An injectable, thermosensitive and multicompartment hydrogel for simultaneous encapsulation and independent release of a drug cocktail as an effective combination therapy platform

Combination chemotherapy is potent to combat diseases. Simultaneous and segregated delivery of multiple drugs in a single vehicle is essential to achieve this objective. In the present study, an injectable, thermosensitive and multicompartment hydrogel (MCH) was developed by the facile cooperative and incompatible assembly of PEGylated hydrocarbon nanoparticles with PEGylated fluorocarbon nanoparticles. The cooperative assembly behavior was investigated by fluorescence resonance energy transfer (FRET) technology, and the result demonstrated that the incompatible nanoparticle cores possibly accounted for the multicompartment formation in hydrogel. Paclitaxel and doxorubicin could be easily and separately integrated into the different compartments of MCH serving as a sustained drug cocktail formulation. In vitro drug release indicated drugs were liberated in a simultaneous but independent manner without any effect on each other. In vitro and in vivo antitumor activity indicated that peritumoral injection of drug cocktail encapsulated MCH formulation could well achieve the combination effect, which significantly improved the tumor growth inhibition efficiency as well as minimized the drug-associated side effects compared to intravenous injection of free drug cocktail. Furthermore, such a delivery device would allow precise adjustment of drug dosage to the desired effect, achieve spatial–temporal simultaneous and synchronized presence of combination drugs in the target tissue and obviate repeated drug administrations to improve patient compliance. The thermosensitive multicompartment hydrogel cocktail formulation holds great promise for simultaneous and segregated delivery of multiple bioactive agents for sustained combination therapy.