Current Pharmaceutical Design - Volume 29, Issue 13, 2023

Rheumatoid arthritis (RA) is the most common form of the chronic inflammatory autoimmune disease characterized by chronic synovitis, synovial proliferation, and cellular infiltration. Further, it leads to bone erosion, destruction of articular cartilage, intense joint pain, swelling, and a high rate of disability, causing an immense load on human health. If the disease is identified early on, and the patient has continuous and timely treatment, many patients can achieve remission. Although research in RA has made considerable progress, conventional therapies are still the most popular treatment options for most people with RA. But, conventional therapies are hampered by various drawbacks, including higher doses, low solubility and permeability, poor bioavailability, a high level of first-pass metabolism, adaptive treatment tolerance (ATT), and long-term drug use. These drawbacks can result in severe side effects and drug toxicity in patients. Advances in polymer science and the application of nanotechnology in drug delivery systems have provided new possibilities in the treatment of RA by developing new-generation smart drug delivery systems (SDDSs). The shortcomings of non-specific drug distribution and uncontrollable drug release by traditional delivery systems have motivated the creation of next-generation SDDSs. These new smart drug delivery treatment methods have significantly changed the course of RA. Such systems can improve drug delivery by virtue of their multi-functionality and targeting capabilities. The ultimate objective of next-generation SDDSs is to deliver medication at the optimal time with precise dosage and efficiency and specificity to the targeted site (such as cells, tissues, and organs), which can aid patients to adhere better to their therapy. This review highlights and discusses the various next-generation SDDSs along with the conventional treatment options available for RA management.

The production of nanoparticles (NPs) from chemical and physical synthesis has ended due to the involvement of toxic byproducts and harsh analytical conditions. Innovation and research in nanoparticle synthesis are derived from biomaterials that have gained attention due to their novel features, such as ease of synthesis, low-cost, eco-friendly approach, and high water solubility. Nanoparticles obtained through macrofungi involve several mushroom species, i.e., Pleurotus spp., Ganoderma spp., Lentinus spp., and Agaricus bisporus. It is well-known that macrofungi possess high nutritional, antimicrobial, anti-cancerous, and immune-modulatory properties. Nanoparticle synthesis via medicinal and edible mushrooms is a striking research field, as macrofungi act as an eco-friendly biofilm that secretes essential enzymes to reduce metal ions. The mushroom-isolated nanoparticles exhibit longer shelf life, higher stability, and increased biological activities. The synthesis mechanisms are still unknown; evidence suggests that fungal flavones and reductases have a significant role. Several macrofungi have been utilized for metal synthesis (such as Ag, Au, Pt, Fe) and non-metal nanoparticles (Cd, Se, etc.). These nanoparticles have found significant applications in advancing industrial and bio-medical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and control the shape and size of nanoparticles. This review highlights various aspects of NP production via mushrooms, including its synthesis from mycelium and the fruiting body of macrofungi. Also, we discuss the applications of different technologies in NP high-scale production via mushrooms.

Coagulation activation is associated with cancer progression and morbidity. Recently, mechanisms through which coagulation proteases drive the tumor microenvironment (TME) have been elucidated. This review aims to develop a new strategy dependent on the coagulation system for treating osteosarcoma (OS). We focused on tissue factor (TF), the main initiator of the extrinsic coagulant pathway, as a target for OS treatment. It was found that cell surface-TF, TF-positive extracellular vesicles, and TF-positive circulating tumor cells could drive progression, metastasis, and TME in carcinomas, including OS. Thus, targeting tumor-associated coagulation by focusing on TF, the principle catalyst of the extrinsic pathway, TF is a promising target for OS.

It takes an average of 10-15 years to uncover and develop a new drug, and the process is incredibly time-consuming, expensive, difficult, and ineffective. In recent years the dramatic changes in the field of artificial intelligence (AI) have helped to overcome the challenges in the drug discovery pipeline. Artificial intelligence (AI) has taken root in various pharmaceutical sectors, from lead compound identification to clinical trials. Deep learning (DL) is a component of artificial intelligence (AI) that has excelled in many fields of Artificial intelligence (AI) research over the past decades. Its numerous applications in the realms of science and technology, especially in biomedicine and bioinformatics, are witnessed deep learning (DL) applications significantly accelerate drug discovery and pharmaceutical research in recent years, and their usefulness has exceeded expectations and shown good promise in tackling a range of issues with drug discovery. Deep learning (DL) holds great potential for drug development since it allows for sophisticated image interpretation, molecular structure and function prediction, and the automated creation of novel chemical entities with specific features. In the process of drug discovery, deep learning (DL) can be incorporated at all stages like identification of targets, prognostic biomarkers, drug designing and development, synergism and antagonism prediction, etc. This review summarizes various approaches of deep learning (DL) in drug discovery like deep generative models for drug discovery, deep learning (DL) tools for drug discovery, synergy prediction, and precision medicine.

Microsponges are polymeric delivery devices composed of porous microspheres that range in size from 5 to 300 micrometers. These have been explored for biomedical applications such as targeted drug delivery, transdermal drug delivery, anticancer drug delivery, and bone substitutes. The purpose of this study is to conduct a comprehensive analysis of recent developments and prospects for a microsponge-based drug delivery system. The current study analyzes how the Microsponge Delivery System (MDS) is made, how it works, and how it can be used for a wide range of therapeutic purposes. The therapeutic potential and patent information of microsponge-based formulations were systematically analyzed. The authors summarize various effective techniques for developing microsponges, such as liquid-liquid suspension polymerization, quasi-emulsion solvent diffusion method, water-in-oil-in-water (w/o/w) emulsion solvent diffusion, oil-in-oil emulsion solvent diffusion, lyophilization method, porogen addition method, vibrating orifice aerosol generator method, electrohydrodynamic atomization method, and ultrasound-assisted microsponge. Microsponge may reduce the side effects and increase drug stability by positively altering drug release. Drugs that are both hydrophilic and hydrophobic can be loaded into a microsponge and delivered to a specific target. The microsponge delivery technology offers numerous advantages over conventional delivery systems. Microsponges, which are spherical sponge-like nanoparticles with porous surfaces, have the potential to increase the stability of medications. They also efficiently decrease the undesirable effects and alter drug release.

Background: Curcumin is a main bioactive constituent of turmeric (Curcuma longa L.) with pleiotropic health beneficial effects. However, poor bioavailability is the major barrier to the efficient pharmacological effects of curcumin in humans. Aims: The present study aimed to develop liposome formulations based on soybean phosphatidylcholine (SPC) and hydrogenated SPC (HSPC) to enhance the bioavailability of curcumin in bladder cancer cells. Methods: Curcumin was encapsulated in HSPC and SPC liposome nanoparticles using the solvent evaporation method. Physical properties, encapsulation efficiency (%), stability, and in vitro drug release of the prepared liposome formulations have been evaluated. The cellular uptake and cytotoxicity of curcumin-encapsulated nanoliposomes on bladder carcinoma HTB9 cell line and normal fibroblast L929 cell line were studied. DNA fragmentation, apoptosis, and genotoxicity assessments have been carried out to determine the molecular mechanisms underlying the cytotoxic effects of liposomal curcumin formulations on bladder cancer cells. Results: The results indicated that curcumin could be efficiently encapsulated in the HSPC and SPC liposome formulations. The liposomal curcumin formulations have shown shelf-life stability for 14 weeks at 4°C. The accelerated stability testing showed that curcumin encapsulated in nanoliposomes was significantly (p < 0.001) more stable than free curcumin at various pH degrees ranging from alkaline to acidic pH. The in vitro drug release study showed curcumin to be sustainably released from the liposome nanoparticles. Of note, SPC and HSPC nanoliposome formulations significantly increased the cellular uptake and cytotoxicity of curcumin on bladder cancer HTB9 cells. Mechanistically, liposomal curcumin was found to exert a selective inhibitory effect on the viability of cancer cells by inducing apoptosis and DNA damage. Conclusion: In conclusion, SPC and HSPC liposome nanoparticles can significantly increase the stability and bioavailability of curcumin, which are important for improving its pharmacological effect.

Background: EpCAM and VEGFR2 play an important role in angiogenesis and tumorigenesis. It is currently of paramount importance to produce new drugs that can inhibit the angiogenesis and proliferation of tumor cells. Nanobodies are potential drug candidates for cancer therapy due to their unique properties. Objective: This study aimed to investigate the combined inhibitory effect of anti-EpCAM and anti-VEGFR2 nanobodies in cancer cell lines. Methods: Inhibitory activity of anti-EpCAM and anti-VEGFR2 nanobodies on MDA-MB231, MCF7, and HUVEC cells was investigated using both in vitro (MTT, migration, and tube formation assays) and in vivo assays. Results: Results showed that the combination of anti-EpCAM and anti-VEGFR2 nanobodies efficiently inhibited proliferation, migration, and tube formation of MDA-MB-231 cells compared to each individual nanobodies (p < 0.05). In addition, the combination of anti-EpCAM and anti-VEGFR2 nanobodies efficiently inhibited tumor growth and volume of Nude mice bearing MDA-MB-231 cells (p < 0.05). Conclusion: Taken together, the results indicate the potential of combination therapy as an efficient approach to cancer therapy.

An article was published in the journal "Current Pharmaceutical Design", Volume 9, No. 25, 2003, pp: 2078-2089 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/8545 We regret the error and apologize to readers.