Hybrid Polyester Self-Immolative Polymer Nanoparticles for Controlled Drug Release.

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Drug delivery systems face challenges in achieving specific drug release at target sites.
• Self-immolative polymers offer high sensitivity to stimuli for advanced delivery applications.
• Hybrid systems combining different polymer degradation rates can enable tunable drug release.

Purpose of the Study:

• To develop and characterize hybrid polymer particles for controlled, stimuli-responsive drug release.
• To investigate the dual release mechanism of drug from poly(ethyl glyoxylate) (PEtG) and poly(d,l-lactic acid) (PLA) domains.
• To evaluate the impact of stimuli-responsive end-caps on particle degradation and drug release kinetics.

Main Methods:

• Synthesis of hybrid particles with varying ratios of PEtG and PLA.
• Incorporation of UV-light and thiol-responsive end-caps.
• Assessment of particle degradation using dynamic light scattering.
• Quantification of drug (celecoxib) and dye (Nile red) release.
• In vitro toxicity assays of drug-loaded particles.

Main Results:

• Triggered hybrid particles showed partial degradation dependent on the PEtG:PLA ratio.
• Controlled release of Nile red and celecoxib was observed, influenced by triggering and polymer ratio.
• In vitro toxicity assays indicated stimulus-dependent effects and highlighted the need to optimize surfactants.

Conclusions:

• Hybrid PEtG/PLA particles demonstrate potential for tunable, stimuli-responsive drug delivery.
• The dual release mechanism allows for both rapid burst and sustained drug release.
• Further optimization, particularly regarding surfactants, is needed to minimize background toxicity.