Assay and drug development technologies最新文献

Muscle strain is one of the most common injuries with high intermittence rate. Due to diverseness of strain injuries, different experimental animal models are employed to investigate such injuries with reproducible results. Cubosomes, an emerging nano drug delivery tool, are considered ideal carriers for the topical delivery of lipophilic drugs to treat local inflammations with reduced frequency of application for prolonged periods. This work describes the development of Felbinac-loaded cubosomal gel and investigated the treatment of inflammation and tissue injury in vivo. Sciatic Function Index (SFI) is a simple clinical method to observe hind limb recovery in rats after induced injuries. First, cubosomes were fabricated by high-pressure homogenization process and evaluated for in vitro parameters. The optimized cubosome formulation was chosen to develop cubosomal gel and evaluated for in vitro parameters and also investigated time to recovery of SFI after strain induction in tibialis anterior muscles in rats. The cubosome formulation (F4) exhibited low droplet size (51.04 ± 1.37 nm)and polydispersity index (0.085 ± 1.13), and negative zeta potential (-32.8 ± 0.67 mV). In rats, topical application of cubosomal gel formulation (CGF) exhibited significant improvement in skin permeation (402 ± 6.08 μg) and drug flux (15.71 ± 0.82 μg/cm² h) compared to plain gel. Also, CGF demonstrated significant difference in SFI from first to seventh day. The histology of rat skin showed significant effect for groups treated with Felbinac-loaded CGF compared to a negative control group.

Propolis is rich in natural bioactive compounds, and considering its importance for many skin therapies, emulgel was prepared. This study examines how a propolis extract (PE) and Passiflora edulis seed (PS) oil emulgel affect rat deep skin wound healing. Based on preset criteria of maximum drug content and optimum drug permeation through the stratum corneum along with drug retention in the skin layers, an optimized emulgel formula based on Box-Behnken factorial design was prepared and used for subsequent in vitro and in vivo evaluations. In vivo wound-healing activities of emulgel and control treatments were investigated in a rat model. The optimized emulgel formula exhibited superior healing activity compared with plain PE suspension-treated rats on day 14 of wounding. Histopathological investigations of hematoxylin and eosin and Masson's Trichrome-stained skin sections supported this effect. Emulgel promotes cutaneous wound healing through a variety of mechanisms, including anti-inflammatory through modulation of cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 production, and promotion of collagen fiber formation, all of which contribute to tissue remodeling. Furthermore, when compared with propolis suspension, emulgel showed significant antioxidant and anti-inflammatory effects. Emulgel significantly increased the skin's hydroxyproline level, antioxidant potential, wound contraction, increased penetration, and localized propolis deposition across the skin. Incorporation of PS oil into the emulgel accelerates the tissue regeneration process. The findings suggest that 5% propolis emulgel could be used as an alternative to treat wounds.

One of the most sought-after therapeutic targets for treating human cancers is the phosphoinositide 3-kinase; PI3k is an integral part of the PI3K/protein kinase B signaling arcade. This pathway is frequently activated in malignancies. Drug resistance and dose-limiting adverse effects are currently associated challenges with the existing anticancer chemotherapy. Therefore, in this research, a series of pyrimidine derivatives were designed and evaluated against human PI3K by using molecular docking analysis. The docking results were further verified by molecular dynamic simulation, which analyzed the strength of the macromolecular complex with respect to time. Compounds IV and XIV were found to be the most potent inhibitors of the human PI3K receptor with a high degree of stability within the active site of the target receptor for a timeframe of 50 ns. Thus, both of these compounds could be important drug candidates for the development of PI3K inhibitors as a prospective anticancer agent.

Azithromycin (AZI) belongs to the class of macrolide antibiotics that has limited water solubility and belongs to Biopharmaceutical Classification System Class II. Dissolution is the rate-limiting step in the absorption process of AZI. Several approaches have been investigated for enhancing the bioavailability of poorly soluble drugs. This review intends to explore the various strategies that have been investigated for improving the solubility and/or bioavailability of AZI and the delivery systems that have been designed for delivery of AZI in ocular fluid.

Drug-resistant infections have become a serious threat to human health in the past two decades. Global Antimicrobial Surveillance (GLASS) in January 2018 reported widespread antibiotic resistance among 1.5 million people infected with bacteria across 22 countries. According to prominent economist Jim O'Neil, antimicrobial resistance is estimated to kill ∼10 million people affected by microorganisms each year by 2050. Even though multiple therapeutics are now available to treat the infections, more and more bacterial strains have acquired resistance to these treatments through various techniques. Moreover, the decrease in the pipeline of antibacterial medicines under clinical development has become a significant problem. In this scenario, the development of novel antibiotics that act on untapped pathways is necessary to combat the bacterial infections. Isoprenoid H (IspH) synthetase has become an attractive antibacterial target as there is no human homologue. IspH is an enzyme involved in methyl-d-erythritol phosphate (MEP) pathway of isoprenoid synthesis and is conserved in gram-negative bacteria, mycobacteria, and apicomplexans. Since, IspH is a novel therapeutic target, explorations are only just beginning, and despite the progress made in this area, no single IspH inhibitor is available in the market for therapeutic use. In this article, we have repurposed 35 immune boosters against IspH enzyme using methods such as extra-precision docking and Molecular Mechanics Generalized Born Surface Area (MMGBSA). Among them, 4'-fluorouridine was found to be active because of its glide score and significant binding affinity with IspH enzyme. Furthermore, this study requires more in vitro, in vivo, and molecular dynamics studies to support our findings.

Intranasal route provides large surface area, avoids first-pass metabolism, and results in improved drug absorption. Intranasal delivery targets the drug to the brain for treatment of central nervous diseases viz migraine. The objective of the study was to formulate in situ nasal gel containing rizatriptan benzoate (RB)-loaded nanostructured lipid carriers (NLCs). NLCs were prepared by melt-emulsification ultrasonication method and optimized using 3² factorial design. Optimized NLCs were spherical with particle size of 189 nm, high drug encapsulation efficiency (84.5%), and 83.9% drug release at the end of 24 h. RB-loaded NLCs were incorporated into the liquid Carbopol 934P and Poloxamer 407 liquid gelling system to obtain in situ gel formation. The resultant product was assessed for gelling capacity, viscosity, and mucoadhesive strength. In vivo pharmacokinetic studies revealed significant therapeutic concentration of drug in the brain following intranasal administration with C_max value of 5.1 ng/mL and area under the curve value of 829 ng/(min·mL). Significantly higher values of nose to brain targeting parameters, namely, drug targeting index (2.76) and nose to brain drug direct transport (63.69%) for RB-NLCs in situ nasal gel, confirmed drug targeting to brain through nasal route. The ex vivo nasal toxicity study showed no sign of toxicity to the nasal mucosa. Thus, the application of lipid carrier-loaded in situ gel proved potential for intranasal delivery of RB over the conventional gel formulations for efficient brain targeting.