It'd be relatively easy to keep players in a decentralized bubble in each team's respective city. You'd basically just have to rent out a hotel campus for the entire season in each city, don't let anybody else stay there and have the hometown players and visiting teams live out of there for the entire season. You'd need to have a dedicated team plane/buses to transport them to practices, games, etc.
Continuously test the players, coaches and support staff, to include the pilots, bus drivers, hotel workers, etc.
You could even let a limited number of family members "live" with them in the hometown hotels to some extent if they agree to be tested continuously.
The players and the NFLPA would throw a hissy fit over it I'm sure because it would be very isolating/restrictive, and for that reason I think it's ultimately unrealistic, but it could be done if the appetite is there and to be honest, if you're being paid millions the appetite should be there.
I'd be more than happy to tell my wife, family and friends to fuck off for 5 months while I make anywhere from $1-20 million.