Assay and drug development technologies最新文献

Diabetes mellitus (DM) is the most common endocrine disorder characterized by increased blood glucose levels resulting from defective insulin secretion, resistance to insulin action, or both. DM is often associated with severe complications, and there is an increasing appreciation that cognitive function declines in DM. The aim of this research work was to evaluate Kigelia pinnata root bark extract in Streptozotocin (STZ)-induced type-2 diabetes. Experimental diabetes was induced by a single administration of STZ (60 mg/kg, intraperitoneal [i.p.]), immediately after the STZ administration, and all animals were fed with normal food and water. Nicotinamide was administered (120 mg/kg, i.p.) 15 min before STZ. The development of hyperglycemia was confirmed by the elevated blood glucose levels determined at fixed intervals, which was confirmed by measuring fasting blood glucose levels in rats' blood taken from the tail vein. Supplementation with ethanolic extract of K. pinnata root bark (EEKP) significantly reduced the elevated blood glucose in STZ-induced hyperglycemia in rats. EEKP significantly restored the biochemical and antioxidant defense system. On the final day of the protocol, the extract also reduced inflammatory cytokines in the blood serum.

The progression of type II diabetes (T2D) is characterized by a complex and highly variable loss of beta-cell mass, resulting in impaired insulin secretion. Many T2D drug discovery efforts aimed at discovering molecules that can protect or restore beta-cell mass and function have been developed using limited beta-cell lines and primary rodent/human pancreatic islets. Various high-throughput screening methods have been used in the context of drug discovery, including luciferase-based reporter assays, glucose-stimulated insulin secretion, and high-content screening. In this context, a cornerstone of small molecule discovery has been the use of immortalized rodent beta-cell lines. Although insightful, this usage has led to a more comprehensive understanding of rodent beta-cell proliferation pathways rather than their human counterparts. Advantages gained in enhanced physiological relevance are offered by three-dimensional (3D) primary islets and pseudoislets in contrast to monolayer cultures, but these approaches have been limited to use in low-throughput experiments. Emerging methods, such as high-throughput 3D islet imaging coupled with machine learning, aim to increase the feasibility of integrating 3D microtissue structures into high-throughput screening. This review explores the current methods used in high-throughput screening for small molecule modulators of beta-cell mass and function, a potentially pivotal strategy for diabetes drug discovery.

Nanotechnology is a captivating contemporary technology owing to its extensive range of potential applications. This study emphasizes nanomaterials, substances with a size <100 nm, offering better qualities than coarse particles. Nanoparticles have several advantages compared with conventional drug delivery methods, including enhanced bioavailability and a larger surface area because of their smaller particle size. These characteristics make the nanoparticles a viable clinical candidate. Controlled-release drug delivery systems and targeted drug delivery systems rely heavily on nanoparticles. Because traditional drug delivery methods fail to achieve targeted drug delivery, resulting in toxicity, low bioavailability, poor therapeutic outcomes, and so on, these drug nanoparticles excel in all these areas. Researchers are already interested in developing drug delivery systems such as niosomes, bilosomes, and dendrimers. Nanoemulsion is one of these technologies; nanoemulsions outperform traditional emulsions in terms of pharmacodynamics and pharmacokinetics. Nanoemulsion effectively surpasses the constraints of standard emulsions, primarily by offering enhanced bioavailability, reduced toxicity, improved absorption, and the potential to be used in targeted drug delivery or controlled-release drug delivery systems. This particular work explores several aspects of nanoemulsions, including their constituents, classification, techniques for preparation, criteria for assessment, commercial applications, and future prospects.

This study aimed to develop a nanoparticle drug delivery system using poly (lactic-co-glycolic acid) (PLGA) for enhancing the therapeutic efficacy of lurasidone hydrochloride (LH) in treatment of schizophrenia through intramuscular injection. LH-loaded PLGA nanoparticles (LH-PNPs) were prepared using the nanoprecipitation technique and their physicochemical characteristics were assessed. Particle size (PS), zeta potential, morphology, % encapsulation efficiency, % drug loading, drug content, and solid-state properties were analyzed. Stability, in vitro release, and in vivo pharmacokinetic studies were conducted to evaluate the therapeutic efficacy of the developed LH-PNPs. The optimized batch of LH-PNPs exhibited a narrow and uniform PS distribution before and after lyophilization, with sizes of 112.7 ± 1.8 nm and 115.0 ± 1.3 nm, respectively, and a low polydispersity index. The PNPs showed high drug entrapment efficiency, drug loading, and drug content uniformity. Solid-state characterization indicated good stability and compatibility, with a nonamorphous state. The drug release profile demonstrated sustained release behavior. Intramuscular administration of LH-PNPs in rats resulted in a significantly prolonged mean residence time compared with the drug suspension. These findings highlight that intramuscular delivery of the LH-PNP formulation is a promising approach for enhancing the therapeutic efficacy of LH in treatment of schizophrenia.

Glioblastoma, commonly known as glioblastoma multiforme (GBM), is one of the deadliest and most invasive types of brain cancer. Two factors account for the majority of the treatment limitations for GBM. First, the presence of the blood-brain barrier (BBB) renders malignancy treatment ineffective, leading to recurrence without full recovery. Second, several adverse effects are associated with the drugs used in conventional GBM treatment. Recent studies have developed nanocarrier systems, such as liposomes, polymeric micelles, dendrimers, nanosuspensions, nanoemulsions, nanostructured lipid carriers, solid lipid nanocarriers, metal particles, and silica nanoparticles, which allow drug-loaded formulations to penetrate the BBB more effectively. This has opened up new possibilities for overcoming therapy issues. Extensive and methodical searches of databases such as PubMed, Science Direct, Google Scholar, and others were conducted to gather relevant literature for this work, using precise keyword combinations such as "GBM," "brain tumor," and "nanocarriers." This review provides deep insights into the administration of drugs using nanocarriers for the management of GBM and explores new advancements in nanotechnology. It also highlights how scientific developments can be explained in connection with hopeful findings about the potential of nanocarriers for the future successful management of GBM.

A reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed to analyze the simultaneous estimation of doxorubicin and clotrimazole. The method was achieved by Nucleodur C18 column with dimension 250 × 4.6 mm (5 μm) using gradient elution. The mobile phase contained 0.2% formic acid (pH 3.2) and acetonitrile. The flow rate was kept at 1.0 mL/min and detection and quantitation of both drugs (doxorubicin and clotrimazole) were achieved using a photodiode array detector at 276 nm, which was the isosbestic point for both drugs. The proposed method was validated according to the current International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use guidelines for specificity, linearity, accuracy, precision, and robustness. The developed method showed a linear response (R² > 0.999), and was accurate (recoveries 97%-103%), precise (resolution ≤1.0%), sensitive, and specific. Thus, the developed RP-HPLC method for the simultaneous estimation of both drugs was successfully validated and can be utilized for the estimation of these drugs in the formulations being developed.

Antimalarial drugs are being encapsulated in nanotechnology-based carriers because there are not enough new treatment options and people are becoming more resistant to the ones that are already available. This approach uses two or more biochemical targets of malarial parasites. The codelivery of artemether and lumefantrine (AL) combines the synergistic effect of artemether for an early onset of action followed by the prolonged effect of lumefantrine. The bioavailability of artemether and lumefantrine is low due to their low solubility. Thus, an alternative lipidic formulation, namely nanocochleate, was developed for the selected drugs by adding calcium ions into preformed nanoliposomes (AL-loaded liposomes). Using phospholipon 90H and cholesterol, a thin-film hydration method produced drug-loaded liposomes. The synthesized AL-loaded liposomes were further incorporated into nanocochleates. The formulations were evaluated for in vitro and in vivo parameters. Nanocochleates had a particle size of 200.7 nm, a zeta potential of -9.4 mV, and an entrapment efficiency of 73.12% ± 1.82% and 61.46% ± 0.78%, respectively, for artemether and lumefantrine. Whereas liposomes had a particle size of 210 nm and an entrapment efficiency of 67.34% ± 1.52% and 53.24% ± 0.78%, respectively, for artemether and lumefantrine. An X-ray diffraction study confirmed the amorphous state of artemether and lumefantrine in liposomes and nanocochleate. Nanocochleate showed a controlled release profile for loaded drugs. When compared with free drugs, nanocochleate showed low tissue distribution and a 20-fold increase in bioavailability in rats. Thus, nanocochleate offers an interesting alternative to an existing dosage form for the treatment of malaria.

One of the most often utilized methods for drug discovery is molecular docking. With docking, one may discover new therapeutically relevant molecules by targeting the molecule and predicting the target-ligand interactions as well as different conformation of ligand at various positions. The prediction signifies the effectiveness of the molecule or the developed molecule having different affinity with target. Drug discovery plays an important role in the development of a new drug molecule of different moiety attached to it, which leads us in the management of several diseases. In silico approach led us to identification of numerous diseases caused by virus, fungi, bacteria, protozoa, and other microorganisms that affect human health. By means of computational approach, we can categorize disease symptoms and use the drugs available for such types of warning signs. After the docking process, molecular dynamics computational technique helps in the simulation of the physical movement of atoms and molecules for a fixed period of time, giving a view of the dynamic evaluation of the system. This review is an attempt to illustrate the role of molecular docking in drug development.