<p>A stimuli-responsive nanogel composed of Chitosan, Pluronic F127 and PEG-dialdehyde was developed for controlled delivery of Bleomycin to treat superficial lymphatic malformations. We report the in vitro preclinical evaluation of a dual-stimuli-responsive nanogel platform for localized Bleomycin delivery. The formulated BLM@CS-PF127-PEGDA nanogels exhibited uniform particle size, positive surface charge and high encapsulation efficiency, confirming stable network formation. Morphological and thermal analyses indicated effective crosslinking and drug entrapment. They exhibited pH- and temperature-dependent release in vitro and enabling sustained drug availability under pathological conditions, along with injectability at room temperature and accelerated release under mildly acidic microenvironmental conditions. Cytocompatibility assays on HDLECs confirmed minimal carrier toxicity, while gene expression results indicated greater apoptotic activity and reduced inflammation compared with free Bleomycin. The formulation also inhibited endothelial migration, highlighting its potential to control abnormal lymphatic proliferation. The synthesized nanogel presents a promising and safer platform for effective sclerotherapy of lymphatic malformations through controlled and localized drug delivery.</p> Graphical Abstract <p></p>