Sustained Release of Doxorubicin through Semi-Interpenetrating Polymer Network-Stabilized Micelles

Developing effective drug delivery systems plays an important role in improving the therapeutic outcomes of anticancer agents. In this study, we investigated the potential of a micellar delivery system modified with semi-interpenetrating polymer networks (sIPN) to enhance the therapeutic efficacy of doxorubicin (Dox), a widely used chemotherapeutic agent. The sIPN-modified micelles were prepared by loading polymerizable tetraacrylate moiety into the core of sodium dodecyl benzene sulfonate (SDBS) micelles. To evaluate the stability of SDBS-micelle and SDBS-sIPN, we assessed the stability of the micellar structure under critical micelle temperature conditions. The results demonstrated that incorporating sIPN significantly enhanced the structural stability of the micelles, particularly in response to acrylate unit concentrations, leading to the 60 days continuous release of Dox. Furthermore, we examined the ability of SDBS-micelle-Dox and SDBS-sIPN-Dox to induce apoptosis and necrosis in HeLa cells. Annexin V/PI double staining and flow cytometry analysis revealed that SDBS-sIPN-Dox exhibited a sustained release profile of Dox, resulting in a reduced apoptotic response compared to free Dox and SDBS-micelle-Dox in the given time. These findings highlight the potential of the sIPN-modified micellar delivery system as an efficient drug delivery platform, enabling sustained release and minimizing adverse side effects associated with immediate drug release. The sustained release profile achieved through incorporation of sIPN structures holds great promise for improving the therapeutic outcomes of anticancer agents. Graphical Abstract This study involved the fabrication of semi-interpenetrating polymer network (sIPN)-stabilized micelles using an FDAapproved surfactant and loading anti-cancer drug inside. The stability of the resulting stabilized micelle and the prolonged release of the drug, doxorubicin, were evaluated. The findings underscore the potential of sIPN-stabilized micelles as an effective drug delivery platform, capable of providing sustained release and improving therapeutic outcomes for anticancer drugs.