"Getting something into a Gram-negative bacterium isn’t easy. Though the sum total of its boundary layers is thinner than for a Gram-positive, the outer and inner membranes are separated by a no-man’s land known as the periplasmic space (which contains the thinner peptidoglycan wall). The arrangement makes the cell much less permeable, apart from small water channels. Antibiotics that can get into and kill Gram-negative bacteria are therefore often small molecules, around a hundredth the size of a typical protein."

https://www.lrb.co.uk/blog/2024/january/like-scotch-eggs