Assay and drug development technologies最新文献

Chlorzoxazone (CHZ) is a centrally acting muscle relaxant used to treat muscle spasms. It is employed as a first-line medication for treating muscle spasms, offering both musculoskeletal relaxation and mild sedative effects. According to the biopharmaceutics classification system, it belongs to class II drug having poor solubility and high permeability. In order to improve the flow property, water solubility, and dissolution of CHZ, CHZ-nicotinamide (NA) cocrystal was prepared by liquid-assisted grinding cocrystallization (LAG CC) method using methanol as the choice of solvent. CHZ-NA cocrystal was characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry, and scanning electron microscopy (SEM). DSC scan showed a sharp endothermic peak shift, which is caused by the formation of a new crystal form with altered physical properties, which was further confirmed by PXRD. Also, a change in the surface morphology of LAG CC compared to CHZ was observed in SEM. The resultant CHZ-NA cocrystal displayed improved powder flow properties compared to the native form of CHZ. LAG CC demonstrated a 3.1- and 2.6-fold increase in saturated solubility and intrinsic dissolution rate, respectively, compared to CHZ alone. Furthermore, the in vitro dissolution study showed that the cumulative dissolution of CHZ in 2 h was about 53%. Whereas, dissolution of LAG CC reached 99% in 2 h, showing obvious dissolution improvement. Thus, CHZ-NA cocrystal could significantly improve the flow properties, solubility and dissolution of CHZ.

Androgen therapy has been shown to alleviate type 2 diabetes mellitus (T2DM) but is also associated with severe side effects such as prostate cancer. The present study aims to identify the best hit selective androgen receptor (AR) modulator by in silico studies and then investigates its antidiabetic effects in high-fat diet- and streptozotocin (STZ)-induced T2DM male rat model. Molecular docking and molecular dynamics (MD) studies were carried out using Maestro 13.1 and Desmond (2023-2024). Cytotoxicity and insulin secretion were measured in MIN6 cell lines. T2DM was induced using high-fat diet (HFD) for 4 weeks, followed by single STZ (40 mg/kg, intraperitoneally). OneTouch Ultra glucometer was used to measure fasting blood glucose. Gene expression was determined using reverse transcription polymerase chain reaction. Histopathology was carried out using hematoxylin and eosin stain. Through molecular docking, we identify ligandrol as a potential hit. Ligandrol showed a good binding affinity (-10.74 kcal/mol). MD showed that ligandrol is stable during the 100 ns simulation. Ligandrol increases insulin secretion in a dose-dependent manner in vitro in 2 h. Ligandrol (0.3 and 1 mg/kg, orally) significantly decreased the body weight and fasting blood glucose levels compared with the HFD and STZ group. Gene expression showed that ligandrol significantly increased the AR-targeted gene, neurogenic differentiation 1, compared with the HFD and STZ group. Histopathological staining studies showed that ligandrol prevents pancreatic islet degeneration compared with the HFD and STZ group. Our findings suggest that ligandrol's protective effect on pancreatic islets leading to its antidiabetic effect occurs through the activation of AR.

This study aimed to assess the synergistic antioxidant and anticancer effects of methanolic extracts derived from Rubus ellipticus and Boerhavia diffusa fruits against the HeLa cell line. The methanolic extracts were prepared from the fruits of R. ellipticus and B. diffusa, and their antioxidant potential was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity assay and the ferric reducing antioxidant power (FRAP) assay. The anticancer effects of benzoic acid and rutin extracted from the aforementioned fruits were also investigated against the HeLa cell line using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay to measure the cell metabolic activity. Using Synergy Finder plus software, the bioactive compounds were tested to explore any synergistic effects. R. ellipticus exhibited higher antioxidant potential as revealed by higher DPPH scavenging activity and FRAP value compared with B. diffusa. The benzoic acid extracted from R. ellipticus demonstrated potent anticancer activity against the HeLa cell line, with an IC₅₀ of 1.07 µg/mL. Similarly, rutin extracted from B. diffusa displayed moderate anticancer activity with an IC₅₀ of 1.4 µg/mL while exhibiting minimal impact on normal cell lines. The combination studies of the extracted bioactive compounds revealed a synergistic effect. These findings suggest the therapeutic potential of R. ellipticus and B. diffusa in combating the oxidative stress and cancer. Their bioactive compounds like benzoic acid and rutin were observed to act synergistically. Further investigations are warranted to elucidate the underlying mechanisms and evaluate their applicability in clinical settings.

As one of the primary causes of illness and death globally, cancer demands novel and potent treatment approaches, which is why lipid nanoparticles (LNPs) have gained attention as a promising delivery system for anticancer drugs with precision and efficacy. The article discusses the salient characteristics of LNPs, such as the lipid components, particle size, polydispersity index, and encapsulation efficiency, followed by strategies that enhance their remarkable drug delivery capabilities. The articles explore LNPs ability to improve the solubility, stability, and bioavailability of various chemotherapeutics, nucleic acids, and immunotherapeutic modalities. It also highlights the recent advancement in surface modification of LNPs, which is essential to improve their effectiveness. Tailored coatings of LNPs improve targeting precision, stability, and biocompatibility; enhancing their transport to boost therapeutic efficacy for cancer targeting. The review summarizes the recent advancements made in using LNPs to treat different forms of cancer and focuses on the most recent clinical studies. Overall, the review highlights that the LNPs can target and treat cancer in a tailored manner through gene therapy, RNA interference, and immunotherapy.

The objective of the present study was to optimize the microwave-assisted synthesis of the acrylamide graft copolymer of Acacia nilotica gum (AM-co-ANG). Furthermore, graft copolymer was used for the formulation of a nanoparticulate system using a novel top to bottom solvent antisolvent technique for the delivery of melatonin. Grafting of ANG was optimized by using 3² factorial design, where concentrations of polymer and monomer (acrylamide) were used as independent variables and swelling index in acidic (0.1 N HCl) and basic (1 N NaOH) pH. Grafted polymers were further used to develop and optimize nanoparticulate system using concentration of the graft copolymer and concentration of drug as independent variables. The size of the nanoformulation and entrapment efficiency were selected as dependent variables. Difference in infrared spectrum and absorbance maxima in the ultraviolet region confirm that grafting has taken place. Porous structure and a higher contact angle confirmed hydrophobic nature of AM-co-ANG as compared with the native polymer. Acrylamide graft copolymers show more swelling in 1 N NaOH as compared with 0.1 N HCl. In vitro toxicity studies in hepatic (HepG2 cell line), brain (SHSY5Y cell line), and skin (HaCaT cell line) cells easily predict that synthesized polymer have no cytotoxicity. The entrapment efficiency ranged from 55.24 ± 1.35% to 73.21 ± 1.83%. A nonlinear correlation was observed between independent and dependent variables, as confirmed by multivariate analysis of variance, surface regression, and the correlation report. The prepared formulations were able to release drug up to 12 h. The regression coefficient easily predicted that most of the formulations followed Baker-Lonsdale drug release kinetics.