Optimized LC-MS/MS method for quantifying insulin degludec and liraglutide in rat plasma and Tissues: Application in pharmacokinetics and biodistribution.

We present an ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous detection of insulin degludec (I-Deg) and liraglutide (LIRA) in rat plasma and tissues, characterized by its sensitivity and selectivity. Chromatographic separation was achieved using an Acquity UPLC BEH C18 column, leveraging a mobile phase of acetonitrile and water (both with 0.1 % formic acid) under gradient elution over a run time of 7.5 min. The mass spectrometer operated in positive electrospray ionization multiple reaction monitoring (MRM) mode, tracking transitions of m/z 1221.6 â†’ 641.6 for I-Deg, m/z 938.7 â†’ 1064.1 for LIRA, and m/z 1184.7 â†’ 454.4 for the internal standard. Validation ranged from 5 to 100 ng/mL, exhibiting robust linearity (r2 > 0.99) and limits of detection (LOD) of 1.63-2.02 ng/mL for I-Deg and 0.96-1.62 ng/mL for LIRA. Limits of quantification (LOQ) were 2.38-4.76 ng/mL for I-Deg and 3.22-4.40 ng/mL for LIRA. Notably, no significant matrix effects were detected. Stability was confirmed under various conditions, and precision metrics (intraday RSD 1.68-8.05 % for I-Deg and 1.11-7.69 % for LIRA; interday RSD 1.39-8.61 % for I-Deg and 1.06-8.83 % for LIRA) alongside accuracy (90.5-114.9 % for I-Deg and 92.7-113.7 % for LIRA) were within acceptable ranges. The method was successfully applied to pharmacokinetic and biodistribution studies following simultaneous subcutaneous administration of LIRA and I-Deg in rats.

Mucoadhesive nanoemulsion enhances brain bioavailability of luteolin after intranasal administration and induces apoptosis to SH-SY5Y neuroblastoma cells.

Neuroblastoma is the most frequently diagnosed extracranial solid tumor in children and accounts for 7 % of all childhood malignancies and 15 % cancer mortality in children. Luteolin (LUT) is recognized by its anticancer activity against several types of cancer. The aim of this study was to prepare chitosan-coated nanoemulsion containing luteolin (NECh-LUT), investigate its potential for brain delivery following intranasal administration, and to evaluate its cytotoxicity against neuroblastoma cells. NECh-LUT was developed by cavitation process and characterized for its size, surface charge, encapsulation efficiency, and mucoadhesion. The developed formulation presented size 68 ± 1 nm, zeta potential + 13 ± 1 mV, and encapsulation efficiency of 85.5 ± 0.3 %. The NECh-LUT presented nearly 6-fold higher permeation through the nasal mucosa ex vivo and prolonged LUT release up to 72 h in vitro, following Baker-Lonsdale kinetic model. The pharmacokinetic evaluation of NECh-LUT revealed a 10-fold increase in drug half-life and a 4.4 times enhancement in LUT biodistribution in brain tissue after intranasal administration of single-dose. In addition, NECh-LUT inhibited the growth of neuroblastoma cells after 24, 48 and 72 h in concentrations starting from 2 µM. The NECh-LUT developed for intranasal administration proved to be a promising alternative for brain delivery of LUT, and a viable option for the treatment of neuroblastoma.