I had the same question about ammo when arthritis in my hands steadily forced me downgrade caliber sizes over years. I ended up with 22 in an M&P 22 Compact. I am a dilgent researcher. Explored that option for weeks before acting. I started a long thread on the topic in the concealed carry forum.

My decision was to use CCI Mini Mag HP. It was one of the very few 22 rounds that expanded in gel out of 3.5 inch barrel. You can see that test at brasscatcher.com. Continuing research led me to really check out CCI Velocitor. I found good reason to use it. It expands but takes in more of wad cutter shape than a mushroom shape. There is a high likely hood it would tumble after penetrating. It can penetrate up to 13 inches in gel.

With the 22 for self defense the key is accuracy and penetration and Velocitor will give you penetration. Accuracy is a variable depending ob gun and shooter.

I had not gone to 380 because the pocket pistols were blowback and because of the weakness in my hands I had real problems racking them. Recently I learned of the Remington 380 being a locked breech design that is the easiest pocket pistol to rack. I tried it at my LGS and then rented it to try at the range. It was perfect. Great all metal, made in USA pistol with almost no recoil, and I can rack it with finger and thumb alone. Now I carry it daily.