Preparation of Novel Dendrimeric Hyperbranched Polymer-Gd₂O₃ Composites Loaded With Sphingosine Inhibitor-I/II

Functionalized dendrimeric nanoparticles (BH40-PEG-F127-FA) were synthesized to develop a targeted delivery platform for combined therapeutic and imaging applications. Structural confirmation through FT-IR, ¹H-NMR, ¹³C-NMR, and MALDI-TOF mass spectrometry verified the successful formation of the macromolecular architecture. The nanoparticles exhibited hydrodynamic sizes of 190-255 nm, while transmission electron microscopy revealed micellar structures ranging from 35 to 190 nm. The critical micelle concentration of the copolymer was determined as approximately 0.001 mg/mL. Thermal analyses demonstrated the stability of BH40-PEG and BH40-PEG-F127-FA. Gd₂O₃ and sphingosine kinase inhibitors (SKI-I/II) were incorporated using a supercritical CO₂ method, and structural integrity after loading was confirmed by FT-IR and x-ray diffraction. Drug-release studies performed in phosphate-buffered saline (pH 6.7, 37°C) indicated a sustained release over 192 h. Cytotoxicity assays on A549 lung cancer cells and Beas-2B healthy epithelial cells revealed selective antiproliferative activity, while confocal microscopy demonstrated treatment-induced morphological alterations. Overall, BH40-PEG-F127-FA nanoparticles show strong potential as biocompatible carriers for targeted therapy and multimodal imaging.