Pre-clinical investigation of the modulation of quetiapine plasma pharmacokinetics and tissues biodistribution by lipid-core nanocapsules

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Abstract

This study aims to investigate the changes in plasma pharmacokinetics and liver and brain distribution of quetiapine (QTP) due to its encapsulation into a polymeric nanocarrier. For this reason a bioanalytical method was developed and validated in order to quantify QTP in plasma, liver and brain tissue samples. The method was linear over the concentration range of 0.025–3.0 μg.mL (r2 > 0.98), accurate, precise (R.S.D < ± 15%) and the recoveries, stability and validation parameters are within the acceptable limits determined by international guidelines. Plasma pharmacokinetics, cerebral and hepatic distribution of the drug were carried out after intravenous administration of 5 mg kg−1 of nanoencapsulated (QLNC) or free-QTP to male Wistar rats. Increasing half-life was observed for QLNC in relation to free-QTP due to o significant decrease in total clearance. QTP volume of distribution was not altered due to encapsulation. An increase in QTP liver exposure was observed after nanoencapsulation probably due to a reduction in drug metabolization process.

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