Homebrews typically are distributed as NPDRM free software. They are PKG installed in the internal HDD.
To load homebrews from ISO they need to be re-signed with retail keys and the application should use relative paths to find the resource files in the new path. Some non properly signed homebrews can run through the debug icon "★ app_home/PS3_GAME".
ISO format requires a backup manager to mount the content. So this format is not convenient for homebrews.
webMAN MOD allows mount and play extracted PSN content via the debug icon. The files should extracted to a subdirectory within GAMEI folder of an USB FAT32. The subdirectory should be named with the TitleID or ContentID of the homebrew.
ISO format can be used to install homebrew packages stored in
INSDIR, PKGDIR or PS3_EXTRA folders. Also the packages can be placed in the root directory of the ISO to allow their installation using Package Manager.