Microbubbles, gas-filled particles, are used in ultrasound-triggered drug and gene delivery. They are biocompatible, can be injected intravenously, and some are clinically approved. Ultrasound can destroy microbubbles, enabling targeted drug delivery and enhancing drug action. The ultrasound field can be focused on target tissues, improving treatment selectivity and reducing side effects. Microbubbles enhance ultrasound energy deposition in tissues and act as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection have been observed in areas where microbubbles and plasmid DNA are administered intravascularly. Clinical trials show that microbubbles can accelerate blood clot dissolution when used with thrombolytic agents. Microbubbles are small (1-8 µm) gas-filled microspheres. First-generation microbubbles, like Albunex, were filled with air but dissolved quickly. Second- and third-generation microbubbles use inert gases like perfluorocarbons, which have longer lifespans. Microbubbles have high acoustic backscatter, making them useful for ultrasound imaging, especially in echocardiography. Their acoustic backscatter depends on factors like gas compressibility, bubble size, and ultrasound frequency. Ligand-mediated targeting allows microbubbles to adhere to specific cellular epitopes and receptors, enhancing their use in drug delivery. Ligands like antibodies, carbohydrates, and peptides can be attached to microbubbles. Covalent or non-covalent binding strategies are used, with covalent bonds being more stable. Microbubbles can be targeted to various receptors, such as ICAM-1, VCAM-1, and selectins, improving their adhesion to activated endothelium. Ultrasound can enhance microbubble destruction, leading to bioeffects like hemolysis, microvascular leakages, and capillary ruptures. However, these effects can be therapeutic, such as in thrombolysis, where microbubbles enhance ultrasound's ability to dissolve clots. Microbubbles can also increase vascular permeability, allowing drugs and cells to enter tissues. They can enhance cell membrane permeability, enabling drug and gene delivery through sonoporation, which creates transient pores in cell membranes. Microbubbles can be used for gene delivery by enhancing transfection efficiency. They can be loaded with DNA or other genetic material and released upon ultrasound activation. Polymeric microbubbles offer higher loading capacity and can be designed to release drugs slowly. Microbubbles can also be combined with other drug delivery systems, such as liposomes or nanoparticles, to improve drug delivery. Microbubbles have significant clinical potential, especially in oncology and vascular applications. They can improve drug penetration into tissues, enhance drug delivery, and reduce side effects. Future research aims to optimize microbubble-based drug delivery systems for various therapeutic applications.Microbubbles, gas-filled particles, are used in ultrasound-triggered drug and gene delivery. They are biocompatible, can be injected intravenously, and some are clinically approved. Ultrasound can destroy microbubbles, enabling targeted drug delivery and enhancing drug action. The ultrasound field can be focused on target tissues, improving treatment selectivity and reducing side effects. Microbubbles enhance ultrasound energy deposition in tissues and act as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection have been observed in areas where microbubbles and plasmid DNA are administered intravascularly. Clinical trials show that microbubbles can accelerate blood clot dissolution when used with thrombolytic agents. Microbubbles are small (1-8 µm) gas-filled microspheres. First-generation microbubbles, like Albunex, were filled with air but dissolved quickly. Second- and third-generation microbubbles use inert gases like perfluorocarbons, which have longer lifespans. Microbubbles have high acoustic backscatter, making them useful for ultrasound imaging, especially in echocardiography. Their acoustic backscatter depends on factors like gas compressibility, bubble size, and ultrasound frequency. Ligand-mediated targeting allows microbubbles to adhere to specific cellular epitopes and receptors, enhancing their use in drug delivery. Ligands like antibodies, carbohydrates, and peptides can be attached to microbubbles. Covalent or non-covalent binding strategies are used, with covalent bonds being more stable. Microbubbles can be targeted to various receptors, such as ICAM-1, VCAM-1, and selectins, improving their adhesion to activated endothelium. Ultrasound can enhance microbubble destruction, leading to bioeffects like hemolysis, microvascular leakages, and capillary ruptures. However, these effects can be therapeutic, such as in thrombolysis, where microbubbles enhance ultrasound's ability to dissolve clots. Microbubbles can also increase vascular permeability, allowing drugs and cells to enter tissues. They can enhance cell membrane permeability, enabling drug and gene delivery through sonoporation, which creates transient pores in cell membranes. Microbubbles can be used for gene delivery by enhancing transfection efficiency. They can be loaded with DNA or other genetic material and released upon ultrasound activation. Polymeric microbubbles offer higher loading capacity and can be designed to release drugs slowly. Microbubbles can also be combined with other drug delivery systems, such as liposomes or nanoparticles, to improve drug delivery. Microbubbles have significant clinical potential, especially in oncology and vascular applications. They can improve drug penetration into tissues, enhance drug delivery, and reduce side effects. Future research aims to optimize microbubble-based drug delivery systems for various therapeutic applications.