Intravesical drug delivery approaches for improved therapy of urinary bladder diseases

Abstract

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.

Rac1 as a Target to Treat Dysfunctions and Cancer of the Bladder

“…The treatment of recurrent urinary tract infections usually relies on the use of intravenous antibiotic therapy (which can lead to complications due to allergy or drug-resistance). Repeated intravesical drug delivery is also possible, but it is more challenging [ 60 ]. The efficacy is these treatments is suboptimal at present.…”

Nontoxic Natural Polymeric Particle Vehicles Derived from Hyaluronic Acid and Mannitol as Mitomycin C Carriers for Bladder Cancer Treatment

“…Furthermore, micro/nanoparticles with mucoadhesive properties and a highly viscous nature provide prolonged residence time in the bladder and avoid repeated administration of toxic cancer drugs. Viscoelastic gel forms of the microgels could lead to a proper attachment to the bladder via mucoadhesive effects . It is very well known that bioadhesive features of the materials are dependent on the structure of the molecular network, the surface charge, the molecular weight of the polymer chain, chain flexibility, and hydrogen bonding capability of the groups, such as hydroxyl, carboxylic acid, amine, and so forth, delivering good distribution into the polymeric mucous chains.…”

Recent Advances in Antimicrobial Coatings and Material Modification Strategies for Preventing Urinary Catheter-Associated Complications

“…Catheters coated with drug-containing formulations act as drug delivery systems and are placed inside the bladder through the urethra to inhibit the bacterial infection inside. A few examples of devices which are used as drug delivery systems are: (1) the UROS infuser—it is a drug reservoir filled with a drug solution that has a pressure-responsive valve; (2) an intravesical balloon—it is inflated with drug formulations and is positioned inside the bladder; and (3) silicone tubes— they are prefilled with drug formulations [ 79 ]. Research has been carried out on antibiotic-coated urinary catheters for use over many years.…”