Assay and drug development technologies最新文献

Antimicrobial resistance in disease-causing microbes is seen as a severe problem that affects the entire world, makes therapy less effective, and raises mortality rates. Dermal antimicrobial therapy becomes a desirable choice in the management of infectious disorders since the rising resistance to systemic antimicrobial treatment frequently necessitates the use of more toxic drugs. Nanoparticulate systems such as nanobactericides, which have built-in antibacterial activity, and nanocarriers, which function as drug delivery systems for conventional antimicrobials, are just two examples of the treatment methods made feasible by nanotechnology. Silver nanoparticles, zinc oxide nanoparticles, and titanium dioxide nanoparticles are examples of inorganic nanoparticles that are efficient on sensitive and multidrug-resistant bacterial strains both as nanobactericides and nanocarriers. To stop the growth of microorganisms that are resistant to standard antimicrobials, various antimicrobials for dermal application are widely used. This review covers the most prevalent microbes responsible for skin and soft tissue infections, techniques to deliver dermal antimicrobials, topical antimicrobial safety concerns, current issues, challenges, and potential future developments. A thorough and methodical search of databases, such as Google Scholar, PubMed, Science Direct, and others, using specified keyword combinations, such as "antimicrobials," "dermal," "nanocarriers," and numerous others, was used to gather relevant literature for this work.

Ulcerative colitis (UC) is a chronic inflammatory colon disorder. Several modern medicines have been used for UC treatment but are associated with side effects. Hence, herbal medicine-inspired lead molecules are promising for managing UC. Chlorogenic acid (CGA), an herbal bioactive, has been reported for anti-inflammatory, anticancer, antioxidant, and immunomodulatory activity. The current study aimed to develop enteric-coated mucoadhesive beads of CGA for colon targeting. CGA-loaded beads were prepared using chitosan and carrageenan as polymers through an ionic gelation technique. Furthermore, beads were coated with Eudragit S-100. The formulations were characterized by particle size analyzer, ultraviolet (UV)-spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and in vitro drug release study. The optimized formulation (CGA-F2) showed particle size (440.6 ± 6.1 μm), zeta potential (-31.12 ± 2.16 mV), entrapment efficiency (83.56 ± 5.46), %yield (86.87 ± 4.19), and drug loading (1.14 ± 0.09). SEM indicated that the morphologies of CGA-F2 were spherical and ellipsoidal. The FTIR study confirmed the compatibility of the drug with polymers used in the formulations. CGA-F2 exhibited mucoadhesive efficiency (94.33 ± 2.1%) and swelling index (0.98 ± 0.03) at simulated colonic fluid (SCF) pH 7.4 (***p < 0.001) significantly. In an in vitro drug release study, CGA-F2 (95.07 ± 3.85%) showed a sustained drug release profile in SCF (pH 7.4) at 37 ± 0.5°C for 24 h. Optimized formulation exhibited drug release in a sustained manner for 24 h, which may be due to the effect of mucoadhesive and enteric coating polymer. Hence, CGA-loaded beads would be promising for treating the UC.

Gold nanoparticles (AuNPs), due to their unique properties and surface modification abilities, have become a promising carrier for a range of biomedical applications. AuNPs have intrinsic antiviral characteristics because of their capacity to enhance drug distribution by making antiviral medications more stable and soluble, which assures that higher quantities reach the intended site. Through surface changes, AuNPs can bind directly to viral particles or infected cells, increasing therapeutic efficiency and reducing side effects. AuNPs efficiently damage cell membranes and hinder viral reproduction within a host cell. Furthermore, because of their large surface area-to-volume ratio, which enables many functional groups to connect, improving interaction with virus particles and ceasing their multiplication. By altering dimensions and morphology or conjugating it with additional antiviral drugs, AuNPs can array their synergistic antiviral activity. Thus, the development of AuNP conjugated therapy presents a promising avenue to address the demand for novel anti-viral therapeutics against infections resistant to several drugs.

Melanoma, a highly aggressive form of skin cancer, presents a formidable challenge in terms of treatment due to its propensity for metastasis and resistance to conventional therapies. The development of innovative nanocarriers for targeted drug delivery has opened new avenues in cancer therapy. Lactoferrin-conjugated extracellular nanovesicles (LF-EVs) have emerged as a promising vehicle in the targeted treatment of cellular melanoma, owing to their natural biocompatibility, enhanced bioavailability, and ability to traverse biological barriers effectively. This review synthesizes recent advancements in the use of LF-EVs as a novel drug delivery system for melanoma, emphasizing their unique capacity to enhance cellular uptake through LF's receptor-mediated endocytosis pathways. Key studies demonstrate that LF conjugation significantly increases the specificity of extracellular nanovesicles for melanoma cells, minimizes off-target effects, and promotes efficient intracellular drug release. Furthermore, we explore how LF-EVs interact with the tumor microenvironment, potentially inhibiting melanoma progression and metastasis while supporting antitumor immune responses. Future prospects in this field include optimizing LF conjugation techniques, improving the scalability of LF-EV production, and integrating multifunctional payloads to target drug resistance mechanisms. This review highlights the potential of LF-EVs to transform melanoma treatment strategies, bridging current gaps in therapeutic delivery and paving the way for personalized and less invasive melanoma therapies.

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.

The primary objective of the present investigation is to develop and validate a simple, robust, and cost-effective isocratic reverse phase-high-performance liquid chromatography (RP-HPLC) method for determining isoliquiritigenin (ISL) in both bulk and biological samples using an analytical quality-by-design (AQbD) approach. The central composite design was employed for method optimization using Design Expert® software, by taking mobile phase ratio and flow rate as independent variables and peak area, retention time, tailing factor, and theoretical plates as dependent variables. The design suggested the use of a mobile phase consisting of acetonitrile:0.2% ortho-phosphoric acid (75:25, v/v) and a flow rate of 0.9 mL/min as optimal chromatographic conditions. The detection of ISL was performed at 364 nm. The optimized method was validated in accordance with International Conference on Harmonization (ICH) Q2(R1) guidelines. The method showed excellent linearity, limit of detection, limit of quantification, accuracy, precision, robustness, and system suitability. All validation parameters fell within the acceptable limits set by ICH. Additionally, the applicability of the method in biological samples were analyzed. In conclusion, the results suggest that the developed and validated AQbD-based RP-HPLC method was well-suited for the estimation of ISL in bulk and biological sample.

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.

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.