Collagen nanobubbles as efficient carriers for targeted controlled release of ibrutinib†

Abstract

Nanobubbles are designed to increase structural stability and enhance the distribution of the transported drug to the targeted site. They can efficiently penetrate the desired area from the bloodstream due to the small size of nanobubbles. In general, the structure of the bubbles contains a gas inside, surrounded by an outer polymeric shell. In this study, perfluoropentane was utilized as a gaseous core whereas collagen was used to form shells because of its biodegradability and excellent biocompatibility. The release studies of collagen nanobubbles prepared at several drug doses were carried out in a Franz cell using a dialysis membrane at different pH (5.5–7.4) and temperature (4.0–40.0 °C) ranges. In the release experiments with collagen nanobubbles, it was observed that approximately 70% of the drug was released within 6 days at pH 7.4 whereas the same releasing rate was achieved within only 24 h after exploding by ultrasound treatment. At the same time, a cytotoxicity study was carried out to demonstrate the effectiveness of the synthesized nanobubbles. With increasing drug loading concentration and ultrasound treatment, the cytotoxic activities of nanobubbles became similar to those of the free drug (ibrutinib). Furthermore, cell culture studies were performed to assess in vitro drug-releasing efficiencies of nanobubbles by using the HeLa cell line as a model of soft cancer tissue. In conclusion, these nanobubbles could be classified as an efficient alternative to carrying active agents for treating soft tissue tumors.