Left to right: Elliott Donaghue, Pakulska and Obermeyer. Credit: Marit Mitchell.
Left to right: Elliott Donaghue, Pakulska and Obermeyer. Credit: Marit Mitchell.

The sticky surface of nanoparticles can be used to deliver drugs, proteins, and other biomolecules without encapsulation, according to researchers from the Universities of Toronto and Oxford [Pakulska et al., Sci. Adv. 2 (2016) e1600519].

Loading polymer particles with therapeutic molecules is a popular strategy to mitigate the side effects of frequent administration of high-dose drugs. But while this approach can provide slow, controlled release of drugs and therapeutics inside the body, there are limitations. It is not easy to cram proteins and drug molecules into nanoparticles, so loads can be low, cargo can be lost from the carrier, and proteins can lose their activity.

Instead, Molly S. Shoichet and her colleagues have found that simple electrostatic interactions can effectively stick proteins onto the surface of nanoparticles made of poly(lactic-co-glycolic acid) (PGLA), which has a longstanding clinical track record thanks to its biocompatibility and biodegradability. The researchers adsorbed positively charged protein therapeutics onto the surface of negatively PGLA nanoparticles dispersed in a jelly-like hydrogel.

“In our system, the PLGA particles are negatively charged at neutral pH – because their carboxylic acids are deprotonated to carboxylate anions,” explains Shoichet.

Once inside the body, the nanoparticles start to degrade, diminishing their negative charge and weakening the electrostatic interactions with their protein cargo. The proteins are then gradually released into the body. 

“The exciting thing is that we don’t have to encapsulate proteins in order to control their release,” says Shoichet. “We can control release for several weeks simply through these electrostatic interactions.”

In fact, the release rate of the proteins can be controlled by varying the nanoparticle concentration, size, and local pH.

“The approach is very practical and significantly simpler than current approaches because the nanoparticles can be formulated separately and then simply mixed with proteins,” says Shoichet.

At the moment, approach is limited to positively charged proteins. To carry and delivery negatively charged proteins, a positively charged polymeric nanoparticle would have to be developed, says Shoichet. The researchers are already using the protein-delivery strategy in pre-clinical studies of diseases such as stroke and spinal cord injuries.

“The incorporation of the protein and nanoparticles in hydrogels allows us to achieve controlled, local and sustained release to the central nervous system using innovative strategies,” Shoichet says.

Omid C. Farokhzad of Brigham and Women’s Hospital, Harvard Medical School, believes thatthe technology may have applications in local delivery.

“The universality of this delivery system will be determined after exploring proteins with a myriad of physicochemical properties,” he adds. “So far, the authors have demonstrated proof-of-concept with three proteins, which is a terrific starting point.”

This article was originally published in Nano Today (2016), doi:10.1016/j.nantod.2016.06.002