Search Results (7)

Recurrent urinary tract infection (rUTI) continues to pose a formidable clinical challenge, largely owing to the rapid clearance of therapeutic agents from the bladder caused by short intravesical residence time and periodic urinary voiding. Although intravesical drug delivery has emerged as a promising local therapeutic strategy, conventional liquid instillations and physically crosslinked hydrogels frequently fail to sustain structural integrity and prolonged drug release within the dynamically changing bladder microenvironment. Herein, we develop a photocrosslinkable, pH-responsive intravesical floating drug delivery system (iFDDS) for sustained antimicrobial delivery. This system is fabricated using diacrylated Pluronic F127 (F127DA) as the core network-building component. The covalently crosslinked F127DA network confers superior mechanical stability while preserving amphiphilic micellar domains that enable efficient loading of hydrophobic drugs. A tertiary amine-based pH-responsive crosslinker (CLMA) is further integrated into the hydrogel matrix, endowing iFDDS with enhanced swelling capacity under the mildly acidic microenvironment. Additionally, lyophilization-induced porous architecture reduces the apparent density of the iFDDS below that of urine, achieving stable flotation for over 48 h and effectively mitigating the risk of urinary tract obstruction. The optimized iFDDS exhibits favorable catheter deliverability, shear-thinning rheological behavior adaptable to dynamic fluid conditions, and excellent biocompatibility with bladder epithelial cells. Upon loading with rifampicin, the iFDDS demonstrates potent and sustained antibacterial efficacy against Escherichia coli. This study establishes a robust, environment-adaptive platform for intravesical therapy, offering a viable strategy to address the short residence time limitation of conventional formulations and improve the therapeutic management of rUTI. Full article

Urinary cancers present a severe clinical challenge due to high recurrence rates. Standard intravesical therapies suffer from limited efficacy because of the urinary tract’s robust physiological defenses, namely, the dynamic washout effect during voiding and highly restrictive urothelial barriers, such as the anti-adhesive glycosaminoglycan layer and intercellular tight junctions. This review aims to explore how biomimetic engineering can overcome these obstacles by transitioning drug delivery from passive carriers to active, nature-inspired systems. We conducted a comprehensive review of the recent literature focusing on biomimetic strategies for intravesical drug delivery and urinary cancer theranostics. The analyzed approaches are categorized into chemical biomimicry (such as adhesion and camouflage) and structural/functional biomimicry (including adaptive devices and microrobots). Biomimetic strategies significantly enhance targeted drug retention and tissue penetration. Chemical biomimicry, utilizing mussel-inspired catechol chemistry and cell membrane camouflage, effectively bypasses the urothelial anti-adhesive defenses and reduces the immune clearance. Structural and functional biomimicry, such as naturally derived carriers and actively propelled magnetic or biohybrid microrobots, enables the precise spatial localization and controlled payload release in dynamic fluid environments. Furthermore, lab-on-a-chip technologies and patient-derived organoids (PDOs) offer scalable platforms for screening cargo-specific efficacies and tailoring treatments, providing a crucial bridge to personalized precision medicine. Integrating nature-inspired designs with advanced nanotechnologies provides a highly promising pathway with which to overcome the mechanical and biological barriers of the urinary tract. These biomimetic innovations hold the potential to shift the therapeutic paradigm for urinary oncology, paving the way for more efficient, targeted, and personalized precision medicine. Full article

Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette–Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy’s role in BC management, ultimately improving patient outcomes. Full article

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, great research efforts have been spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science, and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro-scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers and indwelling macro-scale devices, which were evaluated for applicability in local therapy for bladder cancer in vivo. Full article

This paper focuses on recent advancements in the development of 4D printed drug delivery systems (DDSs) for the intravesical administration of drugs. By coupling the effectiveness of local treatments with major compliance and long-lasting performance, they would represent a promising innovation for the current treatment of bladder pathologies. Being based on a shape-memory pharmaceutical-grade polyvinyl alcohol (PVA), these DDSs are manufactured in a bulky shape, can be programmed to take on a collapsed one suitable for insertion into a catheter and re-expand inside the target organ, following exposure to biological fluids at body temperature, while releasing their content. The biocompatibility of prototypes made of PVAs of different molecular weight, either uncoated or coated with Eudragit^®-based formulations, was assessed by excluding relevant in vitro toxicity and inflammatory response using bladder cancer and human monocytic cell lines. Moreover, the feasibility of a novel configuration was preliminarily investigated, targeting the development of prototypes provided with inner reservoirs to be filled with different drug-containing formulations. Samples entailing two cavities, filled during the printing process, were successfully fabricated and showed, in simulated urine at body temperature, potential for controlled release, while maintaining the ability to recover about 70% of their original shape within 3 min. Full article

In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies. Full article

Urinary tract infections (UTIs) are among the most common bacterial infections. In an increasing number of cases, pathogen (multi-)resistance hampers durable treatment success via the standard therapies. On the functional level, the activity of urinary excreted antibiotics is compromized by the efficient tissue colonization mechanism of uropathogenic Escherichia coli (UPEC). Advanced drug delivery systems aim at exploiting a glycan-mediated targeting mechanism, similar to the UPEC invasion pathway, to increase bioavailability. This may be realized by conjugation of intravesically applied drugs or drug carriers to chosen plant lectins. Higher local drug concentrations in or nearby bacterial reservoirs may be gained, with higher chances for complete eradication. In this study, preliminary parameters to clarify the potential of this biorecognitive approach were evaluated. Glycan-triggered interaction cascades and uptake processes of several plant lectins with distinct carbohydrate specificities were characterized, and wheat germ agglutinin (WGA) could be identified as the most promising targeter for crossing the urothelial membrane barrier. In partially differentiated primary cells, intracellular accumulation sites were largely identical for GlcNAc- and Mannose-specific lectins. This indicates that WGA-mediated delivery may also enter host cells via the FimH-dependent uptake pathway. Full article