Assay and drug development technologies最新文献

The present study highlighted enhancing the therapeutic effectiveness of curcumin (CUR) co-loaded lawsone (LS) through a solid lipid nanoparticles (SLNs)-based delivery system. The cetyl palmitate (CP), polyethylene glycol 400 (PEG), and probe sonication time (PS) were considered as independent variables whereas particle size and % entrapment efficiency (EE) were selected as dependent variables. The CUR-LS-SLN was developed by hot emulsification followed by probe sonication. A 2³ factorial design was utilized in formulation development using JMP software version 17. Notably, the particle size and %EE of all the formulations were about 500 nm and greater than 75%, respectively. The zeta potential value was found to be -46.8 mV. From leverage plots significant and sensitive factors on particle size and %EE were identified. Contour plots led to the identification of an optimized formula whereby maintaining CP at 100 mg, PEG 400 at 6 mL, and PS at 10 min the desired particle size and %EE was achieved. TEM studies indicated the spherical shape of the particles. MTT assays of Michigan Cancer Foundation-7 (MCF-7) cells showed enhanced efficacy and greater cell inhibition of CUR-LS-SLN and combining both drugs using nanocarriers gave superior inhibition as compared with using either of the drugs evident from IC₅₀ values of 3.7, 9.4, and 2.5 μM, respectively, for CUR, LS, and CUR-LS-SLN. The cells in the combination mostly had irregular cell walls and cell shrinkage was noted and greater cell reduction was also seen. It was found that the enhanced cytotoxicity effect of MCF-7 cells on the developed formulation was attributed to the drug's synergistic actions, more efficient nanocarrier internalizations, and sustained drug release from the formulation. Stability studies indicated that the optimized SLN was stable for 6 months.

Methotrexate (MTX) is an effective anticancer agent with limited water solubility, resulting in lower absorption in the gastrointestinal tract when administered orally. The present aim of the study is to construct sustained-release formulation of MTX-loaded microsponges with enhanced intestinal absorption and bioavailability using a quasi-emulsion solvent diffusion method. The Box-Behnken design (BBD) was adopted for this purpose. Particle size, encapsulation efficiency (EE), Q 2 h % (% drug release in 2 h), and Q 24 h % (% drug release in 24 h) were used as dependent factors, and polyvinyl alcohol, solvent, and stirring speed were used as independent factors. The prepared microsponges were characterized to assess their particle size and encapsulation efficacy (%). Attenuated total reflectance-Fourier transform infrared spectroscopy and differential scanning calorimetry were used to verify the compatibility study. Moreover, the cytotoxicity study was conducted on the HT-29 cell line. The optimized formulation exhibited a % encapsulation efficacy of 87.191% and a particle size of 2.176 µm. Furthermore, the optimized formulation demonstrated sustained drug release (85.71%) in Simulated Gastric Fluid (SGF) fluid at different pHs 1.2, 6.8, and 7.4. The stability study of the optimized formulation revealed good stability in terms of drug release, % encapsulation efficacy, and particle size. The results of the optimized formulation demonstrated that the viability of HT-29 colon cancer (CC) cells was dose-dependently decreased by MTX-loaded microsponges. BBD was successfully employed for the development and optimization of MTX microsponges filled in Eudragit S-100-coated hard gelatin capsule, depicting their potential release of MTX from microsponges capsule only at the colonic region and found to be potential carrier system for CC.

This study aimed to elucidate the hepatoprotective mechanisms of microalgal fatty acids (MFA) from Schizochytrium against alcoholic liver disease (ALD) through network pharmacology and in vivo analysis. Network pharmacology and molecular docking methodologies were employed to predict the potential mechanisms of MFA against ALD. To substantiate these predictions, an acute alcoholic liver injury mouse model was utilized to assess the impact of MFA on serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total protein (TP), and albumin (ALB). Additionally, liver histopathology and the expression levels of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) protein were evaluated. Seven active ingredients and 53 potential targets (including 7 core targets) for ALD treatment were identified in MFA. Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these seven core targets are implicated in various biological pathways, notably those associated with cancer, viral infections, and the PI3K/AKT signaling pathway. Furthermore, molecular docking studies demonstrated that docosahexaenoic acid and docosapentaenoic acid in MFA exhibited strong binding affinity for these seven crucial targets. Animal experiments demonstrated that administration of MFA significantly decreased the levels of AST, ALT, and ALP, while increasing the levels of ALB and TP in mice with acute alcoholic liver injury. Moreover, MFA ameliorated liver tissue pathology and markedly down-regulated the expression of PI3K and AKT proteins in the liver. These results suggest that MFA may possess therapeutic potential for ALD by targeting multiple pathways, with its mechanisms likely involving the inhibition of the PI3K/AKT signaling pathway.

Viral diseases remain a significant challenge for global health with rising fatalities each year. In vitro assays are crucial techniques that have been utilized by researchers in the quest to develop antiviral therapies. These assays mimic the internal conditions of a living system and make it possible to study how antiviral compounds interact with such systems in a laboratory setting. Thus, the importance of in vitro assays cannot be overemphasized, as they provide an accurate means for assessing the efficacy of potential antiviral compounds. This review offers an overview of in vitro antiviral assays, the different types of cell lines used, and emerging techniques and applications that have been developed in recent times. The current review also assesses challenges that are encountered in antiviral drug research, as well as emerging technologies like microfluidics and three-dimensional cell cultures. The integration of computational models and multiparametric assays into antiviral research was noted to significantly improve antiviral drug development process.

The skin is a dynamic tissue that consists of different layers such as stratum corneum, the site for keratinocyte development and maturation for the natural changeover of skin. In psoriasis, this natural development of keratinocytes gets disturbed and aggregation of nucleated keratinocytes takes place in the epidermis of the skin, leading to the presence of scaly skin, which makes the patient physically, socially, and psychologically ill. Various natural, semisynthetic, and synthetic treatments are available. Still, semisynthetic or synthetic are mainly used to treat psoriasis with side effects on different parts of the body, which is life threatening. Various molecular target sites are getting upregulated such as Janus kinase/Signal transducer and activator of transcription (JAK/STATs), phosphodiesterase 4 (PDE4), mitogen-activated protein kinase (MAPK), platelet selectin (Pan Selectin), Tumor Necrosis Factor Alpha (TNF-α), Interleukin-23 (IL-23), Interleukin-17 (IL-17), and Tyrosine Kinase 2 (Tyk2) in psoriasis. Plants and their bioactive compounds of flavonoids, alkaloids, resins, tannins, glycosides, and terpenoids category are used in the treatment of psoriasis as topical, oral, and biological forms. Using a computational approach, the inhibition of these molecular targets can be studied and potential molecules can be identified. This research article aims to find out the potential molecules that can inhibit the molecular sites and are effective than synthetic ones.

To optimize the formulation of docetaxel-zedoary oil magnetic solid lipid nanoparticles (DTX-ZTO-MSLN) using central composite design-response surface methodology. First, the formulation and preparation process of DTX-ZTO-MSLN were optimized via design-response surface methodology. The appearance, particle size, thermogravimetric, pH, iron content, magnetic strength, and in vitro drug release of DTX-ZTO-MSLN were subsequently examined. Finally, the antitumor effect of DTX-ZTO-MSLN on MCF-7 breast cancer cells was measured via the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The optimized formulation was as follows: the mass ratio of soybean phospholipid to poloxamer 188 was 0.34, the mass ratio of DTX-ZTO to glycerol monostearate was 3.23, and 29.42 mL of water was used. The DTX-ZTO-MSLN prepared by the optimized method was clear and transparent, with good stability, with an iron content of 7.38%, and a saturation magnetization intensity of 7.05 A·m²·kg^-1. The in vitro drug release was consistent with the Weibull model (R² = 0.9992). Compared with zedoary turmeric oil and docetaxel, DTX-ZTO-MSLN had a much greater inhibitory effect on MCF-7 cells (p < 0.05). The optimized DTX-ZTO-MSLN meets the quality requirements for nanoemulsions. This study provides a theoretical basis for developing and applying DTX-ZTO-MSLN.

Skin is one of the largest organs in the human body. It acts as an outer protective cover and comprises the epidermis, dermis, and hypodermis. Liposomes are formed by phospholipids and have a vesicular character that improves the encapsulation of lipophilic, hydrophilic, and amphiphilic drugs. The invasome structure is flexible as opposed to regular liposomes; this is due to the presence of ethanol and terpene that increases lipid fluidity in the vesicle structure. Terpenes, ethanol, or terpene mixes are potential carriers that invasomes' tiny liposomal vesicles used to improve skin penetration. Terpenes that are primarily derived from natural sources are the most efficient and secure kind of penetration enhancers (PEs). There are some methods for the preparation of invasomes, but mostly the techniques used for the preparation of invasomes are mechanical dispersion and film hydration methods. Although PEs are effective when applied topically, only a small number are clinically approved due to concerns about skin irritation and toxicity. Invasomes exhibit a higher rate of skin penetration than liposomes and ethosomes. This review examines the structure, components, preparation methods, and applications of invasomes in pharmaceutical formulations, focusing on their potential to treat skin disorders and improve therapeutic outcomes. The primary objective is to assess the future potential of invasome technologies in transdermal drug delivery, alongside an exploration of the regulatory challenges and pathways for their development and approval. Graphical abstract illustrating the composition, mechanism of action, and therapeutic applications of invasomes in transdermal drug delivery systems.