Physiological Barriers Research Articles

A Reflective Thematic Analysis Into the Perceptions of Pregnant Radiographers Regarding the Usefulness of the PregiDose Mobile App to Enhance Fetal Dosimetry and Well-Being: Qualitative Exploration.

Pregnancy apps are widely used by pregnant women, who benefit from self-tracking features to support their health goals. Pregnant radiographers are considered a high-risk group of health workers practicing in ionizing radiation environments. Radiation exposure above threshold limits can cause harmful genetic effects on a fetus. Accordingly, pregnant radiographers are required to wear special fetal dosimeters, which provide real-time readings of radiation dose exposure to the fetus. Pregnant radiographers have the responsibility to self-track their fetal doses to ensure that the threshold limit of 1 mGy is not exceeded. The traditional method used to track doses includes a written log of doses in a notebook. Thus, PregiDose, a unique offering in the context of pregnancy apps, was developed to enhance fetal dose tracking and monitoring using technological methods. This study aims to describe the users' perceptions of the app's usefulness using PregiDose in a natural setting. The overarching framework adopted for the study was a design science research (DSR) methodology encompassing five steps, namely (1) problem awareness, (2) suggestion, (3) development, (4) evaluation, and (5) conclusion. This paper presents the evaluation step of DSR. DSR step 4 included a qualitative approach to explore users' perceptions regarding the app. Data were collected using a semistructured interview guide. Open-ended questions were guided by the app's core features, namely dose tracking, education, and wellness. In total, 17 pregnant radiographers in South Africa enrolled to use the app, 9 (53%) engaged with the app, and 4 (24%) agreed to participate in the feedback interviews. The data were collected from October 2023 to March 2024 and analyzed using a reflective thematic data analysis method. Three overarching themes emerged from the data, namely (1) usefulness of PregiDose, (2) barriers to PregiDose adoption and use, and (3) recommendations for the advancement of PregiDose. Users labeled the app's usefulness as positive and perceived it as a modern approach to traditional dose-tracking methods. They perceived the graph output of the dose-tracking feature to be useful for viewing their accumulative doses. They did not fully engage with the journaling feature, indicating that it was a personal preference and not a practice they would usually engage in. Physiological barriers, such as fatigue and "pregnancy brain," were contributors to decreased engagement. Finally, because of the demanding workload and fast-paced nature of the radiography department, users recommended the automation of fetal dosimetry through the Internet of Things. PregiDose is an occupational health and safety mobile app developed for pregnant radiographers through a DSR approach. The app offers a modern method of dose tracking consistent with technological advancements in the context of self-tracking. However, future implementation would require using Internet of Things to make fetal dose tracking more effective.

Modified PEG-Lipids Enhance the Nasal Mucosal Immune Capacity of Lipid Nanoparticle mRNA Vaccines

Background/Objectives: Omicron, the predominant variant of SARS-CoV-2, exhibits strong immune-evasive properties, leading to the reduced efficacy of existing vaccines. Consequently, the development of versatile vaccines is imperative. Intranasal mRNA vaccines offer convenient administration and have the potential to enhance mucosal immunity. However, delivering vaccines via the nasal mucosa requires overcoming complex physiological barriers. The aim of this study is to modify PEGylated lipids to enhance the mucosal immune efficacy of the vaccine. Methods: The PEGylated lipid component of lipid nanoparticle (LNP) delivery vectors was modified with chitosan or mannose to generate novel LNPs that enhance vaccine adhesion or targeting on mucosal surfaces. The impact of the mRNA encoding the receptor-binding domain of Omicron BA.4/BA.5 on the immune response was examined. Results: Compared to the unmodified LNP group, the IgG and IgA titers in the chitosan or mannose-modified LNP groups showed an increasing trend. The chitosan-modified group showed better effects. Notably, the PEGylated lipid with 1.5 mol% of chitosan modification produced high levels of IgG1 and IgG2a antibodies, promoting Th1/Th2 responses while also generating high levels of IgA, which can induce stronger cellular immunity, humoral immunity, and mucosal immunity. Conclusions: The 1.5 mol% of chitosan-modified LNPs (mRNA-LNP-1.5CS) can serve as a safe and effective carrier for intranasal mRNA vaccines, offering a promising strategy for combating the Omicron variant.

Standalone single- and bi-layered human skin 3D models supported by recombinant silk feature native spatial organization

Physiologically relevant human skin models that include key skin cell types can be used forin vitrodrug testing, skin pathology studies, or clinical applications such as skin grafts. However, there is still no golden standard for such a model. We investigated the potential of a recombinant functionalized spider silk protein, FN-silk, for the construction of a dermal, an epidermal, and a bilayered skin equivalent (BSE). Specifically, two formats of FN-silk (i.e. 3D network and nanomembrane) were evaluated. The 3D network was used as an elastic ECM-like support for the dermis, and the thin, permeable nanomembrane was used as a basement membrane to support the epidermal epithelium. Immunofluorescence microscopy and spatially resolved transcriptomics analysis demonstrated the secretion of key ECM components and the formation of microvascular-like structures. Furthermore, the epidermal layer exhibited clear stratification and the formation of a cornified layer, resulting in a tight physiologic epithelial barrier. Our findings indicate that the presented FN-silk-based skin models can be proposed as physiologically relevant standalone epidermal or dermal models, as well as a combined BSE.

Functional Assessment of a Bioprinted Immuno-Mimetic Peyer's Patch Recapitulating Gut-Associated Lymphoid Tissue.

Gut immune models have attracted much interest in better understanding the microbiome in the human gastrointestinal tract. The gut-associated lymphoid tissue (GALT) has complex structures that interact with microorganisms, including the intestinal monolayer as a physiological barrier and the Peyer's patch (PP) involved in the immune system. Although essential for studying GALT and microbiome interactions, current research often uses simplified models that only recapitulate some components. In this study, GALT is recapitulated to consider the morphology and function of lymphocyte-containing PP beneath the intestinal monolayer and to analyze microbiome interaction. Using the bioprinting technique, a dome-shaped structure array for the PP is fabricated, and epithelial cells are cocultured to form the intestinal monolayer. The developed GALT model shows stable cell differentiation on the hydrogel while exhibiting durability against lipopolysaccharides. It also exhibits increased responsiveness to Escherichia coli, as indicated by elevated nitric oxide levels. In addition, the model underscores the critical role of GALT in maintaining bacterial coexistence and in facilitating immune defense against foreign antigens through the secretion of immunoglobulin A by lymphocyte spheroids. The proposed GALT model is expected to provide significant insights into studying the gut-immune system complexity and microbiome.

Developments in Emerging Topical Drug Delivery Systems for Ocular Disorders.

According to the current information, using nano gels in the eyes have therapeutic benefits. Industry growth in the pharmaceutical and healthcare sectors has been filled by nanotechnology. Traditional ocular preparations have a short retention duration and restricted drug bioavailability because of the eye's architectural and physiological barriers, a big issue for physicians, patients, and chemists. In contrast, nano gels can encapsulate drugs within threedimensional cross-linked polymeric networks. Because of their distinctive structural designs and preparation methods, they can deliver loaded medications in a controlled and sustained manner, enhancing patient compliance and therapeutic efficacy. Due to their excellent drugloading capacity and biocompatibility, nano-gels outperform other nano-carriers. This study focuses on using nano gels to treat eye diseases and provides a brief overview of their creation and response to stimuli. Our understanding of topical drug administration will be advanced using nano gel developments to treat common ocular diseases such as glaucoma, cataracts, dry eye syndrome, bacterial keratitis, and linked medication-loaded contact lenses and natural active ingredients.

Tetrahydropyrimidine Ionizable Lipids for Efficient mRNA Delivery.

Lipid nanoparticles (LNPs) have emerged as an effective and promising technology for messenger RNA (mRNA) delivery, offering a potential solution to physiological barriers and providing an alternative approach to gene therapy without the drawbacks associated with viral delivery. However, efficiently delivering mRNA remains a significant challenge in nucleic acid-based therapies due to the limitations of current LNP platforms in achieving optimal endosomal escape and mRNA release, which largely relies on finding a suitable ionizable lipid. Additionally, the synthesis of these ionizable lipids involves multiple chemical reactions, often making the process time-consuming and difficult to translate. In this study, we employed a facile, catalyst-free, and versatile one-pot multicomponent reaction (MCR) to develop a library of ionizable lipids featuring a pharmacologically significant tetrahydropyrimidine (THP) backbone, tailored for enhanced mRNA delivery. A library of 26 THP ionizable lipids was systematically synthesized in just 3 h and formulated with luciferase mRNA for initial in vitro screening. The THP LNPs exhibited tunable particle sizes, favorable ζ-potentials, and high encapsulation efficiencies. Among them, THP1 demonstrated the highest transfection efficiency both in vitro and in vivo after intramuscular administration, comparable to DLin-MC3-DMA (MC3), a conventional benchmark. Further optimization of THP1 with phospholipids significantly enhanced intramuscular mRNA delivery and showed sustained protein expression in vivo for up to 5 days. More importantly, it demonstrated successful intravenous delivery in a dose-dependent manner with minimal toxicity, as indicated by hematological, histopathological, and proinflammatory cytokine assessments. Furthermore, THP1 LNPs also demonstrated the ability to edit genes in specific liver tissues in a tdTomato transgenic mouse model, highlighting their precision and utility in targeted therapeutic applications. These findings position THP1 LNPs as promising candidates for advancing mRNA-based therapies, with significant implications for clinical translation in vaccine delivery and CRISPR/Cas9-mediated gene editing in the liver.

A Self-Assembled Transdermal Nanomedicines Incorporating Pendant Disulfides for Non-Invasive, Synergistic Treatment of Melanoma.

Transdermal drug delivery system (TDDS) offers lower systemic toxicity and good patient compliance, making it a promising treatment option for skin-related cancers. However, physiological barriers in the skin frequently impede the therapeutic efficiency of TDDS. To address this, a unique self-assembled TDDS that incorporates disulfide pendant groups (termed Sup-TDDS) is presented. It is formulated with dithiolane-containing lipoic acid (LA), photosensitizers Ce6, and chemotherapeutic agents trametinib. Pendant disulfide moieties on Sup-TDDS facilitate thiol-disulfide exchange reactions with exofacial thiols on cell surfaces, thus enhancing stratum corneum penetration. In contrast to intravenous injection, topical administration of Sup-TDDS can penetrate deeper into the skin (> 500 µm) and promote drug accumulation in subcutaneous tumors. In a B16F10-bearing mouse model, Sup-TDDS treatment demonstrates significant anti-tumor effects in primary and recurrent melanoma, benefiting from the synergistic effects of Ce6 and trametinib. These results underscore that Sup-TDDS's transdermal properties allow non-invasive melanoma therapy, implying the potential of nanodrugs containing pendant disulfides for transdermal treatment of skin illnesses.

Therapeutic Contact Lenses for Intraocular Drug Administration: Innovations and Applications in Treating Fungal Keratitis

This review examines the advancements in ocular medication administration, focusing on therapeutic contact lenses (TCLs) as a novel approach for treating fungal keratitis. Traditional eye Drops' bioavailability is poor due to various anatomical and physiological barriers, necessitating frequent administration and leading to poor patient compliance. TCLs offer a promising alternative, providing extended drug release, improved bioavailability, and enhanced patient comfort. This review explores different antifungal drugs, innovative methods for drug incorporation into TCLs, and their therapeutic efficacy. The potential of TCLs to revolutionize ocular drug delivery and improve treatment outcomes for fungal keratitis is discussed.

Advancements in Ocular Therapy: A Review of Emerging Drug Delivery Approaches and Pharmaceutical Technologies

Eye disorders affect a substantial portion of the global population, yet the availability of efficacious ophthalmic drug products remains limited. This can be partly ascribed to a number of factors: (1) inadequate understanding of physiological barriers, treatment strategies, drug and polymer properties, and delivery systems; (2) challenges in effectively delivering drugs to the anterior and posterior segments of the eye due to anatomical and physiological constraints; and (3) manufacturing and regulatory hurdles in ocular drug product development. The present review discusses innovative ocular delivery and treatments, encompassing implants, liposomes, nanoparticles, nanomicelles, microparticles, iontophoresis, in situ gels, contact lenses, microneedles, hydrogels, bispecific antibodies, and gene delivery strategies. Furthermore, this review also introduces advanced manufacturing technologies such as 3D printing and hot-melt extrusion (HME), aimed at improving bioavailability, reducing therapeutic dosages and side effects, facilitating the design of personalized ophthalmic dosage forms, as well as enhancing patient compliance. This comprehensive review lastly offers insights into digital healthcare, market trends, and industry and regulatory perspectives pertaining to ocular product development.

Delivery Aspects for Implementing siRNA Therapeutics for Blood Diseases.

Hematological disorders result in significant health consequences, and traditional therapies frequently entail adverse reactions without addressing the root cause. A potential solution for hematological disorders characterized by gain-of-function mutations lies in the emergence of small interfering RNA (siRNA) molecules as a therapeutic option. siRNAs are a class of RNA molecules composed of double-stranded RNAs that can degrade specific mRNAs, thereby inhibiting the synthesis of underlying disease proteins. Therapeutic interventions utilizing siRNA can be tailored to selectively target genes implicated in diverse hematological disorders, including sickle cell anemia, β-thalassemia, and malignancies such as lymphoma, myeloma, and leukemia. The development of efficient siRNA silencers necessitates meticulous contemplation of variables such as the RNA backbone, stability, and specificity. Transportation of siRNA to specific cells poses a significant hurdle, prompting investigations of diverse delivery approaches, including chemically modified forms of siRNA and nanoparticle formulations with various biocompatible carriers. This review delves into the crucial role of siRNA technology in targeting and treating hematological malignancies and disorders. It sheds light on the latest research, development, and clinical trials, detailing how various pharmaceutical approaches leverage siRNA against blood disorders, mainly concentrating on cancers. It outlines the preferred molecular targets and physiological barriers to delivery while emphasizing the growing potential of various therapeutic delivery methods. The need for further research is articulated in the context of overcoming the shortcomings of siRNA in order to enrich discussions around siRNA's role in managing blood disorders and aiding the scientific community in advancing more targeted and effective treatments.

Hydroxamate Siderophores Intensify the Co-Deposition of Cadmium and Silicon as Phytolith-Like Particulates in Rice Stem Nodes: A Natural Strategy to Mitigate Grain Cadmium Accumulation.

Sequestration of cadmium (Cd) in rice phytolith can effectively restrict its migration to the grains, but how hydroxamate siderophore (HDS) affects phytolith formation within rice plants especially the fate of Cd and silicon (Si) remains poorly understood. Here, we found that the addition of HDS increased the content of dissolved Si and Cd in soil pore water as well as its absorption by the rice roots during the reproductive growth stage. HDS effectively trapped orthosilicic acid and Cd ions at the third stem nodes of rice plants via hydrogen bonds and chelation interactions, which then rapidly deposited on the xylem cell wall through hydrophobic interactions. Ultimately, Cd was immobilized as phytolith-like particulates in the form of CdSiO3. Field experiments verified that Cd accumulation was significantly reduced by 46.4% in rice grains but increased by 41.2% in rice stems after HDS addition. Overall, this study advances our understanding of microbial metabolites enhancing the instinctive physiological barriers within rice plants.

Dynamic Liver Chip Based on Well-Coupled Microfluidics: An Accurate NASH Model for Drug Evaluation.

The convenient liver model in vitro recapitulating the hepatic functions, metabolism, and even steatohepatitis to perform the accurate drug evaluation is still challenging because of the unattainable hominine physiological microenvironment in vitro. Here, the progressed stages of nonalcoholic steatohepatitis (NASH) disease were precisely modeled to accurately evaluate the performance of antilipemic based on the dynamic liver chip adopting the well-coupled microfluidics, which well recapitulated the normal and steatohepatitis of liver in vitro. In brief, the mild nutrient flow and sufficient oxygen supply for parenchymal liver cells could be well supplied through the endothelial cells layer that mimicked the real physiological barrier of endothelium, while the loading of drugs might be obtained by directly adding drug into the running nutrient flow to mimic the intravenously administrable. The progressed degree of steatohepatitis could be directly reflected by the amount of intramyocellular lipid content (IMLC) of the HepG2 cell hepatocyte layer in wells that were induced by different concentrations of free fatty acids (FFA). To prove the concept of the liver chip in drug evaluation, an accurate assessment of the performance of firsocostat, the acetyl-CoA carboxylase (ACC) inhibitor of hepatic mitochondria of hepatocytes, was carried out. The subtle time dependence of firsocostat treatment to different progressed stages of NASH was clearly figured out. Therefore, we prospect the liver chip that adopted well-coupled microfluidics could be an accurate and standard liver model in vitro to carry out the antilipemic evaluation and screening, which significantly enlightens the drug evaluation by liver on chip in vitro.

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.

Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye

Ocular drug delivery presents significant challenges, attributed to the various anatomical and physiological barriers, as well as the limitations associated with conventional ocular formulations including low bioavailability, necessitating frequent dosing. The objective of the essay was to design sustained release nanofibrous inserts loaded with ceftazidime (CAZ), an antibiotic effective against gram-negative and gram-positive microorganisms, for the treatment of ocular infections. These nanofibers were fabricated using the electrospinning technique, employing biodegradable polymers such as polyvinyl alcohol (PVA), polycaprolactone (PCL) and Eudragit® (EUD). The nanofibrous inserts exhibited adequate mechanical strength for ocular use with an average diameter < 250 nm. In the initial 12-h period, a burst drug release was observed, followed by a controlled release for 120 h. Cell viability test confirmed the non-toxicity and safety of the nanofibers. The in vivo study demonstrated that the inserts sustain a drug concentration exceeding the minimum inhibitory concentration (MIC) of Pseudomonas aeruginosa and Staphylococcus aureus for 4 and 5 days, respectively. The AUC0–120 for CAZ-PVA-PCL was reported 11,882.81 ± 80.5 μg·h/mL and for CAZ-PVA-EUD was 9649.39 ± 86.84 μg·h/mL. The nanofibrous inserts' extended drug release maintains effective antimicrobial concentrations, avoids the fluctuations of eye drops, and, by being preservative-free, eliminates cytotoxicity.

Barriers that Inhaled Particles Encounter.

Inhalable particulate drug carriers-nano- and micro-particles, liposomes, and micelles-should be designed to promote drug deposition in the lung and engineered to exhibit the desired drug release property. To deposit at the desired site of action, inhaled particles must evade various lines of lung defense, including mucociliary clearance, entrapment by mucus layer, and phagocytosis by alveolar macrophages. Various physiological, mechanical, and chemical barriers of the respiratory system reduce particle residence time in the lungs, prevent particle deposition in the deep lung, remove drug-filled particles from the lung, and thus diminish the therapeutic efficacy of inhaled drugs. To develop inhalable drug carriers with efficient deposition properties and optimal retention in the lungs, particle engineers should have a thorough understanding of the barriers that particles confront and appreciate the lung defenses that remove the particles from the respiratory system. Thus, this section summarizes the mechanical, chemical, and immunological barriers of the lungs that inhaled particles must overcome and discusses the influence of these barriers on the fate of inhaled particles.

Exploring the potential of nanomedicine for gene therapy across the physicochemical and cellular barriers.

After COVID-19, a turning point in the way of pharmaceutical technology is gene therapy with beneficial potential to start a new medical era. However, commercialization of such pharmaceuticals would never be possible without the help of nanotechnology. Nanomedicine can fulfill the growing needs linked to safety, efficiency, and site-specific targeted delivery of Gene therapy-based pharmaceuticals. This review's goal is to investigate how nanomedicine may be used to transfer nucleic acids by getting beyond cellular and physicochemical barriers. Firstly, we provide a full description of types of gene therapy, their mechanism, translation, transcription, expression, type, and details of diseases with possible mechanisms that can only be treated with genes-based pharmaceuticals. Additionally, we also reviewed different types of physicochemical barriers, physiological and cellular barriers in nucleic acids (DNA/RNA) based drug delivery. Finally, we highlight the need and importance of cationic lipid-based nanomedicine/nanocarriers in gene-linked drug delivery and how nanotechnology can help to overcome the above-discussed barrier in gene therapy and their biomedical applications.

Nanoparticle Delivery of an Oligonucleotide Payload in a Glioblastoma Multiforme Animal Model.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain malignancy for which there is no cure. The blood-brain barrier is a significant hurdle in the delivery of therapies to GBM. Reported here is an image-guided, iron oxide-based therapeutic delivery nano platform capable of bypassing this physiological barrier by virtue of size and accumulating in the tumor region, delivering its payload. This 25 nm nano platform consists of crosslinked dextran-coated iron oxide nanoparticles labeled with Cy5.5 fluorescent dye and containing antisense oligonucleotide as a payload. The magnetic iron oxide core enables tracking of the nanoparticles through in vivo magnetic resonance imaging, while Cy5.5 dye allows tracking by optical imaging. This report details the monitoring of the accumulation of this nanoparticle platform (termed MN-anti-miR10b) in orthotopically implanted glioblastoma tumors following intravenous injection. In addition, it provides insight into the in vivo delivery of RNA oligonucleotides, a problem that has hampered the translation of RNA therapeutics into the clinic.

A Peptide-Drug Conjugate-Based Nanoplatform for Immunometabolic Activation and In Situ Nerve Regeneration in Advanced-Stage Alzheimer's Disease.

The formidable protection of physiological barriers and unclear pathogenic mechanisms impede drug development for Alzheimer's disease (AD). As defenders of the central nervous system, immune-metabolism function, and stemness of glial cells remain dormant during degeneration, representing a significant challenge for simultaneously targeting and modulating. Here, a modular nanoplatform is presented composed of peptide-drug conjugates and an inflammation-responsive core. The nanoplatform is transported through the blood-brain barrier via transcytosis and disassembles in the oxidative stress microenvironment upon intravenous administration. The released drug-conjugated modules can specifically target and deliver hydroxychloroquine (HCQ) and all-trans retinoic acid (ATRA) to microglia and astrocytes, respectively. The immune function of chronic tolerant microglia is activated by metabolic modulation, and reactive astrocytes trans-differentiate into functional neurons. In a transgenic mouse model, nanoplatform reduces levels of toxic proteins and inflammation while increasing neuronal density. This results in the amelioration of learning and memory decline. The modular nanoplatform provides design principles for multi-cellular targeting and combination nano-therapy for inflammation-related diseases.

A one-platform comparison study of brinzolamide-loaded liposomes, niosomes, transfersomes, and transniosomes for better management of glaucoma

Ocular drug delivery presents significant challenges due to various anatomical and physiological barriers. Ultradeformable vesicles have emerged as better vesicular systems for achieving deeper corneal penetration and enhanced ocular bioavailability. This research aims to develop a hybrid vesicular system with improved deformability and compare it to conventional vesicular carriers. The ultradeformable vesicle, termed “transniosomes,” is a combination of niosomes, liposomes, and transfersomes, loaded with brinzolamide as model drug. The brinzolamide-loaded transniosomes (BRZ-TN) was formulated and compared with different vesicular systems through in vitro, ex vivo, and in vivo characterizations. The optimized BRZ-TN demonstrated a vesicle size of 112.06 ± 4.13 nm and an entrapment efficiency of 93.63 ± 0.30 %. With a deformability index of 6.405, the BRZ-TN exhibited a permeability of 86.68 ± 2.51 % over 10 h, which is approximately 1.3 times higher than other conventional vesicular systems. Additionally, the BRZ-TN showed a drug flux of 0.247 ± 0.01 mg/cm2/h and an apparent permeability of 0.09 ± 1.21 cm/s. Pre-clinical experiments confirmed the superiority of the optimized BRZ-TN, achieving a 37 % reduction in intraocular pressure (IOP), post 6hr of administration, indicating its prolonged therapeutic effect and improved ocular bioavailability. The findings of this study suggest that transniosomes are superior to other carriers and hold great promise as a nanocarrier for ocular drug delivery.

Hydrogel-based formulations for urothelial cancer therapy.

Drug infusion therapy after surgery for urothelial carcinoma is an effective measure to reduce cancer recurrence rate. Hydrogels are drug carriers with good biocompatibility and high drug loading capacity, which can optimize the pharmacokinetics of drugs in the urinary system to improve the therapeutic effect. Compared with the traditional free drug in situ perfusion, the hydrogel drug loading system can still maintain effective drug concentration in the face of continuous urinary flushing due to its good mucosal adhesion effect. The significantly prolonged drug retention time can not only improve the therapeutic effect of drugs, but also reduce the discomfort and risk of urinary tract infections caused by frequent drug infusion, and improve patient compliance. In addition, the combination of hydrogel with nanoparticles and magnetic materials can also improve the mucosal permeability and targeting effect of the hydrogel drug loading system, so as to overcome the mucus layer of urinary epithelium and the physiological barrier of tumor and minimize the impact on normal tissue and cell functions. At present, the research of hydrogels for urothelial cancer treatment involves chemotherapy, immunotherapy, gene therapy, inhibition of metabolism and multi strategy synergistic therapy. This review summarizes the research progress of hydrogels for the treatment of urothelial carcinoma, hoping to provide a reference for the future research of safe, reliable, effective, and advanced hydrogels with little side effects.