Mechanisms and strategies to enhance penetration during intravesical drug therapy for bladder cancer

Bladder cancer (BCa) is one of the most prevalent cancers worldwide. The effectiveness of intravesical therapy for bladder cancer, however, is limited due to the short dwell time and the presence of permeation barriers. Considering the histopathological features of BCa, the permeation barriers for drugs to transport across consist of a mucus layer and a nether tumor physiological barrier. Mucoadhesive delivery systems or mucus-penetrating delivery systems are developed to enhance their retention in or penetration across the mucus layer, but delivery systems that are capable of mucoadhesion-to-mucopenetration transition are more efficient to deliver drugs across the mucus layer. For the tumor physiological barrier, delivery systems mainly rely on four types of penetration mechanisms to cross it. This review summarizes the classical and latest approaches to intravesical drug delivery systems to penetrate BCa.