Assay and drug development technologies最新文献

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.

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.

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.

To enhance brain delivery of efavirenz (EFV), optimized nanostructured lipid carriers (NLCs) were developed using a melt-emulsification technique and probe sonication. Box-Behnken design was chosen to systematically analyze the effects of variables on formulation outcomes, enabling efficient optimization with fewer experimental trials. This selection helped to improve the formulation by allowing us to refine key characteristics such as particle size, entrapment efficiency, and polydispersity index (PDI). The optimized EFV-NLCs had a mean particle size of 91.41 ± 7.90 nm, a PDI of 0.28 ± 0.04, a zeta potential of -17 mV, an entrapment efficiency of 85 ± 7%, and a drug loading of 14 ± 1%. Transmission electron microscopy confirmed that the EFV-NLCs were spherical with uniform size distribution. In vitro release tests showed prolonged drug release, with release rates ranging from 63.09 ± 2.76% to 84.43 ± 4.24% at pH 1.2 and 87.66 ± 6.31% to 92.56 ± 1.48% at pH 6.8. This was significantly better than the EFV suspension, which showed moderate and unsustainable release rates over 8 h. Furthermore, dissolution studies in both fasted and fed state simulated-intestinal-fluids (FaSSIF and FeSSIF) over 6 h revealed that % cumulative drug release was significantly higher in FeSSIF (94.06 ± 1.62%) compared with FaSSIF (65.21 ± 3.95%), indicating enhanced absorption in the presence of food. In vitro gut permeation studies revealed that EFV-NLCs had a 2.05-fold higher drug permeability than the suspension. These findings suggest that EFV-NLCs are promising for targeted brain delivery, are safe for oral administration, and could be instrumental in managing neuro-acquired immunodeficiency syndrome.

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.

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.