Glycan-targeted drug delivery for intravesical therapy: in the footsteps of uropathogenic bacteria

Abstract

The human urothelium belongs to the most efficient biobarriers, and represents a highly rewarding but challenging target for local drug administration. Inadequate urothelial bioavailability is a major obstacle for successful treatment of bladder cancer and other diseases, yet little research has addressed the development of advanced delivery concepts for the intravesical route. A prominent example of how to overcome the urothelial barrier by means of specific biorecognition is the efficient cytoinvasion of UPEC bacteria, mediated by the mannose-targeted lectin domain FimH. Similar mechanisms of non-bacterial origin may be exploited for enhancing drug uptake from the bladder cavity. This review covers the current status in the development of lectin-based delivery strategies for the urinary tract. Different concepts for preparing and optimizing carbohydrate-targeted delivery systems are presented, along with important design parameters, benefits and shortcomings. Bioconjugate- and nano-/microparticle-based systems are discussed in further detail with regard to their performance in preclinical testing.