Microbubbles are widely used as ultrasound contrast agents owing to their excellent echoing characteristics under ultrasound radiation. However, their short sonographic duration and wide size distribution still hinder their application. Herein, we present a hard-template approach to produce perfluoropropane-loaded cerasomal microbubbles (PLCMs) with uniform size and long sonographic duration. The preparation of PLCMs includes deposition of Si-lipids onto functionalized CaCO3 microspheres, removal of their CaCO3 cores and mild infusion of perfluoropropane. In vitro and in vivo experiments showed that PLCMs had excellent echoing characteristics under different ultrasound conditions. More importantly, PLCMs could be imaged for much longer than SonoVue (commercially used microbubbles) under the same ultrasound parameters and concentrations. Our results demonstrated that PLCMs have great potential for use as a novel contrast agent in ultrasound imaging.

•A novel cerasomal microcapsule (CM) which combines the advantages of cerasome in colloidal high stability and microcapsule in size homogeneity was successfully developed to encapsulate anticancer drug doxorubicin.•The CM exhibited excellent biocompatibility and could encapsulate doxorubicin at high drug loading content (21.86 ± 1.08%).•The DOX loading cerasomal microcapsule (DLCM) showed a pH-sensitive drug release profile which can be well simulated using mathematical modeling.Efforts to improve the stability of liposomes have recently led to the development of organic–inorganic liposomal cerasomes. However, the uncontrollable size of cerasomes has greatly limited their biomedical applications. In this study, a novel strategy was introduced to fabricate hybrid liposomal cerasomes with high stability and uniform size. The hybrid lipids were first deposited onto CaCO3 microspheres through electrostatic interactions and self-assembly, and then the CaCO3 core was removed to obtain hollow microcapsules, i.e. the cerasomes. The species of the lipid oligomers was detected by MALDI-TOF-MS, which demonstrates the existence of siloxane network on microcapsules’ surface. Anticancer drug doxorubicin hydrochloride (DOX) loaded cerasomal microcapsule (DLCM) exhibited an initial burst release behavior followed by the sustained release and remarkably high stability towards surfactant solubilization and long term storage. The DLCM displayed a pH-dependent and sustained DOX release profile in vitro, which can be well explained using a well established mathematical model. Our results indicate that these novel cerasomal microcapsules have great potential to be applied as drug delivery system in cancer therapy.A biocompatible cerasomal microcapsule with high colloidal stability and uniform size was successfully developed to encapsulate anticancer drug doxorubicin at high drug loading content.