Intravesical drug delivery approaches for improved therapy of urinary bladder diseases

Diseases of the urinary bladder have high incidence rates and burden healthcare costs. Their pharmacological treatment involves systemic and local drug administration. The latter is generally accomplished through instillation of liquid formulations and requires repeated or long-term catheterization that is associated with discomfort, inflammation and bacterial infections. Consequently, compliance issues and dropouts are frequently reported. Moreover, instilled drugs are progressively diluted as the urine volume increases and rapidly excreted. When penetration of drugs into the bladder wall is needed, the poor permeability of the urothelium has also to be accounted for. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. Particularly, indwelling delivery systems suited for i) insertion into the bladder through the urethra, ii) intra-organ retention and prolonged release for the desired time lapse, iii) final elimination, either spontaneous or by manual removal, have been proposed to reduce the number of catheterization procedures and reach higher drug levels at the target site. Vesical retention of such devices is allowed by the relevant expansion that can either be triggered from the outside or achieved exploiting elastic and purposely 4D printed shape memory materials. In this article, the main rationales and strategies for improved intravesical delivery are reviewed.