The goal of current research was to develop a new form of effective drug, curcumin-loaded solid lipid nanoparticles (Cur-SLNs) and test its efficacy in the treatment of lung cancer. Different batches of SLNs were prepared by the emulsification–ultrasonication method. For the optimization of formulation, each batch was evaluated for particle size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). The formulation components and process parameters largely affected the quality of SLNs. The SLNs obtained with particle size, 114.9 ± 1.36 nm; PI, 0.112 ± 0.005; ZP, −32.3 ± 0.30 mV; EE, 69.74 ± 2.03%, and DL, 0.81 ± 0.04% was designated as an optimized formulation. The formulation was freeze-dried to remove excess water to improve the physical stability. Freeze-dried Cur-SLNs showed 99.32% of drug release and demonstrated a burst effect trailed by sustained release up to 120 h periods. The erythrocyte toxicity study of Cur-SLNs and its components demonstrated moderate hemolytic potential towards red blood cells (RBCs). The cytotoxic potential of the formulation and plain curcumin was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against A549 cell line. After 48 h of incubation, Cur-SLNs demonstrated more cytotoxicity (IC50 = 26.12 ± 1.24 µM) than plain curcumin (IC50 = 35.12 ± 2.33 µM). Moreover, the cellular uptake of curcumin was found to be significantly higher from Cur-SLNs (682.08 ± 6.33 ng/µg) compared to plain curcumin (162.4 ± 4.2 ng/µg). Additionally, the optimized formulation was found to be stable over the period of 90 days of storage. Hence, curcumin-loaded SLNs can be prepared using the proposed cost effective method, and can be utilized as an effective drug delivery system for the treatment of lung cancer, provided in vivo studies warrant a similar outcome.
Pyrazolines are a significant class of heterocyclic compounds with essential biological activities. They are quite stable, which has inspired medicinal chemists to experiment with the ring’s structure in many different ways to create a variety of pharmacological activities. The structures of numerous commercially available therapeutic agents contain a pyrazoline ring. Pyrazolines are well-known for their ability to treat neurodegenerative diseases. The neurodegenerative diseases that affect huge populations globally include Alzheimer’s disease (AD), Parkinson’s disease (PD), and psychiatric disorders. The neuroprotective properties of pyrazolines published since 2003 are covered in the current review. Structure–activity relationships (SARs), molecular docking simulation, anticholinesterase (anti-AChE), and monoamine oxidase (MAO A/B) inhibitory actions are all covered in this article. Pyrazolines were discovered to have beneficial effects in the management of AD and were revealed to be inhibitors of acetylcholine esterase (AChE) and beta-amyloid (Aβ) plaques. They were discovered to be efficient against PD and also targeted MAO B and COMT. It was discovered that the pyrazolines block MAO A to treat psychiatric diseases. Pyrazolines are significant heteroaromatic scaffolds with a variety of biological functions. They were discovered to be remarkably stable and serve as an indispensable anchor for the development of new drugs. By blocking AChE and MAOs, they may be used to treat neurodegenerative diseases. The discussion outlined here is an essential and helpful resource for medicinal chemists who are investigating and applying pyrazolines in neurodegenerative research initiatives as well as to expedite future research programs on neurodegenerative disorders.
For many years, Aegle marmelos (A. marmelos) has been used medicinally and as a dietary supplement. Despite this, there are minimal research data on A. marmelos phytochemical properties and pharmacological effects. This study aimed to explore the phytoconstituents, cytotoxicity, glucose uptake, and antioxidant and antidiabetic potential of an alcoholic extract of A. marmelos leaf. The cytotoxicity of A. marmelos in HepG2 cells was tested in vitro, and the results revealed that it has strong cytocompatibility and cytoprotective properties. The extract’s antioxidant activities were investigated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. Antioxidant potential was shown to be quite impressive. The enzymes α-amylase and α-glycosidase were found to be substantially inhibited by A. marmelos, with IC50 values of 46.21 and 42.07 mg/mL, respectively. In HepG2 cells, A. marmelos significantly reduced ROS levels that were elevated due to high glucose and enhanced glucose consumption (p < 0.05). These activities might be due to the enrichment of bioactive phytoconstituents analyzed chromatographically using GC/MS and HPLC. The findings of this study show that A. marmelos could be an effective restorative therapy for diabetes and related diseases.
A wound refers to a cut or blow that may result in primary or secondary infection or even death, if untreated. In the current study, we have explored the wound-healing properties of lidocaine nanogel, owing to its antioxidant and neutrophilic modulatory potential. Initially, the pre-formulation study was performed and then using central composite design (CCD) fabrication and the characterization of lidocaine-loaded nanoemulsion was carried out. After the preparation of a nanogel of lidocaine-loaded nanoemulsion, it was evaluated on various parameters, such as pH, spreadability, extrudability, drug content, in vitro drug release, dermatokinetic study and in vivo skin safety. Based on the pre-formulation study, the maximum solubility of lidocaine was found in oleic acid (324.41 ± 4.19 mg/mL) and in Tween 20 (192.05 ± 8.25 mg/mL), selected as a suitable emulsifier. The refractive index of the optimized nanoemulsion was found to be 1.35 ± 0.04, the electrokinetic potential was recorded as −15.47 ± 0.95 mV. The pH, spreadability and extrudability of nanogel was found to be 6.87 ± 0.51, 73.32 ± 4.59 gm.cm/sec and 107.41 ± 6.42 gm/cm2, respectively. The percentage of the cumulative drug content and drug release from nanogel was found to be 99.94 ± 1.70% and 93.00 ± 4.67%, respectively. Moreover, dermatokinetic study showed significantly (p < 0.0005) improved drug deposition and the in vivo skin safety study showed no sign of dermal erythematous lesion or any visible damage. Stability studies also testified the secureness of nanogel after storage in a prescribed environmental condition. Thus, this study provides substantial evidence for healing wounds effectively and the further evaluation of the in vivo model. The patent related to this work was published in the Indian Official Journal of the Patent Office (Issue number: 20/2022).
Currently, there are limited treatment options available for the monkeypox disease. We used a computational strategy to design a specific antigenic vaccine against pathogens. After using various immunoinformatic tools and filters, cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon gamma (IFN-γ)-inducing epitopes, which comprised the vaccine, in addition to other parameters, such as antigenic and allergic profiles, were assessed to confirm the safety of the vaccine. However, vaccine interaction and stability with Toll-like receptors (TLRs) were assessed by dynamic simulation methods, and it was found that the constructed vaccine was stable. In addition, C-IMMSIM tools were used to determine the immune-response-triggering capabilities of the vaccine. These immunoinformatic findings reveal that constructed vaccine candidates may be capable of triggering an efficient immune response for monkeypox viral infections. However, experimental evaluation is required to verify the safety and immunogenic profile of constructed vaccines.
There has been no assessment of the greenness of the described analytical techniques for the simultaneous determination (SMD) of caffeine and paracetamol. As a result, in comparison to the greener normal-phase high-performance thin-layer chromatography (HPTLC) technique, this research was conducted to develop a rapid, sensitive, and greener reversed-phase HPTLC approach for the SMD of caffeine and paracetamol in commercial formulations. The greenness of both techniques was calculated using the AGREE method. For the SMD of caffeine and paracetamol, the greener normal-phase and reversed-phase HPTLC methods were linear in the 50–500 ng/band and 25–800 ng/band ranges, respectively. For the SMD of caffeine and paracetamol, the greener reversed-phase HPTLC approach was more sensitive, accurate, precise, and robust than the greener normal-phase HPTLC technique. For the SMD of caffeine paracetamol in commercial PANEXT and SAFEXT tablets, the greener reversed-phase HPTLC technique was superior to the greener normal-phase HPTLC approach. The AGREE scores for the greener normal-phase and reversed-phase HPTLC approaches were estimated as 0.81 and 0.83, respectively, indicated excellent greenness profiles for both analytical approaches. The greener reversed-phase HPTLC approach is judged superior to the greener normal-phase HPTLC approach based on numerous validation parameters and pharmaceutical assays.