Hydrogel Delivery System Research Articles

Intramyocardial delivery of injectable hydrogel with arctigenin alleviated myocardial ischemia-reperfusion injury in rats.

Arctigenin belongs to a major bioactive component of Fructus arctii and has been found with cardioprotective effects on rats with ischemia-reperfusion (I/R) injury. The application of arctigenin is limited due to poor water solubility and low bioavailability. Hydrogel drug delivery systems can improve the efficacy and safety of drugs, increase drug utilization, and reduce side effects. We hypothesized that hydrogels containing arctigenin would facilitate the effect of arctigenin and alleviate I/R injury in the rat heart. Presently, adult Sprague-Dawley (SD) rats were subjected to 1h of I/R injury, then hydrogels comprising arctigenin were implanted into the myocardium of rats. Triphenyl tetrazolium chloride staining, hematoxylin-eosin staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and Western blot were performed for evaluating the infarct size, histopathological, and vital protein alterations of hearts. It was discovered that the hydrogel combined with arctigenin abated apoptosis and reduced infarct size. In addition, the results of echocardiography and Masson staining suggested that the hydrogel with arctigenin improved cardiac function, restrained myocardial fibrosis, and activated AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). Collectively, the injectable hydrogel delivery system enhances the effect of arctigenin, which may play a protective role in I/R injury by activating AMPK and SIRT1.

Hydrogel delivery systems of functional substances for precision nutrition.

Hydrogel delivery systems based on polysaccharides and proteins have the ability to protect functional substances from chemical degradation, control/target release, and increase bioavailability. This chapter summarizes the recent progress in the utilization of hydrogel delivery systems for nutritional interventions. Various hydrogel delivery systems as well as their preparation, structure, and properties are given. The applications for the encapsulation, protection, and controlled delivery of functional substances are described. We also discuss their potential and challenges in managing chronic diseases such as inflammatory bowel disease, obesity, liver disease, and cancer, aiming at providing theoretical references for exploring novel hydrogel delivery systems and their practical prospects in precise nutritional interventions.

Unleashing the power of chlorogenic acid: exploring its potential in nutrition delivery and the food industry.

In the contemporary era, heightened emphasis on health and safety has emerged as a paramount concern among individuals with food. The concepts of "natural" and "green" have progressively asserted dominance in the food consumption market. Consequently, through continuous exploration and development, an escalating array of natural bioactive ingredients is finding application in both nutrition delivery and the broader food industry. Chlorogenic acid (CGA), a polyphenolic compound widely distributed in various plants in nature, has garnered significant attention. Abundant research underscores CGA's robust biological activity, showcasing notable preventive and therapeutic efficacy across diverse diseases. This article commences with a comprehensive overview, summarizing the dietary sources and primary biological activities of CGA. These encompass antioxidant, anti-inflammatory, antibacterial, anti-cancer, and neuroprotective activities. Next, a comprehensive overview of the current research on nutrient delivery systems incorporating CGA is provided. This exploration encompasses nanoparticle, liposome, hydrogel, and emulsion delivery systems. Additionally, the article explores the latest applications of CGA in the food industry. Serving as a cutting-edge theoretical foundation, this paper contributes to the design and development of CGA in the realms of nutrition delivery and the food industry. Finally, the article presents informed speculations and considerations for the future development of CGA.

Dental cementum anchored microspheres embedded in a self-healing hydrogel for the antibacterial, anti-inflammation, osteogenic, and anti-osteoclastic management of periodontitis disease.

Periodontitis, a prevalent chronic oral disease, poses a significant threat to periodontal tissues, often resulting in substantial attachment loss and tooth shedding. Leveraging the principles of bone affinity and the mechanism underlying tetracycline pigmentation of teeth, this study strategically employed tetracycline (TC) as a bone-affinity group. We modified TC on the surface of polylactic-co-glycolic acid copolymer (PLGA) microspheres (MSs) through covalent binding, and then loaded berberine (BBR) MSs into a thermosensitive self-healing hydrogel delivery system (BBR/TC-MS). It was verified that the BBR/TC-MS gel rapidly formed an in situ reservoir in the periodontal pocket upon injection, and the chelation between TC and cementum in the periodontal pocket enhanced the anchoring effect of the TC-modified microspheres on cementum, preventing their loss through gingival crevicular fluid. Subsequently, we proved in vitro and in vivo that the BBR/TC-MS gel has excellent bacteriostatic effects against the periodontal pathogenic bacteria Fusobacterium necrophorum (Fn), anti-inflammation property in periodontal and gingival tissues, and osteogenic effect by regulating the RANKL-RANK-OPG pathway to diminish osteoclast activity, thus continuously exerting antibacterial, anti-inflammatory, osteogenic, and anti-osteoclastic effects. This innovative approach holds promise as a targeted and effective strategy for combating multifaceted challenges posed by periodontitis.

Bio Evaluation of Lantibiotic Nisin Loaded Polyvinyl Alcohol – Sodium Alginate Crosslinked Hydrogel As Novel Dental Temporary Filling Material

The incidence of oro-dental disorders has emerged as a serious threat to the healthcare sector owing to the increasing complexity of the oral microbiome. Significant advances in biomaterial research have led to the advent of a plethora of drug delivery systems including nanocarriers, dendrimers, hydrogels and other kinds of stimuli-responsive polymeric biomaterials. Anti-microbial peptides (AMPs) have engendered considerable interest in the past decades as potential alternatives to traditional disinfecting agents and also emerged as potent antibiofilm agents. Among the most viable approaches in targeted drug delivery, hydrogels incorporated with AMPs are emerging as bio-functional platforms yielding increased stability and bioavailability. The antibacterial and antibiofilm activities of Nisin are studied using microbiological methods followed by the synthesis of Nisin loaded PVA-Alginate hydrogel for dental treatment. The physicochemical characteristics of Nisin loaded hydrogel were done by swelling behavior, release kinetics assay, FTIR spectroscopic methods and cytotoxicity studies. Nisin showed antibacterial activity towards clinical isolates of drug-resistant bacteria and the antibiofilm and anti-adhesion studies demonstrated that Nisin could control the bacterial count in the test sample. The polymerization of Nisin into hydrogels was done and the physico-chemical characterization of Nisin loaded hydrogel network could be envisaged as a potential drug delivery platform for oral infections. Nisin loaded PVA-Alginate biocompatible hydrogel exhibited apparent swellable, flexible, nonhaemolytic materials and active antimicrobial and nontoxic materials. Physicochemical properties of these Nisin loaded PVA-Alginate biocompatible hydrogels have great potential in biomaterial-based drug delivery systems in controlling the growth and proliferation of major oro-dental pathogens. This could be exploited for the temporary biocompatible dental filling materials to treat the caries. Exploring potential nisin loaded hydrogel delivery systems will provide a brighter future of more friendly, effective and personalized treatment to deal with dental caries.

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery.

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

Biomimetic and spatiotemporally sequential hydrogel delivery system with self-healing and adhesion: Triple growth factor for bone defect repair

The healing of bone defects depends on early revascularization for delivery of oxygen, nutrients, growth factors, and stem cells to the injury region but also elimination of metabolic wastes. In this research, the combination of rapidly released VEGF and sustained release of PDGF-BB from the chitosan microspheres in low crosslinked outer layer promoted angiogenesis and vascularization, and sustained release of BMP-2 from the microspheres in high crosslinked inner layer provided structural support and facilitated osteogenic differentiation. In the skull defect model and the subcutaneous implantation model, the combination of triple growth factors significantly accelerated the regeneration of vascularized bone compared with stimulation of sole BMP-2 or only combination of VEGF and PDGF-BB. Notably, the antibacterial effect of QCS/PF hydrogel could effectively avoid the infection risk caused by surgical implantation of Gram-positive Staphylococcus aureus. In brief, the spatiotemporal specificity of the three growth factors was established in the “sandwich” structure QCS/PF (quaternized chitosan (QCS) and the aldehyde group of Pluronic®F127 (PF)) hydrogel delivery system, and the controlled and sequential release of the three growth factors within 28 days was achieved to better repair bone defects.

Current drugs for HIV-1: from challenges to potential in HIV/AIDS

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (ACC008) are described. It is interestingly to note that the lack of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and the multipass transmembrane proteins serine incorporator 5 (SERINC5) may be one of the reasons for the enhanced infectivity of HIV-1. This discovery of SERINC3 and SERINC5 provides new ideas for HIV-1 medication development. Therefore, we believe that in treating AIDS, antiviral medications should be rationally selected for pre-exposure and post-exposure prophylaxis to avoid the emergence of drug resistance. Attention should be paid to the research and development of new drugs to predict HIV mutations as accurately as possible and to develop immune antibodies to provide multiple guarantees for the cure of AIDS.

Enhanced Chemo-Immunotherapy Strategy Utilizing Injectable Thermosensitive Hydrogel for The Treatment of Diffuse Peritoneal Metastasis in Advanced Colorectal Cancer.

Patients with colorectal cancer (CRC) and diffuse peritoneal metastasis (PM) are not eligible for surgical intervention. Thus, palliative treatment remains the standard of care in clinical practice. Systemic chemotherapy fails to cause drug accumulation at the lesion sites, while intraperitoneal chemotherapy (IPC) is limited by high clearance rates and associated complications. Given the poor prognosis, a customized OxP/R848@PLEL hydrogel delivery system has been devised to improve the clinical benefit of advanced CRC with diffuse PM. This system is distinguished by its simplicity, security, and efficiency. Specifically, the PLEL hydrogel exhibits excellent injectability and thermosensitivity, enabling the formation of drug depots within the abdominal cavity, rendering it an optimal carrier for IPC. Oxaliplatin (OxP), a first-line drug for advanced CRC, is cytotoxic and enhances the immunogenicity of tumors by inducing immunogenic cell death. Furthermore, OxP and resiquimod (R848) synergistically enhance the maturation of dendritic cells, promote the expansion of cytotoxic T lymphocytes, and induce the formation of central memory T cells. Moreover, R848 domesticates macrophages to an anti-tumor phenotype. OxP/R848@PLEL effectively eradicates peritoneal metastases, completely inhibits ascites production, and significantly prolongs mice lifespan. As such, it provides a promising approach to managing diffuse PM in patients with CRC without surgical indications.

Articular Cartilage Regeneration via Induced Chondrocyte Autophagy by Sustained Release of Leptin Inhibitor from Thermo-Sensitive Hydrogel through STAT3/REDD1/mTORC1 Cascade.

The pathophysiology of osteoarthritis (OA) is closely linked to autophagy abnormalities in articular chondrocytes, the sole mature cell type in healthy cartilage. Nevertheless, the precise molecular mechanism remains uncertain. Previous research has demonstrated that leptin activates mTORC1, thereby inhibiting chondrocyte autophagy during the progression of OA. In this study, it is demonstrated that the presence of leptin induces a substantial increase in the expression of STAT3, leading to a notable decrease in REDD1 expression and subsequent phosphorylation of p70S6K, a recognized downstream effector of mTORC1. Conversely, inhibition of leptin yields contrasting effects. Additionally, the potential advantages of utilizing a sustained intra-articular release of a leptin inhibitor (LI) via an injectable, thermosensitive poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA: PLEL) hydrogel delivery system for the purpose of investigating its impact on cartilage repair are explored. The study conducted on LI-loaded PLEL (PLEL@LI) demonstrates remarkable efficacy in inhibiting OA and displays encouraging therapeutic advantages in the restoration of subchondral bone and cartilage. These findings establish a solid foundation for the advancement of a pioneering treatment approach utilizing PLEL@LI for OA.

Molecularly engineered dual-network photothermal hydrogel delivery system with enhanced mechanical properties, antibacterial ability and angiogenic effect for accelerating wound healing

Bacterial infection caused by trauma and chronic wounds in the most mobile area remains a challenge in clinic. It is difficult to achieve the synergistic effects of antibacterial capacity and skin regeneration using conventional therapeutic methods. Developing a multi-functional hydrogel dressing that can cope with the complex wound environment will contribute to the healing and therapeutic effects. In this work, a novel Cur@PAM/TA-Cu photothermal hydrogel delivery system was prepared by engineering tannic acid (TA) into covalent cross-linked polyacrylamide (PAM) on which the chelating tannic acid-copper metal–polyphenolic network (TA-Cu MPN) was imposed to form dual-crosslinked networks, and the natural medicine curcumin was loaded eventually. The molecularly engineered dual-crosslinked networks resulted in enhanced mechanical properties including bio-adhesion, tensile strength and self-healing, which made the hydrogel suitable for dynamic wound and various application scenarios. In addition, the excellent photothermal capacity, antioxidant effect and biocompatibility of the hydrogel were demonstrated. Notably, this curcumin loaded photothermal hydrogel exhibited superior antibacterial capacity (almost 100% killing ratio to E. coli and S. aureus) under 808 nm laser irradiation. Meanwhile, the in vivo wound healing experiment results revealed that the anti-inflammation and proangiogenic effect of Cur@PAM/TA-Cu hydrogel successfully shortened the healing time of wound and the reconstruction of skin structure and function. Thus, this dual-crosslinked multi-functional hydrogel delivery system is a promising wound dressing for accelerating wound healing.

Photo-crosslinking modified sodium alginate hydrogel for targeting delivery potential by NO response

In recent years, the incidence of inflammatory bowel disease has gradually increased. Traditional drugs can reduce inflammation, but cannot be targeting released and often require the coordination with delivery systems. However, a good targeting performance delivery system is still scarce currently. Inflammation can trigger oxidative stress, producing large amounts of oxides such as nitric oxide (NO). Based on this, the present experiment innovatively designed a hydrogel delivery system with NO response that could be inflammation targeting. The hydrogel is composed of sodium alginate modified with glycerol methacrylate, crosslinked with NO response agent by photo-crosslinking method, which have low swelling (37 %) and good mechanical properties with a stable structure even at 55 °C. The results of in vitro digestion also indicated that the hydrogel had a certain tolerance to gastrointestinal digestion. And in the NO environment, it was interestingly found that the structure and mechanical properties of the hydrogels changed significantly. Moreover, hydrogels have good biocompatibility, which ensures their safe use in vivo. In conclusion, this NO-responsive-based delivery system is feasible and provides a new approach for drugs and active factors targeting delivery in the future.

Sustained Release of Neuroprotective Drugs Curcumin and Edaravone from Supramolecular Hydrogel for Ischemic Stroke Treatment

AbstractIschemic stroke is a major cause of death and disability worldwide. The poor drug delivery to cerebral ischemic regions remains a challenging issue for ischemic stroke treatment. Curcumin (Cur) and edaravone (EDV) show remarkable therapeutic effects on ischemic stroke. However, the short half‐life and poor aqueous solubility limit their application for long‐term and effective neuroprotection. Cur and EDV with a well‐studied hydrogelator Nap‐Phe‐Phe‐Tyr‐OH (NapFFY) is co‐assembled to prepare a novel supramolecular peptide hydrogel EDV/Cur/NapFFY, which can improve their bioavailability and transport the hydrophobic drugs to ischemic sites precisely by local administration. In vitro release test demonstrate that co‐assembly with NapFFY enables continuous release of Cur and EDV for about two weeks. Animal studies found that EDV/Cur/NapFFY hydrogel can effectively promote brain plasticity and enhance the functional recovery on the photothrombotic mouse model. Overall, the work reveales the great application potential of supramolecular peptide hydrogel delivery system EDV/Cur/NapFFY in promoting repair and recovery of ischemic stroke.

Magnetic-Responsive Liposomal Hydrogel Membranes for Controlled Release of Small Bioactive Molecules-An Insight into the Release Kinetics.

This work explores the unique features of magnetic-responsive hydrogels to obtain liposomal hydrogel delivery platforms capable of precise magnetically modulated drug release based on the mechanical responses of these hydrogels when exposed to an external magnetic field. Magnetic-responsive liposomal hydrogel delivery systems were prepared by encapsulation of 1,2-dipalmitoyl-sn-glycero-3-phosphocoline (DPPC) multilayered vesicles (MLVs) loaded with ferulic acid (FA), i.e., DPPC:FA liposomes, into gelatin hydrogel membranes containing dispersed iron oxide nanoparticles (MNPs), i.e., magnetic-responsive gelatin. The FA release mechanisms and kinetics from magnetic-responsive liposomal gelatin were studied and compared with those obtained with conventional drug delivery systems, e.g., free liposomal suspensions and hydrogel matrices, to access the effect of liposome entrapment and magnetic field on FA delivery. FA release from liposomal gelatin membranes was well described by the Korsmeyer-Peppas model, indicating that FA release occurred under a controlled diffusional regime, with or without magnetic stimulation. DPPC:FA liposomal gelatin systems provided smoother controlled FA release, relative to that obtained with the liposome suspensions and with the hydrogel platforms, suggesting the promising application of liposomal hydrogel systems in longer-term therapeutics. The magnetic field, with low intensity (0.08 T), was found to stimulate the FA release from magnetic-responsive liposomal gelatin systems, increasing the release rates while shifting the FA release to a quasi-Fickian mechanism. The magnetic-responsive liposomal hydrogels developed in this work offer the possibility to magnetically activate drug release from these liposomal platforms based on a non-thermal related delivery strategy, paving the way for the development of novel and more efficient applications of MLVs and liposomal delivery systems in biomedicine.

Polymer based dual drug delivery system for targeted treatment of fluoroquinolone resistant Staphylococcus aureus mediated infections

The present study attempts to treat S. aureus-induced soft skin infections using a combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, an efflux pump inhibitor molecule is synthesized and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP-loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained drug release for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation—solvent evaporation method, which showed optimum average particle size of 230–280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide a synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidence that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. The research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system for treating S. aureus-induced skin infections.

Meningeal lymphatics restoration and neurovascular protection synergistically improve traumatic brain injury treatment

Persistent neuroinflammation following traumatic brain injury (TBI) remains to be a significant challenge in the clinic, however, the role of meningeal lymphatics dysfunction related to neuroinflammation has been largely ignored in TBI pathogenesis. We found meningeal lymphatics exhibited hyperplasia but the lymphatic drainage was decreased in moderate open-skull TBI. Besides, surgical ligation of the efferent lymphatic exacerbated the microglia responses and deteriorated motor function. To tackle this problem, here we designed neuroinflammation-resolving hydrogel to enhance lymphatic drainage and provide a protective effect for neurovascular. Specifically, VEGF-C 156S and bone mesenchymal stem cells derived extracellular vehicles (EVs) loaded injectable gelatin-methacryloyl (GelMA) hydrogel delivery system is constructed for these bioactive components continuous release. Such delivery system not only promotes functional meningeal lymphangiogenesis and increases lymphatic drainage, but also provides neurovascular protection and reduces microglia activation. Moreover, VEGF-C 156S works synergistically with EVs in decreasing microglia activation, neuron loss, as well as promoting angiogenesis to enhance motor function. Overall, rejuvenation lymphatic drainage provides neurovascular protection for neurological function improvement could be a novel strategy for TBI treatment.

Codelivery of triptolide and IFN-γ to boost antitumor immunity for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a specific type of breast cancer that exhibits poor prognosis and complex tumor heterogeneity. The unique immune tumor microenvironment reveals great potential of immunotherapy in TNBC. Triptolide, a potential regulator of immune-related signaling, has shown potent antitumor activity in TNBC. However, the molecular mechanism of triptolide in TNBC is still controversial. This study identified interferon-γ (IFN-γ) as a therapeutical target of triptolide based on the analysis of prognostic biomarkers in TNBC. IFN-γ is an important component of immunotherapy and contributes to antitumor immune activation. Triptolide was found to significantly reverse the IFN-γ-inducible programmed death-ligand 1 (PD-L1) in TNBC. The combined treatment of triptolide and IFN-γ in a hydrogel delivery system remarkably induced the cytotoxic CD8 + T lymphocytes activation, showing a synergistic effect on the potent tumor inhibition.

Rational Design of Bioactive Hydrogels toward Periodontal Delivery: From Pathophysiology to Therapeutic Applications

AbstractPeriodontitis is a biofilm‐induced, host‐mediated inflammatory disease that results in periodontal tissue destruction. The design of functional biomaterials based on disease pathophysiology is essential for enhancing their therapeutic effects in periodontitis treatment. As promising localized drug delivery systems and tissue engineering scaffolds, hydrogels have gained significant interest for controlled and sustained release of bioactive agents in periodontal applications. The rational design of bioactive hydrogels can facilitate bacterial control and modulate destructive host inflammation, thereby preventing the progression of periodontitis. In this review, the pathophysiological mechanisms underlying periodontitis as fundamental principles for the design of functional hydrogel systems are first introduced. In the following part, an overview is systematically provided of the types and functions of the bioactive hydrogel systems loaded with anti‐bacterial and anti‐inflammatory agents for periodontal delivery. Finally, the remaining challenges and future perspectives of hydrogel delivery systems for periodontal applications are proposed. It is believed that this review will inspire the rational design and development of innovative functional hydrogel biomaterials toward periodontal therapy.

Multifunctional hydrogel delivery system for disease therapy

Multifunctional hydrogel delivery system for disease therapy

Nasal delivery of an immunotherapeutic vaccine in thermosensitive hydrogel against allergic asthma

Asthma poses a significant threat to public health, with an estimated burden of over 334 million people worldwide. Available treatments are often inadequate. We developed a thermo-sensitive hydrogel vaccine containing allergen and FK506 that induced immune tolerance via intranasal administration to treat experimental allergic asthma. The hydrogel delivery system was formulated based on Poloxamer 407 (P407), Carbopol 974P NF, and Polyoxyl 15 hydroxystearate (Kolliphor HS15, HS15). It flowed freely at room temperature and rapidly formed a hydrogel in the nasal cavity once the temperature rose over 33 °C. Ovalbumin and FK506 were slowly released from the hydrogel form and their mucosal residence time was significantly prolonged compared to the liquid formulation. In both an OVA-induced asthma model and an HDM-induced asthma model, the vaccines formulated in hydrogel gave lower levels of eosinophilic inflammation, and airway remodeling. The reduction of lung function was ameliorated, and Foxp3-expressing CD4 + Treg cells were significantly higher. The frequency of Foxp3 + Tregs in lung-draining lymph nodes (dLNs) was correlated with the amelioration. Depletion of Foxp3 + Treg cells abolished the beneficial effects of the allergen/FK506 hydrogel vaccinations. Thus, the allergen/FK506 hydrogel formulation has the potential to be a delivery system for therapeutic allergy vaccines to induce immune tolerance.