Nanobubbles: A Novel Targeted Drug Delivery System

Abstract

Nanobubbles are nanometer size bubbles having different constituents of varying physicochemical characteristic for the inner core and outer shell. Nanobubbles are mainly fabricated to improve the stability, bioavailability and improve the biodistribution of the delivered drug to the specific targeted site. Their small sizes bubbles allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. Nanobubbles are developing as important contrast agents for imaging and carriers for drug delivery at targeted region. Sonication is the primary method for preparation of nanobubbles followed by thin-layer evaporation, high shear emulsification, mechanical agitation and coacervation or coalescence. With exposure to ultrasound/extracorporeal shock waves, the drug is liberated from the nanobubbles into the target cells. This review paper is an effort to reveal the different formulation development techniques briefly and varying shell and core content for developing nanobubbles.

Nanobubble technologies: Applications in therapy from molecular to cellular level

“…Nanobubbles with a shell are often referred to as armored nanobubbles. Shells are introduced to increase nanobubble stability by decreasing the interfacial tension and limiting the pressure difference between the gas and the solution (Pasupathy et al, 2022). The shell is classified as either hard or soft, with hard shells being more stable.…”

“…The shell is classified as either hard or soft, with hard shells being more stable. Shells can consist of lipids, phospholipids, proteins, polymers, and surfactants (de Leon et al, 2018;Khan et al, 2018a;Pasupathy et al, 2022). Other stability providing factors include the presence of a negative charge on the surface, hydrogen bonding between the bubble and solution, and contaminants at the gas-liquid interface (Ohgaki et al, 2010).…”

“…The type of gas has to be carefully considered for the intended purpose (Paknahad et al, 2021). The gas cores generally consist of hydrophobic and inert gases with poor solubility, significantly reducing the dissolution rate (Pasupathy et al, 2022). Gases that have been used in nanobubbles for biomedical applications include oxygen (Fig.…”

Construction of a Tumor-Targeting Nanobubble with Multiple Scattering Interfaces and its Enhancement of Ultrasound Imaging

“…[1][2][3][4] NB backbone-based nanotechnologies are focusing on their fabrication as an ideal tool due to their capacity for passive targeting via the enhanced permeability and retention (EPR) effect 5,6 and active targeting by functionalizing specific targeting ligands on the surfaces of NBs while transporting and controlling drug or gene delivery, thereby offering therapeutic potential. [7][8][9][10] However, when applied as ultrasound contrast agents (UCA), NBs commonly exhibit lower contrast signals compared to microbubbles due to the reduced scattering cross-section of a single bubble. 2,11,12 Efforts towards increasing the echogenicity of NBs have also been made in several studies, such as introducing a phase-change gas as the core of NBs when the NBs expand into more echogenic microbubbles under certain conditions, [13][14][15][16] or building a rattle-type mesoporous silica nanostructure with two contributing interfaces.…”

From Nanovesicles to Nanobubbles Based on Repeated Compression Method

“…In particular, shelled nanobubbles are receiving increasing attention in biomedical applications because of their stability and long lifetime for enhancing drug delivery and contrast ability in ultrasound imaging [ − ]. Interestingly, compared to microbubbles, nanobubbles are able to leave the vasculature and extravasate from blood vessels into surrounding tissues, thus improving delivery efficiency and localization [].…”