Development and in vitro evaluation of tamoxifen and doxycycline loaded lipid-polymer hybrid nanoparticles for anticancer therapy

Lipid-polymer hybrid nanoparticles (LPHNPs) are innovative composite structures featuring a core-shell design, with a polymeric nanoparticle core surrounded by PEGylated lipid layers.This architecture combines liposome circulation with nanoparticle strength, offering a promising solution for multidrug-resistant cancers.The current study aimed to develop an integrated platform that leverages these advantageous characteristics.To achieve this, Tamoxifen-loaded nanoparticles were formulated using emulsion solvent evaporation technique with PLGA poly (lactic-co-glycolic) acid polymer, while Doxycycline-containing liposomes were developed through a film hydration method.These two components were then combined to fabricate LPHNPs.A range of physicochemical and structural analyses, including dynamic light scattering (DLS), laser diffraction analysis (LDA), and scanning electron microscopy (SEM), were performed.Cellular cytotoxicity was quantitatively assessed using the MTT assay, and biocompatibility was evaluated through in vivo acute toxicity tests on female albino mice.The average hydrodynamic sizes of Tamoxifen and Doxycycline formulations were 198.80 2.10 nm and 100.5 1.29 nm, respectively.After coating Tamoxifen nanoparticles with Doxycycline liposomes, resultant LPHNPs exhibited a diameter of 200.4 2.51 nm and a zeta potential of 4.45 2.51 mV.Notably, LPHNPs demonstrated a significant increase in cytotoxicity (p < 0.001) and showed reduced in vivo toxicity compared to free drugs, with no discernible toxicity observed in histopathology of vital organs, confirming their safety and efficacy.