Prolonged Drug Retention Research Articles

Progress in the role of nanoparticles in the diagnosis and treatment of bone and joint tuberculosis

Bone and joint tuberculosis (BJTB), caused by Mycobacterium tuberculosis (MTB), is a prevalent form of extrapulmonary tuberculosis that poses significant challenges to global public health due to difficulties in early diagnosis, prolonged treatment cycles, and drug resistance. Recent advancements in nanotechnology have introduced novel solutions for the early detection and precise treatment of BJTB, leveraging unique physicochemical properties such as high specific surface area, targeted delivery capabilities, sustained drug release, and excellent biocompatibility. In diagnostic applications, nanomaterials markedly enhance the sensitivity and accuracy of detection methods while reducing testing time. These technologies are adaptable to resource-limited settings, enabling earlier patient intervention and mitigating disease progression risk. In therapeutic applications, nanomaterials prolong drug retention in bone tissue through targeted delivery, thereby decreasing medication frequency and minimizing toxic side effects, which significantly improves treatment efficacy. Despite substantial progress, further research is required to address long-term safety concerns, broaden clinical applicability, and evaluate performance under complex pathological conditions. This review summarizes recent advancements in nanomaterials for diagnosing and treating BJTB and identifies key areas for future research, laying the groundwork for advancing precision medicine and personalized treatments.

Formulation and Evaluation of Lipid/Soluplus-Stabilized Nanocrystals of Paclitaxel and Bosutinib for a Synergistic Effect in Non-Small Cell Lung Cancer Therapy.

Tyrosine kinase inhibitors have been employed for the treatment of lung cancer, owing to their role in regulating irregulated pathways or mutated genes. Bosutinib, a nonreceptor tyrosine kinase, has been recently investigated for lung cancer treatment. Bosutinib can also be used with paclitaxel as a combinatorial approach to receive a synergistic effect for the effective management of lung cancer. Furthermore, the nanocrystals of each can also be prepared and in combination can produce a more pronounced impact than the drug combination. Herein, the prepared Soluplus/lipid-stabilized nanocrystals of paclitaxel and bosutinib were rod to cubic in shape of about 150-250 nm. The nanocrystals were stable, provided controlled drug release, and exhibited a higher aerosolization performance. The nanocrystal combination demonstrated higher anticancer activity than the drug combination synergy against A549 cancer cells. The nanocrystals increased the level of cellular internalization in cancer cells, thereby inducing higher ROS generation and apoptosis of cancer cells. Furthermore, the lipid/Soluplus-stabilized nanocrystals exhibited higher translocation potential compared with only Soluplus-stabilized nanocrystals. The nanocrystals administered intratracheally showed a lower drug distribution to other organs, with prolonged drug retention in the lungs, suggesting the higher efficacy of developed nanocrystals in targeting the lungs. In conclusion, lipid-modified nanocrystals can be a novel approach for the effective management of lung cancer.

Melanin-Binding-Based Discovery of Topically Instilled Carbonic Anhydrase Inhibitors for Targeted Delivery and Prolonged Action in the Eye.

Glaucoma is a vision-threatening disease that is currently treated with intraocular-pressure-reducing eyedrops that are instilled once or multiple times daily. Unfortunately, the treatment is associated with low patient adherence and suboptimal treatment outcomes. We developed carbonic anhydrase II inhibitors (CAI-II) for a prolonged reduction of intraocular pressure (IOP). The long action is based on the melanin binding of the drugs that prolongs ocular drug retention and response. Overall, 63 new CAI-II compounds were synthesized and tested for melanin binding in vitro. Carbonic anhydrase affinity and IOP reduction of selected compounds were tested in rabbits. Prolonged reduction of IOP in pigmented rabbits was associated with increasing melanin binding of the compound. Installation of a single eye drop of a high melanin binder carbonic anhydrase inhibitor (CAI) resulted in ≈2 weeks' decrease of IOP, whereas the effect lasted less than 8 h in albino rabbits. Duration of the IOP response correlated with melanin binding of the compounds. Ocular pharmacokinetics of a high melanin binder compound was studied after eye drop instillation to the rat eyes. The CAI showed prolonged drug retention in the pigmented iris-ciliary body but was rapidly eliminated from the albino rat eyes. The melanin-bound drug depot maintained effective free concentrations of CAI in the ciliary body for several days after application of a single eye drop. In conclusion, melanin binding is a useful tool in the discovery of long-acting ocular drugs.

Functionalized amino acid-based injectable hydrogels for sustained drug delivery.

Drug delivery vehicles optimize therapeutic outcomes by enhancing drug efficacy, minimizing side effects, and providing controlled release. Injectable hydrogels supersede conventional ones in the field of drug delivery owing to their less invasive administration and improved targeting. However, they face challenges such as low biodegradability and biocompatibility, potentially compromising their effectiveness. To address these limitations, a modified amino acid-based pH-responsive injectable shear-thinning hydrogel cl-β-CD-g-p(Gly-MA) has been developed as an efficient drug carrier. In the two-step synthetic approaches, first, the well-known amino acid glycine (Gly) is modified to form glycine methacrylate (Gly-MA). Afterward, Gly-MA is chemically crosslinked with β-cyclodextrin (β-CD), an oligosaccharide, using an ethylene glycol dimethacrylate (EGDMA) crosslinker. The presence of these biomaterials as building blocks enhances the biocompatibility, hemocompatibility, and biodegradability of the hydrogel. They also reduce the risk of immunogenicity. The unique property of easy injectability enables minimally invasive administration. This feature also helps prolong drug retention at the target site, further optimizing drug delivery efficiency. Moreover, the pH-responsive feature of the developed cl-β-CD-g-p(Gly-MA) hydrogel ensures controlled drug release in response to the physiological conditions of the target site, enhancing therapeutic efficacy. The study focuses on investigating the in vitro loading and release of diclofenac sodium (DS), a non-steroidal anti-inflammatory drug (NSAID) commonly used to treat arthritic pain and inflammation.

Advances in Drug Delivery Systems for Atopic Dermatitis Treatment.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritus and impaired skin barrier function. Advances in drug delivery systems have transformed AD treatment by enhancing drug stability, bioavailability, and targeted delivery. Drug delivery systems such as liposomes, hydrogels, and microneedles enable deeper skin penetration, prolonged drug retention, and controlled release, reducing side effects and treatment frequency. Liposomes improve drug absorption and stability, while hydrogels offer high water content and responsive drug release. Microneedles facilitate painless, localized drug delivery, enhancing patient compliance. These systems address the limitations of traditional therapies like topical corticosteroids and systemic immunosuppressants, which are associated with adverse effects and poor patient adherence. Recent innovations include Janus kinase (JAK) inhibitors and biologics targeting immune pathways, demonstrating significant efficacy in reducing inflammation and symptoms. Drug delivery systems offer a safer, more efficient alternative for delivering these advanced therapies. By improving therapeutic outcomes and patient experience, drug delivery systems represent a crucial advancement in AD management.

Manipulation of Lipid Nanocapsules as an Efficient Intranasal Platform for Brain Deposition of Clozapine as an Antipsychotic Drug.

The blood-brain barrier (BBB) significantly limits the treatment of central nervous system disorders, such as schizophrenia, by restricting drug delivery to the brain. This study explores the potential of intranasal clozapine-loaded lipid nanocapsules (IN LNCsClo) as a targeted and effective delivery system to the brain. LNCsClo were prepared using the phase inversion technique and characterized in terms of size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. The pharmacokinetic, safety, and pharmacodynamic effects of LNCsClo were then evaluated in a rat model through intranasal (IN) administration and compared with those of oral and intravenous (IV) Clo solutions. LNCsClo were prepared using a phase inversion technique, resulting in a nanocarrier with a particle size of 28.6 ± 3.6 nm, homogenous dispersion, and high EE% (84.66 ± 5.66%). Pharmacokinetic analysis demonstrated that IN LNCsClo provided enhanced Clo brain bioavailability, rapid CNS targeting, and prolonged drug retention compared to oral and intravenous routes. Notably, the area under the curve (AUC) for brain concentration showed more than two-fold and eight-fold increases with LNCsClo, compared to IV and oral solutions, respectively, indicating improved brain-targeting efficiency. Safety assessments indicated that LNCsClo administration mitigated Clo-associated metabolic side effects, such as hyperglycemia, insulin imbalance, and liver enzyme alterations. Additionally, pharmacodynamic studies showed that LNCsClo significantly improved antipsychotic efficacy and reduced schizophrenia-induced hyperactivity, while preserving motor function. These results highlight the potential of IN LNCsClo as a novel drug delivery system, offering improved therapeutic efficacy, reduced systemic side effects, and better patient compliance in the treatment of schizophrenia and potentially other CNS disorders.

Enhanced Ocular Drug Delivery of Dexamethasone Using a Chitosan-Coated Soluplus®-Based Mixed Micellar System.

This study introduces a novel dexamethasone (DEX) mixed micellar system (DEX-MM) using Soluplus® and Pluronic F-127 (PF127) to enhance ocular drug delivery. The enhancement of ocular application properties was achieved by creating a chitosan-coated DEX-MM (DEX-CMM), which promotes better adherence to the ocular surface, thereby improving drug absorption. Using the solvent evaporation method, a formulation was developed with a Soluplus®-to-drug ratio of 1:10, enhanced with 0.25% PF127. After dispersing in water, 1% chitosan (CS) was added. The stability and integrity of DEX within the micelles were verified using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Additionally, in vitro and ex vivo drug release studies were conducted. DEX-CMM (F6) demonstrated a particle size of 151.9 ± 1 nm and a polydispersity index (PDI) of 0.168 ± 0.003, suggesting uniformity and high electrostatic stability with a zeta potential of +35.96 ± 2.13 mV. The non-Fickian drug release mechanism indicated prolonged drug retention. Comparative analyses showed DEX-CMM outperforming a standard DEX suspension in drug release and ocular tissue permeation, with flux measurements significantly higher than the DEX suspension. The study confirmed the efficacy of DEX-CMM in enhancing drug delivery to ocular tissues, evidenced by improved permeability. Safety evaluations using the HET-CAM test demonstrated that DEX-CMM was non-irritant, supporting its potential for effective 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.

In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.

Development of an In-situ Nasal Gel Formulation of Bepotastine Besilate for the Treatment of Allergic Rhinitis

The objective of this research was to formulate and evaluate mucoadhesive in situ nasal gels as a novel delivery system for Bepotastine Besilate. Aiming to provide sustained drug release directly at the site of action, thereby reducing the need for frequent dosing due to the drug's rapid absorption and short half-life. A series of eight formulations were developed using varying ratios of Poloxamer 407 and Poloxamer 188. The formulations exhibited a visually clear sol phase, indicating uniform dispersion of ingredients, with gelling temperatures ranging from 33.3±0.41 to 36.7±0.73°C. The gelling time, an important parameter for user convenience and efficacy, ranged from 15.7±01.52 to 43.3±20.80 s, meeting practical application requirements. Furthermore, all formulations consistently achieved a drug content of over 95%, ensuring dosage uniformity and efficacy. The pH values of the formulations were within the acceptable range of 6.13±0.10 to 6.91±0.02, minimizing the risk of mucosal irritation upon application. Importantly, the mucoadhesive strength ranged from 1056±0.32 to 6456± 045 dyne/cm², indicating robust adhesion to nasal mucosa, which is critical for prolonged drug retention and sustained release. In vitro drug release studies demonstrated sustained release profiles exceeding 4 hours for all formulations, following Higuchi kinetics, suggesting controlled drug release from the gel matrix. Accelerated stability studies corroborated the formulations' stability over the test period, indicating their potential for long-term storage and commercial viability. Additionally, FTIR analysis revealed no evidence of drug-polymer interactions, confirming the compatibility of Bepotastine Besilate with the selected polymer matrix. These comprehensive findings support the potential of in situ nasal gels as an effective and promising strategy for enhancing the therapeutic efficacy of Bepotastine Besilate, thereby improving patient outcomes.

From Liquid to Solid: Unravelling the Magic of In-Situ Gels

Abstract: In situ gelling formulations are liquid at room temperature and transform into gels upon application to the body in response to various stimuli (e.g., pH, temperature, ionic composition). Incorporating drug nanoparticles into these systems enhances their biomedical utility by prolonging drug release, reducing dosing frequency, and improving patient outcomes. These formulations, particularly those with mucoadhesive polymers, offer promising potential for targeted drug delivery and prolonged drug retention at specific sites. A review of clinical properties of in situ gelling systems investigated over the past decade underscores their effectiveness and challenges in achieving optimal dosage forms.

PH-responsive self-assembling peptides potentiate therapeutic efficacy via prolonged drug retention and immunomodulation

Insufficient drug accumulation at tumor sites is one of the key factors leading to treatment failure in breast cancer (BC), and developing a chemotherapeutic drug delivery system that can improve the immune microenvironment to expand the benefits of immunochemotherapy for BC remains a challenge. To increase the efficacy of BC treatment by extending drug retention at the tumor site, we developed a pH-responsive peptide modified with the PHSCN peptide sequence (Pep1) that self-assembles to form spherical DM/Pep1 nanoparticles after encapsulating doxorubicin (DOX) and metformin (MET). In the acidic tumor microenvironment, spherical nanocarriers transform into aggregates with a high aspect ratio, facilitating DOX and MET release for combined chemotherapy and immunomodulation. In cellular experiments, this construct provided prolonged drug retention in BC cells. In a subcutaneous tumor mouse model, the DM/Pep1 nanoparticles exhibited a superior tumor inhibition effect compared to that of free DOX/MET. The DM/Pep1 nanocomplex upregulated CD4, induced calreticulin (CRT) exposure, downregulated PD-L1, and enhanced the MET-mediated antitumor immune response. The use of this pH-responsive peptide nanocarrier system with morphological transformation offers a promising strategy for BC therapy.

Telmisartan loading thermosensitive hydrogel repairs gut epithelial barrier for alleviating inflammatory bowel disease

Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.

A Protocol for Preparing Mucoadhesive Emulsion Microgels and Assessing Their Mucoadhesion Properties In Vitro.

Intravesical instillation is an efficient therapeutic technique based on targeted administration of a drug directly into the lesion for the treatment of bladder diseases. This is an alternative to traditional systemic administration of drugs. However, this technique requires repeated procedures, which can lead to even greater inflammation and infection of the urethra. To date, novel systems that allow prolonged drug retention in the bladder cavity are actively being developed. We recently reported a targeted drug delivery system based on the mucoadhesive emulsion microgels consisting of the natural component whey protein isolate. Such micron-sized carriers possess high loading capacity, a prolonged drug release profile, and efficient mucoadhesive properties to the bladder urothelium. As a continuation of this work, we present a protocol for the synthesis of mucoadhesive emulsion microgels. Detailed procedures for preparing precursor solutions as well as studying the physico-chemical parameters of microgels (including loading capacity and drug release rate) and the mucoadhesive properties using the model of porcine bladder urothelium are discussed. Precautionary measures and nuances that are worth paying attention to during each experimental stage are given as well. Key features • The protocol for the synthesis of mucoadhesive emulsion microgels based on whey protein isolate is presented. The experimental conditions of emulsion microgels synthesis are discussed. • Methods for studying the physico-chemical properties of mucoadhesive emulsion microgels (size of emulsion microgels particles, loading capacity, release kinetics) are described. • The method for assessing mucoadhesive properties of emulsion microgels is demonstrated using the porcine bladder tissue model ex vivo.

Nanostructured lipid carriers loaded into in situ gels for breast cancer local treatment

In this study, nanostructured lipid carriers (NLC) were developed and employed to obtain in situ thermosensitive formulations for the ductal administration and prolonged retention of drugs as a new strategy for breast cancer local treatment. NLC size was influenced by the type and concentration of the oil phase, surfactants, and drug incorporation, ranging from 221.6 to 467.5 nm. The type of liquid lipid influenced paclitaxel and 5-fluorouracil cytotoxicity, with tributyrin-containing NLC reducing IC50 values by 2.0–7.0-fold compared to tricaprylin NLC in MCF-7, T-47D and MDA-MB-231 cells. In spheroids, the NLCs reduced IC50 compared to either drug solution (3.2–6.2-fold). Although a significant reduction (1.26 points, p < 0.001) on the health index of Galleria mellonella larvae was observed 5 days after NLC administration, survival was not significantly reduced. To produce thermosensitive gels, the NLCs were incorporated in a poloxamer (11 %, w/w) dispersion, which gained viscosity (2-fold) at 37 °C. After 24 h, ∼53 % of paclitaxel and 83 % of 5-fluorouracil were released from the NLC; incorporation in the poloxamer gel further prolonged release. Intraductal administration of NLC-loaded gel increased the permanence of hydrophilic (2.2–3.0-fold) and lipophilic (2.1–2.3-fold) fluorescent markers in the mammary tissue compared to the NLC (as dispersion) and the markers solutions. In conclusion, these results contribute to improving our understanding of nanocarrier design with increased cytotoxicity and prolonged retention for the intraductal route. Tributyrin incorporation increased the cytotoxicity of paclitaxel and 5-fluorouracil in monolayer and spheroids, while NLC incorporation in thermosensitive gels prolonged tissue retention of both hydrophilic and hydrophobic compounds.

A dual drug-loaded peptide system with morphological transformation prolongs drug retention and inhibits breast cancer growth

The treatment of breast cancer relies heavily on chemotherapy, but chemotherapy is limited by the disadvantages of poor targeting, susceptibility to extracellular matrix (ECM) interference and a short duration of action in tumor cells. To address these limitations, we developed an amphipathic peptide containing an RGD motif, Pep1, that encapsulated paclitaxel (PTX) and losartan potassium (LP) to form the drug-loaded peptide PL/Pep1. PL/Pep1 self-assembled into spherical nanoparticles (NPs) under normal physiological conditions and transformed into aggregates containing short nanofibers at acidic pH. The RGD peptide facilitated tumor targeting and the aggregates prolonged drug retention in the tumor, which allowed more drug to reach and accumulate in the tumor tissue to promote apoptosis and remodel the tumor microenvironment. The results of in vitro and in vivo experiments confirmed the superiority of PL/Pep1 in terms of targeting, prolonged retention and facilitated penetration for antitumor therapy. In conclusion, amphipathic peptides as coloaded drug carriers are a new platform and strategy for breast cancer chemotherapy.

Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Stepwise Targeting and Tandem Responsive Peptide Nanoparticles Enhance Immunotherapy through Prolonged Drug Retention

Stepwise Targeting and Tandem Responsive Peptide Nanoparticles Enhance Immunotherapy through Prolonged Drug Retention

Injectable Bioadhesive Hydrogels Scavenging ROS and Restoring Mucosal Barrier for Enhanced Ulcerative Colitis Therapy.

Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.

Strategies to prolong drug retention in solid tumors by aggregating Endo-CMC nanoparticles

Developing a highly effective nano-drug delivery system with sufficient drug permeability and retention in tumors is still a major challenge for oncotherapy. Herein, a tumor microenvironment responsive, aggregable nanocarriers embedded hydrogel (Endo-CMC@hydrogel) was developed to inhibit the tumoral angiogenesis and hypoxia for enhanced radiotherapy. The antiangiogenic drug (recombinant human endostatin, Endo) loaded carboxymethyl chitosan nanoparticles (Endo-CMC NPs) was wrapped by 3D hydrogel to comprise the Endo-CMC@hydrogel. After peritumoral injection, the Endo-CMC NPs were released, invaded deeply into the solid tumor, and cross-linked with intratumoral calcium ions. The cross-linking process enabled these Endo-CMC NPs to form larger particles, leading to long retention in tumor tissue to minimize premature clearance. This Endo-CMC@hydrogel, integrating the abilities of good tumoral penetration, long retention of anti-drug, and alleviation of hypoxia in tumor tissue, greatly improved the therapeutic effect of radiotherapy. This work provides a proof-of-concept of tumor microenvironment-responding and an aggregable nano-drug delivery system as promising antitumor drug carriers for effective tumor therapy.