A key to the team's novel delivery method was finding vesicles that naturally attach to spermatozoa. Charged lipids, for example, were identified as capable of attaching to the randomly charged patches on sperm membranes. However, because charged vesicles could inadvertently attach to other surfaces, the team also experimented with other lipids, finding success with two uncharged lipids that each attach to sperm because of their structural similarities to hyaluronic acid, which is known to bind stongly to sperm.
But what do you do with a vesicle-laden sperm? First, check that the sperm isn't too upset about the new luggage. "You realize there's a possibility that you find a way to link these vesicles to the sperm, and then the sperm might be really angry and decide not to swim anymore, not to fertilize anymore. But that didn't happen. The sperm's behavior was minimally altered by the attached vesicles, and its swimming ability wasn't hindered," says co-author Kyle Vanderlick, Dean of the School of Engineering & Applied Science and Thomas E. Golden, Jr. Professor of Chemical & Environmental Engineering. In addition to Vanderlick, the researchers include engineering postdoc Nienke Geerts and School of Medicine scientists James McGrath, Jill Stronk, and Gabor Huszar.
Most important of all, the attached vesicles do not prevent a sperm from fertilizing an egg. Using eggs and sperm from mice, preliminary experiments showed that sperm carrying vesicles were no less successful at fertilization than unladen sperm. Furthermore, vesicles loaded with a phosphorescent cargo were observable within the egg after fertilization, showing that the vesicles had penetrated the egg's membrane along with the sperm.
The team's research, recently featured on the cover of Reproductive Biomedicine Online, has important applications for drug delivery. Using vesicles, the spermatozoa in the Yale team's research could deliver virtually any molecule that can be dissolved in water, with potential applications in fertility therapies and STD prevention and treatment.
Source: Yale University
