Chemists at Université Laval have combined a common protein found in cow and sheep milk with mesoporous silica to create a new type of functionalized nanoparticle that can deliver drugs to specific regions of the body based on differences in pH. The technology could even be made capable of distinguishing cancer cells from healthy cells.
The mesoporous silica particles are about 150 nanometres in diameter. During their formation, surfactant micelles are used to create pores that range in size from 2-5 nanometres. “It’s like a very small sponge,”says Freddy Kleitz, an associate professor of chemistry at Laval. Those pores can be impregnated with drug molecules. Next, the outside of the particle is coated with β-lactoglobulin, the main component of whey protein in cow and sheep milk. By modifying the β-lactoglobulin with succinyl groups, the team, which recently published the work in Angewandte Chemie, was able to adjust the pH-sensitive nature of the protein. “Under low pH conditions, it polymerizes around the particle and clogs the pores,” says Kleitz. “At higher pH, the gel disassembles and the pores are opened.”
Tests with simulated gastric fluids showed that such particles would remain closed in the stomach, which has a pH of between one and two, but would release their drugs in the intestine, which has a pH of more than five. Kleitz believes that with further chemical modifications, particles could be adapted for more sophisticated drug delivery. “There is a pH difference between healthy cells and cancerous ones,” he says.“If you had something that is highly sensitive to small variations, you could enhance targeting and reduce side effects.”
Since silica is relatively inert and β-lactoglobulin comes from milk, biocompatibility should be high, and indeed cytotoxicity tests conducted by the team showed no effect. Kleitz is working with collaborators, including the Quebec city-based company Biovelia, toward commercialization. “β-lactoglobulin and mesoporous silica have been proposed before in drug delivery systems, but separately,” he says. “The combination is a new idea, and we’ve shown it works.”