Hybrid Polyester Self-Immolative Polymer Nanoparticles for Controlled Drug Release

[Image: see text] Delivery systems have been developed to address problematic properties of drugs, but the specific release of drugs at their targets is still a challenge. Polymers that depolymerize end-to-end in response to the cleavage of stimuli-responsive end-caps from their termini, commonly referred to as self-immolative polymers, offer high sensitivity to stimuli and have potential for the development of new high-performance delivery systems. In this work, we prepared hybrid particles composed of varying ratios of self-immolative poly(ethyl glyoxylate) (PEtG) and slowly degrading poly(d,l-lactic acid) (PLA). These systems were designed to provide a dual release mechanism consisting of a rapid burst release of drug from the PEtG domains and a slower release from the PLA domains. Using end-caps responsive to UV light and reducing thiols, it was found that triggered particles exhibited partial degradation, as indicated by a reduction in their dynamic light-scattering count rate that depended on the PEtG:PLA ratio. The particles were also shown to release the hydrophobic dye Nile red and the drug celecoxib in a manner that depended on triggering and the PEtG:PLA ratio. In vitro toxicity assays showed an effect of the stimuli on the toxicity of the celecoxib-loaded particles but also suggested it would be ideal to replace the sodium cholate surfactant that was used in the particle synthesis procedure in order to reduce the background toxicity of the delivery system. Overall, these hybrid systems show promise for tuning and controlling the release of drugs in response to stimuli.