Mucoadhesive gellan gum-based and carboxymethyl cellulose -based hydrogels containing gemcitabine and papain for bladder cancer treatment.

Local treatment of bladder cancer faces several limitations such as short residence time or low permeation through urothelium tissue. The aim of this work was to develop patient-friendly mucoadhesive gel formulations combining gemcitabine and the enzyme papain for improved intravesical chemotherapy delivery. Hydrogels based on two different polysaccharides, gellan gum and sodium carboxymethylcellulose (CMC), were prepared with either native papain or papain nanoparticles (nanopapain) to explore for the first time their use as permeability enhancers through bladder tissue. Gel formulations were characterized regarding enzyme stability, rheological behavior, retention on bladder tissue and bioadhesion, drug release properties, permeation capacity, and biocompatibility. After 90 days of storage, the enzyme loaded in the CMC gels retained up to 83.5 ± 4.9 % of its activity in the absence of the drug, and up to 78.1 ± 5.3 with gemcitabine. The gels were mucoadhesive and the enzyme papain showed mucolytic action, which resulted in resistance against washing off from the urothelium and enhanced permeability of gemcitabine in the ex vivo tissue diffusion tests. Native papain shortened lag-time tissue penetration to 0.6 h and enhanced 2-fold drug permeability All formulations demonstrated pseudoplastic behavior and no irritability. Overall, the developed formulations have potential as an upgraded alternative to intravesical therapy for bladder cancer treatment.

Mucoadhesive Polymers and Their Applications in Drug Delivery Systems for the Treatment of Bladder Cancer.

Bladder cancer (BC) is the tenth most common type of cancer worldwide, affecting up to four times more men than women. Depending on the stage of the tumor, different therapy protocols are applied. Non-muscle-invasive cancer englobes around 70% of the cases and is usually treated using the transurethral resection of bladder tumor (TURBIT) followed by the instillation of chemotherapy or immunotherapy. However, due to bladder anatomy and physiology, current intravesical therapies present limitations concerning permeation and time of residence. Furthermore, they require several frequent catheter insertions with a reduced interval between doses, which is highly demotivating for the patient. This scenario has encouraged several pieces of research focusing on the development of drug delivery systems (DDS) to improve drug time residence, permeation capacity, and target release. In this review, the current situation of BC is described concerning the disease and available treatments, followed by a report on the main DDS developed in the past few years, focusing on those based on mucoadhesive polymers as a strategy. A brief review of methods to evaluate mucoadhesion properties is also presented; lastly, different polymers suitable for this application are discussed.