Neugeborenen- und Kindermedizin

Abstrakt

Drug Metabolism and Buffer Behaviour in Paediatrics in Relation to Birth Exposure

Alisha Sheikh

Although pediatric drug development has progressed over the past decades, off-label use of adult pediatric drugs remains a significant clinical problem. Nano-based drugs are important drug delivery systems that can improve the bioavailability of various therapeutics. However, the use of nanobased drugs for use in the pediatric population is challenged by the lack of pharmacokinetic (PK) data in this population. To fill this data gap, we examined the PK of polymer-based nanoparticles in term-equivalent neonatal rats. It is a polymeric nanoparticle that has been extensively studied in adult populations but less commonly used in neonates and children. We quantified the PK parameters and biodistribution of PLGA-PEG nanoparticles in period-equivalent healthy rats, demonstrating the PK and biodistribution of polymeric nanoparticles in neonatal rats. We further investigated the effects of surfactants used to stabilize PLGAPEG particles on PK and biodistribution. The nanoparticles showed the highest accumulation in serum 4 hours after intraperitoneal injection, 54.0% of the injected dose for particles containing Pluronic® F127 (F127) as a stabilizer and 54.0% for particles containing poloxamer 188 (P80) as a stabilizer. 54.6% of the dose. ) as a stabilizer. The half-life of PLGA-PEG particles loaded with F127 was 5.9 hours, which was significantly longer than the half-life of 1.7 hours for PLGA-PEG particles loaded with P80. Among all organs, liver showed the highest accumulation of nanoparticles. Twenty-four hours after dosing, the accumulation of PLGA-PEG particles in the F127 formulation was 26.2% of the injected dose, and the accumulation of particles in the P80 Less than 1% of injected nanoparticles were observed in healthy rat brains for F127 and P80 formulated particles. These PK data inform the application of polymeric nanoparticles in neonates and provide a basis for the transfer of polymeric nanoparticles for drug delivery in the pediatric population.