LAUSR

Abstract Aim The study aimed to enhance phloretin’s oral absorption and systemic availability through nanoencapsulation within biodegradable polymers, improving its anti-oxidant and cardioprotective potential. Methods Phloretin-loaded polymeric nanocomposites were prepared using ionic gelation and optimised for yield, encapsulation, loading, particle size, PdI and zeta potential. The formulation was characterised by FTIR, XRD, FESEM and MS. In-vitro drug release, stability, pharmacokinetics, biodistribution, anti-oxidant capacity, haemolysis and both in-vitro and in-vivo assessments were conducted in an ischaemia-induced rat model. Results The average particle size, zeta potential, encapsulation and drug loading of the optimised nanoparticles were 105.8 ± 1.92 nm, −41.5 ± 1.10 mV, 92.36 ± 0.01% and 18.47 ± 0.38%, respectively. Nano-phloretin enhanced oral bioavailability, anti-oxidant capacity. In-vivo, it reduced myocardial infarct size by ∼46% versus ∼13% for free phloretin, showing significant cardiomyocyte protection and ROS suppression. Conclusion The study demonstrates polymer-based nanoparticles as effective oral drug delivery systems capable of enhancing both systemic bioavailability and therapeutic efficacy of the encapsulated drug.