Drug Loading in Poly(butyl cyanoacrylate)-Based Polymeric Microbubbles

Abstract

Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. In order to better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e. for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e. four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.

Theranostic Trigger‐Responsive Carbon Monoxide‐Generating Microbubbles

“…[ 2,44 ] The thicker shell of PBCA MB bears, therefore, a larger depot for drug “cargo”. [ 10,11,44 ]…”

“…[2,44] The thicker shell of PBCA MB bears, therefore, a larger depot for drug "cargo". [10,11,44] By encapsulation of CORM-1 in PBCA MB, the use of organic solvents as solubilizer could be avoided. MB were synthesized based on anionic emulsion polymerization in the presence of hydroxyl ions.…”

“…[5][6][7] On the one hand, especially in case of polymerbased MB, the shell can be very efficiently loaded with drug molecules. [8][9][10][11] On the other hand, the combination of MB with US gives rise to a number of mechanical and physical phenomena, such as stable or inertial cavitation, micro-streaming and jet formation, which induce "sonopermeation" of key biological barriers, and which thereby improve drug delivery to tumors and to the brain. [12][13][14][15][16][17] Carbon monoxide (CO) is a gaseous signaling molecule that modulates inflammation, cell survival, and recovery after myocardial infarction.…”

“…[33] This calls for formulation of CORM-1 in a drug delivery system suitable for transporting hydrophobic compounds, such as polymeric micelles and polymeric MB. [10,11] Here, to enable CORM-1 delivery and exploit the beneficial anti-inflammatory and cell-protective effects of CO, we developed CORM-1-containing MB (COMB). We loaded the prodrug in the shell of MB consisting of the biocompatible polymer poly-n-butyl-cyanoacrylate (PBCA), which allows for efficient encapsulation of the hydrophobic drug molecules.…”

“…[ 33 ] This calls for formulation of CORM‐1 in a drug delivery system suitable for transporting hydrophobic compounds, such as polymeric micelles and polymeric MB. [ 10,11 ]…”