Objective: The goal of the current study was to investigate the possible use of solid lipid nanosuspension (SLNs) as a drug delivery method to boost doxorubicin (DOX) brain-targeting performance after intranasal (i. n.) administration.  Methods: 33 factorial design was applied for optimization by using lipid concentration, surfactant concentration, and High-speed homogenizer (HSH) stirring time as dependent variables, and their effect was observed on particles size, Polydispersity index (PDI), and entrapment efficiency.  Results: With the composition of Compritol® 888 ATO (4.6 % w/v), tween 80 (1.9 % w/v), and HSH stirring time, the optimized formula DOX-SLNs prepared (10 min). Particle size, PDI, zeta potential, entrapment efficiency, percent in vitro release were found to be 167.47±6.09 nm, 0.23±0.02, 24.1 mV, 75.3±2.79, and 89.35±3.27 percent in 24 h, respectively, for optimized formulation (V-O). No major changes in particle size, zeta potential, and entrapping efficiency were found in the stability studies at 4±2 °C (refrigerator) and 25±2 °C/60±5% RH up to 3 mo.  Conclusion: Following the non-invasive nose-to-brain drug delivery, which is a promising therapeutic strategy, the positive findings confirmed the current optimized DOX-loaded SLNs formulation.

A simple, sensitive, and selective LC-MS/MS method was developed and validated for the quantification of carbocisteine in human plasma. Rosiglitazone was used as the internal standard and heparin was used as the anticoagulant. The chromatographic separation was performed by using the Waters Symmetry Shield RP 8, 150 × 3.9 mm, 5 μ column at 40°C with a mobile phase consisting of a mixture of methanol and 0.5% formic acid solution in a 40:60 proportion. The flow rate was 500 μl/min along with a 5 μl injection volume. Protein precipitation was used as the extraction method. Mass spectrometric data were detected in positive ion mode. The MRM mode of the ions for carbocisteine was 180.0 > 89.0 and for rosiglitazone it was 238.1 > 135.1. The method was validated in the concentration curve range of 50.000 ng/mL to 6000.000 ng/mL. The retention times of carbocisteine and the internal standard rosiglitazone were approximately 2.20 and 3.01 min, respectively. The overall run time was 4.50 min. This method was found suitable to analyze human plasma samples for the application in pharmacokinetic and BA/BE studies.