Researchers at the University of Alabama at Birmingham have developed cancer-fighting polymer capsules that they suggest could be used for targeted drug delivery of chemotherapeutics. The team’s work was published in ACS Nano.
The multi-layer capsules feature good imaging contrast, as well as efficient encapsulation of doxorubicin, according to the researchers. The vessels are triggered by low- and high-power doses of ultrasound to release their cargo.
“We envision an entirely different approach to treating solid human tumors of numerous pathologic subtypes, including common metastatic malignancies such as breast, melanoma, colon, prostate and lung, utilizing these capsules as a delivery platform,” lead researcher Eugenia Kharlampieva said in prepared remarks. “These capsules can protect encapsulated therapeutics from degradation or clearance prior to reaching the target and have ultrasound contrast as a means of visualizing the drug release. They can release their encapsulated drug cargo in specific locations via externally applied ultrasound exposure.”
The researchers used alternating layers of biocompatible tannic acid and poly(N-vinylpyrrolidone), which surround a core of solid silica or porous calcium carbonate. The core dissolves after the surrounding layers formed.
Varying the number of layers allowed the chemists to alter the physical characteristics of the capsules and consequently affect the vessel’s sensitivity to diagnostic ultrasound. One quarter of the empty microcapsules made with four layers of TA/low-molecular weight PVPON were triggered by 3 minutes of ultrasound. In comparison, capsules made with 15 layers of TA/low-molecular weight PVPON or 4 layers of TA/high-molecular weight PVPON did not rupture, according to the team.
Data showed that the ratio of capsule wall thickness to the diameter of the vessel is a key variable for sensitivity to rupture.
The team also tested the ultrasound imaging contrast of their microcarriers. They found that 5-micrometer-wide, empty vessels that were made with 8 layers of TA/low-molecular-weight PVPON had a ultrasound contrast comparable to the commercially available microsphere contrast agent, Definity.
When the team’s capsules, which have a shell thickness of 50 nanometers, were loaded with doxorubicin, the ultrasound imaging contrast increased 2- to 8-fold compared to empty capsules. The loaded vessels were highly stable, the team reported, with no change in imaging contrast after 6 months.
A therapeutic dose of ultrasound ruptured 50% of the 5-micrometer, doxorubicin-loaded vessels, which released enough chemotherapeutic to induce 97% cytotoxicity in human breast adenocarcinoma cells. Cells that were incubated with intact, loaded-vessels were still viable.
Kharlampieva said that the polymer capsules could eventually act as a diagnostic imaging agent and as a therapeutic drug-delivery carrier.
In their next preclinical experiment, the team plans to evaluate how long the capsules persist in blood circulation and where they distribute throughout the body in animal models.