the pathological basis of many neurological diseases, including neurodegenerative diseases and stroke. Hua-Feng-Dan (HFD) is a well-established traditional Chinese medicine that has been used for centuries to treat stroke and various other brain-related ailments. Objective: Our study aims to elucidate the molecular mechanism by which HFD mitigates neuroinflammation by combining network pharmacology and in vitro experiments. Methods: TCMSP and SymMap databases were used to extract active compounds and their related targets. The neuroinflammation-related targets were obtained from the GeneCards database. The common targets of HFD and neuroinflammation were used to construct a protein-protein interaction (PPI) network. MCODE plug-in was used to find the hub module genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to dissect the hub module genes. The lipopolysaccharide (LPS)-induced BV2 microglial neuroinflammation model was utilized to assess the therapeutic effects of HFD on neuroinflammation. Western blotting analysis was performed to examine the core target proteins in the TLR4/My- D88/NF-ΚB signaling pathway, potentially implicated in HFD's therapeutic effects on neuroinflammation. Hoechst 33342 staining and JC-1 staining were employed to evaluate neuronal apoptosis. Results: Through network pharmacology, 73 active compounds were identified, with quercetin, beta-sitosterol, luteolin, and (-)-Epigallocatechin-3-Gallate recognized as important compounds. Meanwhile, 115 common targets of HFD and neuroinflammation were identified, and 61 targets were selected as the hub targets utilizing the MCODE algorithm. The results of in vitro experiments demonstrated that HFD significantly inhibited microglial-mediated neuronal inflammation induced by LPS. Integrating the predictions from network pharmacology with the in vitro experiment results, it was determined that the mechanism of HFD in mitigating neuroinflammation is closely related to the TLR4/MyD88/NF-ΚB pathway. Furthermore, HFD demonstrated the capacity to shield neurons from apoptosis by curbing the secretion of pro-inflammatory factors subsequent to microglial activation. Conclusion: The findings demonstrated that HFD had an inhibitory effect on LPS-induced neuroinflammation in microglia and elucidated its underlying mechanism. These findings will offer a theoretical foundation for the clinical utilization of HFD in treating neurodegenerative diseases associated with neuroinflammation.

Background: In recent years, the incidence and prevalence of Nephrotic Syndrome (NS) have been increasing. Zhuling Decoction (ZLD), a classical Chinese medicine, has been clinically proven to be effective for the treatment of NS. However, its underlying mechanism and pharmacodynamic substances remain unclear. Objective: This study aimed to explore the mechanism of action and chemical components of ZLD against NS using network pharmacology and molecular docking. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicines (BATMAN-TCM), and SwissTargetPrediction databases were used to screen the principal ingredients and the associated targets of ZLD. NS-related targets were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), and Drugbank databases. Shared targets were derived by the intersection of ZLD- and NS-associated targets. Protein-interaction relationships were analyzed using the STRING database and Cytoscape. A visualized drug-active compound-target network of ZLD was established using Cytoscape. Analyses of gene enrichment were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed to assess the binding activity between active components and hub targets. Results: Polyporusterone E, cerevisterol, alisol B, and alisol B 23-acetate were the primary potential ingredients of ZLD. HMGCR, HSD11B1, NOS2, NR3C1, and NR3C2 were the hub targets of ZLD against NS. Molecular docking showed that polyporusterone E, cerevisterol, and alisol B had high binding activities with targets HMGCR, HSD11B1, and NOS2. Conclusion: In summary, this study suggests that the main active compounds (polyporusterone E, cerevisterol, alisol B) may have important roles for ZLD acting against NS by binding to hub targets (HMGCR, HSD11B1, and NOS2) and modulating PI3K-Akt, Ras, MAPK, and HIF-1 signaling pathways.

Introduction: A sustained release system for losartan potassium designed to delay its residence time in the stomach through the preparation of solvent evaporation technique-based floating microspheres. The influence of the different grades of Ethocel™ such as 4 cps, 10 cps, and 22 cps as well as the drug: polymer ratio on various properties of microspheres were tested. Methods: Thermal and functional analysis revealed no interaction between the encapsulated drug and polymer. The results indicated that the mean diameter of microspheres increased with a change in grades of ethyl cellulose relating to viscosity. However, the drug incorporation efficiency within ethyl cellulose microspheres decreased with increasing viscosity of ethyl cellulose. Results: The bulk density of the formulations was proportionally dependent on concentration and the viscosity of the polymer, which resulted in a decrease in floating capacity from 90.02% to 73.58%. Moreover, the drug release was indirectly proportional to the viscosity of ethyl cellulose tested. The in vitro release profile exhibited a burst effect with a biphasic release pattern following Fickian diffusion, indicating a diffusioncontrolled release mechanism. Conclusion: The results demonstrated that the viscosity of ethyl cellulose significantly affects the floating capacity and drug release pattern from microspheres.