A Quality by Design (QbD) driven gradient high performance liquid chromatography method development for the simultaneous estimation of dasatinib and nilotinib in lipid nanocarriers.

Tyrosine kinase inhibitors (TKIs) are effective as a targeted treatment for chronic myeloid leukemia (CML), which can selectively suppress BCR-ABL1 kinase activity. CML therapy with TKIs combination has been supported by in-vitro, in-vivo, and patient-based data where the nilotinib-dasatinib co-administration has exerted superior anticancer efficacy with greater cellular uptake, less resistance to chemotherapy, and no additive adverse events encountered. Therefore, it is essential to develop a suitable analytical method for the simultaneous estimation of these drugs in the developed novel lipid nanocarriers like liposomes. Design of Experiment (DoE) has been implemented as a tool of QbD to systematically investigate the relation between the HPLC method attributes and analytical responses, i.e., chromatographic detection, quantification, and peak properties for dasatinib and nilotinib. An Ishikawa diagram is constructed to delineate possible influencing variables to the analytical performances. Afterward, 4 factors 2 level full factorial design (FFD) was employed to model and identify the main effects and interaction effects between the factors selected after the initial risk assessment. The suggested design space for optimized chromatographic conditions by QbD analysis is linear within the selected range of drug concentrations, accurate and precise, sensitive, and robust according to the ICH guidelines. The optimal method is comprised of a 1 mL/min flow rate of mobile phase (ACN and 20 mM KH2PO4 of pH 7.00) in gradient mode at 25 °C column temperature for 20 µL sample injection volume and detection wavelength fixed at 297 nm. Most importantly, this novel HPLC method is simple and selective enough to evaluate dasatinib and nilotinib content in the lipid nanocarriers.

Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway.

Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP. Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated. The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives.

Exosomes are nanosized (size ~ 30-150 nm) natural vesicular structures released from cells by physiological processes or pathological circumstances. Exosomes are growing in popularity as a result of their many benefits over conventional nanovehicles, including their ability to escape homing in the liver or metabolic destruction and their lack of undesired accumulation before reaching their intended targets. Various therapeutic molecules, including nucleic acids, have been incorporated into exosomes by different techniques, many of which have shown satisfactory performance in various diseases. Surface-modified exosomes are a potentially effective strategy, and it increases the circulation time and produces the specific drug target vehicle. In this comprehensive review, we describe composition exosomes biogenesis and the role of exosomes in intercellular signaling and cell-cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research and discuss future perspectives. In addition to the current status of exosomes as a therapeutic carrier, the lacuna in the clinical development lifecycles along with the possible strategies to fill the lacuna have been addressed.

COVID-19 vaccine-associated myositis - a case report.

Myositis is one of the uncommon adverse events following COVID-19 vaccination, and its mechanism is still unclear. A strong clinical suspicion and further evaluation are important not only for early diagnosis and management but also for better understanding of the unprecedented effects of this novel vaccine. We present a case of myositis following the first dose of the ChAdOx1 nCoV-19 Corona Virus Vaccine, evidenced by serology and MRI.

Green nanofiber mat from HLM-PVA-Pectin (Hibiscus leaves mucilage-polyvinyl alcohol-pectin) polymeric blend using electrospinning technique as a novel material in wound-healing process.

The present work is focused on fabrication of novel nanofiber (NF) mat as wound-healing scaffold using blends of novel combination of Hibiscus rosa-sinensis leaves mucilage (HLM)-Polyvinyl alcohol (PVA)-Pectin, which was never reported previously. Different ratios of the polymeric blends were electrospun by setting different parameters to achieve best possible electrospun nanofiber mat which was later crosslinked by glutaraldehyde vapor. The optimized formulation of nanofiber mat was characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The crosslinked sample was evaluated for its efficacy in wound healing using Swiss albino mice model, where rapid healing of excised wound was observed with faster epithelization in test mice group than control mice within a period of 8 days. The hemolysis test with optimized crosslinked nanofiber mat CrNF(S7-CL) indicated it to be hemo-compatible. There were no traces of optimized CrNF(S7-CL) when placed under the skin hypodermis in test mice groups revealing its biodegradable nature. The degradation pattern of CrNF(S7-CL) in soil reflects its eco-friendly behavior. Thus, the prepared nanofiber grade CrNF(S7-CL) can be considered as a novel material for faster wound healing and can also be explored for other biomedical applications.