Ultrasound‐Triggered Delivery of Iproplatin from Microbubble‐Conjugated Liposomes

Abstract

The Pt IV prodrug iproplatin has been actively loaded into liposomes using a calcium acetate gradient, achieving a 3‐fold enhancement in drug concentration compared to passive loading strategies. A strain‐promoted cycloaddition reaction (azide‐ dibenzocyclooctyne) was used to attach iproplatin‐loaded liposomes L(Pt) to gas‐filled microbubbles (M), forming an ultrasound‐responsive drug delivery vehicle [M−L(Pt)]. Ultrasound‐triggered release of iproplatin from the microbubble‐liposome construct was evaluated in cellulo. Breast cancer (MCF‐7) cells treated with both free iproplatin and iproplatin‐loaded liposome−microbubbles [M−L(Pt)] demonstrated an increase in platinum concentration when exposed to ultrasound. No appreciable platinum uptake was observed in MCF‐7 cells following treatment with L(Pt) only or L(Pt)+ultrasound, suggesting that microbubble‐mediated ultrasonic release of platinum‐based drugs from liposomal carriers enables greater control over drug delivery.

Thrombin‐Loaded Magnetic Microbubbles for the Treatment of Pseudoaneurysms

“…If necessary, however, it would be possible to substitute an alternative coupling mechanism for the thrombin and magnetic particles, e.g., maleimide–thiol Michael addition or strain‐promoted [3+2] azide‐alkyne cycloaddition. [ 17,19 ]…”

“…If necessary, however, it would be possible to substitute an alternative coupling mechanism for the thrombin and magnetic particles, e.g., maleimide-thiol Michael addition or strainpromoted [3+2] azide-alkyne cycloaddition. [17,19] The absolute amount of thrombin on microbubbles was not directly measured. While the thrombin dose could potentially be inferred from the amount of thrombin that was not bound to the bubbles, this likely would not be acceptable for clinical translation of the microbubble formulation and an alternative quantification method would be required; although ultimately it is the activity of the attached thrombin that is the most clinically relevant parameter.…”

Microfluidic fabrication of monodisperse microcapsules with gas cores

“…Gas microcarriers refer to microstructures with gas cores, usually formed by embedding or encapsulating bubbles with sizes ranging from several micrometers to hundreds of micrometers within liposomes [1][2][3][4] or polymer microcapsules. [5][6][7][8] Encapsulated microbubbles can respond to external ultrasound 9,10 and are commonly used in biomedical fields such as drug delivery [11][12][13][14][15] and ultrasound contrast. [16][17][18][19][20][21][22] Above all, gas microbubbles that can act as endogenous gaseous biological messengers to mediate diverse physiological functions have therapeutic effects on tumors.…”

Fabrication and Evaluation of Ultrasound-Responsive Emulsion Loading Paclitaxel for Targeted Chemotherapy

“…More recently, drug-loaded carriers that were conjugated to the surface of microbubbles have been introduced. This enhanced the accumulation of drugs in the targeted site more effectively . Moreover, the drug carrier combined with a microbubble has the potential to prolong circulation time safely through the bloodstream, in contrast to a simple mixture with microbubbles, and to release the drug more effectively by ultrasound irradiation to the target area.…”