The Future of Intravesical Drug Delivery for Non-Muscle Invasive Bladder Cancer

Abstract

Despite being the fifth most common cancer in the United States, minimal progress has been made in the treatment of bladder cancer in over a decade. Intravesical instillation of Bacillus Calmette-Guerin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC) has been in use for over 30 years and remains the standard treatment in cases of intermediate and high risk disease. Despite the relative success of intravesical BCG, unmet needs in the treatment of NMIBC persist. These challenges include disease recurrence and progression even with treatment with BCG, as well as issues regarding its availability and patient tolerability. The inherent properties of the bladder pose the biggest obstacle to developing effective intravesical treatments for NMIBC. Current research is now focusing on methods to improve the delivery of intravesical therapies. The objective of this review is to discuss novel intravesical drug delivery systems and how they are addressing these challenges in the treatment of NMIBC.

Intravesical Chemotherapy and Chemohyperthermia in Non-Muscle-Invasive Bladder Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics

“…Thus, further studies are needed to achieve a more solid clinical evidence [72]. Moreover, the knowledge of pharmacodynamics after the intravesical drug administration is crucial to understand the drug diffusion through bladder tissue and improve the development of novel drug delivery technologies [73].…”

Bacillus Calmette–Guérin strain differences as the basis for immunotherapies against bladder cancer

“…68 These methods have had promising results in vitro, and animal studies and clinical trials are pending. 68 These methods have had promising results in vitro, and animal studies and clinical trials are pending.…”

“…Various methods have been developed in order to improve the efficacy of BCG through the application of basic science. 68 These methods have had promising results in vitro, and animal studies and clinical trials are pending. Recombinant BCG strains expressing interferon-a are also currently being researched.…”

A novel, safe, fast and efficient treatment for Her2‐positive and negative bladder cancer utilizing an EGF‐anthrax toxin chimera

“…normal cells, thereby presenting a great opportunity for treating tumors while minimizing effects on normal cells. Nevertheless, dilution of the bladder content by urine influx and elimination of therapeutics due to bladder voiding requires the use of targeted anticancer drugs against tumor cells …”

“…Nevertheless, dilution of the bladder content by urine influx and elimination of therapeutics due to bladder voiding requires the use of targeted anticancer drugs against tumor cells. 19 Since bladder cancer cells are known to upregulate epidermal growth factor (EGF) receptor (EGFR) expression, 20 we tested the use of an EGF-targeted bacterial toxin designed to bypass the limitations of other EGF/toxin-based approaches as an antibladder cancer agent: Since EGFR-targeting therapeutics require receptor endocytosis to be active, impaired EGFR uptake (e.g., by Her2/neu upregulation or the presence of mutations affecting EGFR internalization) are predicted to negatively impact their efficacy. [21][22][23] Importantly, to bypass such limitations we previously devised an approach relying on receptor microclustering to induce nanoparticle uptake by bladder tumor cells.…”