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.

The State of the Art of Theranostic Nanomaterials for Lung, Breast, and Prostate Cancers.

The synthesis and engineering of nanomaterials offer more robust systems for the treatment of cancer, with technologies that combine therapy with imaging diagnostic tools in the so-called nanotheranostics. Among the most studied systems, there are quantum dots, liposomes, polymeric nanoparticles, inorganic nanoparticles, magnetic nanoparticles, dendrimers, and gold nanoparticles. Most of the advantages of nanomaterials over the classic anticancer therapies come from their optimal size, which prevents the elimination by the kidneys and enhances their permeation in the tumor due to the abnormal blood vessels present in cancer tissues. Furthermore, the drug delivery and the contrast efficiency for imaging are enhanced, especially due to the increased surface area and the selective accumulation in the desired tissues. This property leads to the reduced drug dose necessary to exert the desired effect and for a longer action within the tumor. Finally, they are made so that there is no degradation into toxic byproducts and have a lower immune response triggering. In this article, we intend to review and discuss the state-of-the-art regarding the use of nanomaterials as therapeutic and diagnostic tools for lung, breast, and prostate cancer, as they are among the most prevalent worldwide.

Semi-Solid Pharmaceutical Formulations for the Delivery of Papain Nanoparticles.

Papain is a therapeutic enzyme with restricted applications due to associated allergenic reactions. Papain nanoparticles have shown to be safe for biomedical use, although a method for proper drug loading and release remains to be developed. Thus, the objective of this work was to develop and assess the stability of papain nanoparticles in a prototype semi-solid formulation suitable for dermatological or topical administrations. Papain nanoparticles of 7.0 ± 0.1 nm were synthesized and loaded into carboxymethylcellulose- and poly(vinyl alcohol)-based gels. The formulations were then assayed for preliminary stability, enzyme activity, cytotoxicity studies, and characterized according to their microstructures and protein distribution. The formulations were suitable for papain nanoparticle loading and provided a stable environment for the nanoparticles. The enzyme distribution along the gel matrix was homogeneous for all the formulations, and the proteolytic activity was preserved after the gel preparation. Both gels presented a slow release of the papain nanoparticles for four days. Cell viability assays revealed no potential cytotoxicity, and the presence of the nanoparticles did not alter the microstructure of the gel. The developed systems presented a potential for biomedical applications, either as drug delivery systems for papain nanoparticles and/or its complexes.

An Updated Review of Macro, Micro, and Nanostructured Hydrogels for Biomedical and Pharmaceutical Applications.

Hydrogels are materials with wide applications in several fields, including the biomedical and pharmaceutical industries. Their properties such as the capacity of absorbing great amounts of aqueous solutions without losing shape and mechanical properties, as well as loading drugs of different nature, including hydrophobic ones and biomolecules, give an idea of their versatility and promising demand. As they have been explored in a great number of studies for years, many routes of synthesis have been developed, especially for chemical/permanent hydrogels. In the same way, stimuli-responsive hydrogels, also known as intelligent materials, have been explored too, enhancing the regulation of properties such as targeting and drug release. By controlling the particle size, hydrogel on the micro- and nanoscale have been studied likewise and have increased, even more, the possibilities for applications of the so-called XXI century materials. In this paper, we aimed to produce an overview of the recent studies concerning methods of synthesis, biomedical, and pharmaceutical applications of macro-, micro, and nanogels.