Hydrogels For Delivery Research Articles

Hydrogels as local depots for on-demand therapeutic delivery: potential therapeutic approaches for tumor metastasis

Potential application of hydrogels for local delivery of therapeutics for tumor metastasis.

A photocrosslinkable and anti-inflammatory hydrogel of loxoprofen-conjugated chitosan methacrylate.

Polymer-drug conjugates are widely used for drug delivery. Herein, we report an injectable hydrogel for local delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) using chitosan (CS) as a carrier polymer. Loxoprofen (LOX) was conjugated to the backbone of CS via carbodiimide chemistry to obtain the LOX-CS conjugate. This conjugation transformed the water-insoluble unmodified CS into the water-soluble LOX-CS conjugate. In particular, the LOX-CS conjugate did not precipitate at pH 7, allowing smooth subsequent chemical modification with methacrylic anhydride (MA) to synthesize LOX-CS methacrylate (LOX-CS-MA) with significantly higher methacrylation substitution. The LOX-CS-MA was capable of in situ gel formation under visible light irradiation in the presence of a benzoin-2,4,6-trimethylbenzoylphosphinate lithium (LAP) photoinitiator. Our results show that the LOX-CS-MA hydrogel exhibited good cytocompatibility and blood compatibility. It promoted M2 polarization, inhibited pro-inflammatory gene expression, and upregulated anti-inflammatory gene expression of macrophages. Furthermore, the LOX-CS-MA hydrogel significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) produced by lipopolysaccharide (LPS)-stimulated macrophages. A subcutaneous implanted LOX-CS-MA hydrogel in a rat model revealed significantly reduced inflammatory cell density, decreased cell infiltration, and a much thinner fibrous capsule compared to the CS methacrylate (CS-MA) hydrogel, thus markedly alleviating the inflammatory response. This study highlights the feasibility of CS-drug conjugates in preparing CS-based methacrylate hydrogels for sustained drug release.

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.

Nanoparticles incorporated hydrogels for delivery of antimicrobial agents: developments and trends.

The prevention and treatment of microbial infections is an imminent global public health concern due to the poor antimicrobial performance of the existing antimicrobial regime and rapidly emerging antibiotic resistance in pathogenic microbes. In order to overcome these problems and effectively control bacterial infections, various new treatment modalities have been identified. To attempt this, various micro- and macro-molecular antimicrobial agents that function by microbial membrane disruption have been developed with improved antimicrobial activity and lesser resistance. Antimicrobial nanoparticle-hydrogels systems comprising antimicrobial agents (antibiotics, biological extracts, and antimicrobial peptides) loaded nanoparticles or antimicrobial nanoparticles (metal or metal oxide) constitute an important class of biomaterials for the prevention and treatment of infections. Hydrogels that incorporate nanoparticles can offer an effective strategy for delivering antimicrobial agents (or nanoparticles) in a controlled, sustained, and targeted manner. In this review, we have described an overview of recent advancements in nanoparticle-hydrogel hybrid systems for antimicrobial agent delivery. Firstly, we have provided an overview of the nanoparticle hydrogel system and discussed various advantages of these systems in biomedical and pharmaceutical applications. Thereafter, different hybrid hydrogel systems encapsulating antibacterial metal/metal oxide nanoparticles, polymeric nanoparticles, antibiotics, biological extracts, and antimicrobial peptides for controlling infections have been reviewed in detail. Finally, the challenges and future prospects of nanoparticle-hydrogel systems have been discussed.

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.

Composite alginate-based hydrogel delivery of antioxidant pumpkin protein hydrolysate in simulated gastrointestinal condition

Pumpkin seeds are rich in protein (24–36.5%). Some of them are consumed as nuts, while others are regarded as waste and used for feeding animals. Protein hydrolysates from pumpkin seeds possess some bioactive properties, such as anti-oxidant activity. In this work, various composite alginate hydrogels contain Aloe vera, CMC, and tragacanth have been employed to protect PSPH against degradation in simulated gastrointestinal digestion (SGI) and regulate its release rate. The encapsulation efficiency of PSPH in plain alginate and beads with Aloe vera, CMC, and tragacanth combinations was 71.63, 75.63, 85.07, and 80.4%, respectively. The release rate of the plain alginate beads was %30.23 in the SGF and %52.26 in the SIF, and decreased in the composite-based beads. The highest decreasing rate in the antioxidant activity during SGI was observed in free PSPH, and the decreasing rate slowed down in the alginate-based composites. The swelling rate in plain alginate was %-23.43 and %25.43 in the SGF and SIF, respectively, and increased in the composite-based beads. The FTIR spectra of hydrogels before and after loading with PSPH showed identical absorption patterns and were similar to each other. Based on the data for SEM, it was revealed that substituting other polymers in polymer combinations with alginates resulted in a porosity reduction of the beads and smoother and more uniform surfaces. Based on the results, the combination of polysacchared with alginate could protect and increase the applicability of PSPH as a functional component in the food industry.

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.

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.

Bigels for controlled gastric release of ascorbic acid: Impact on rheology, texture, thermal stability and antioxidant activity

Ascorbic acid (AA) is a vital nutrient to maintain critical physiological functions but is very sensitive to processing and storage. This can be overcome by using gel-based systems for controlled release of AA. This study compares various gel-based formulations such as hydrogel, emulsion gel, bigel (25 %, 50 %, and 75 % oleogel), and emulsions for thermal stability and delivery of AA, rheological and textural profile, encapsulation efficiency (>97 %), in vitro gastrointestinal release profile, and the corresponding antioxidant profile. An increase in the oleogel content increased the hardness (125 – 216 g) and viscoelastic properties (G′ and G′′) but decreased (76.16 – 25.86 %) the swelling ratio of the bigel. A spontaneous release of AA was witnessed during gastric digestion from emulsion gels (95 %), hydrogels (98 %) and emulsions, whereas a gradual and controlled gastric release of AA could be achieved by bigels. However, a sudden decrease in AA (70 – 80 % reduction) and a spike in dehydroascorbic acid (DHA, oxidized AA) could be observed during intestinal digestion. The bioaccessibility was highest for emulsion gel and bigel (87 %) and lowest for emulsions (70 %). Bigels with higher oleogel content also showed better thermal stability but their physical stability was compromised at higher temperature. The DPPH and ABTS activity was proportional to AA, while FRAP was impacted by both DHA and AA. Thus bigels could be utilised for controlled gastric release of AA with better thermal stability.

Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord

Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.

Injectable Methacrylated Gelatin Hydrogel for Safe Sodium Hypochlorite Delivery in Endodontics.

Keeping sodium hypochlorite (NaOCl) within the root canal is challenging in regenerative endodontics. In this study, we developed a drug delivery system using a gelatin methacryloyl (GelMA) hydrogel incorporated with aluminosilicate clay nanotubes (HNTs) loaded with NaOCl. Pure GelMA, pure HNTs, and NaOCl-loaded HNTs carrying varying concentrations were assessed for chemo-mechanical properties, degradability, swelling capacity, cytocompatibility, antimicrobial and antibiofilm activities, and in vivo for inflammatory response and degradation. SEM images revealed consistent pore sizes of 70-80 µm for all samples, irrespective of the HNT and NaOCl concentration, while HNT-loaded hydrogels exhibited rougher surfaces. The hydrogel's compressive modulus remained between 100 and 200 kPa, with no significant variations. All hydrogels demonstrated a 6-7-fold mass increase and complete degradation by the seventh day. Despite an initial decrease in cell viability, all groups recovered to 65-80% compared to the control. Regarding antibacterial and antibiofilm properties, 12.5 HNT(Double) showed the highest inhibition zone on agar plates and the most significant reduction in biofilm compared to other groups. In vivo, the 12.5 HNT(Double) group displayed partial degradation after 21 days, with mild localized inflammatory responses but no tissue necrosis. In conclusion, the HNT-NaOCl-loaded GelMA hydrogel retains the disinfectant properties, providing a safer option for endodontic procedures without harmful potential.

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.

Inorganic metal salts as additives in the design of cellulose/arabinogalactan hydrogels for prolonged delivery of simvastatin in simulated bio‐fluids

AbstractIn this study, carboxymethylcellulose and arabinogalactan were used to create an interpenetrating network (IPN) hydrogel system in the presence of AlCl3 alone or in combination with ZnSO4 salts. Ionotropic gelation caused the polymer sol droplets to transform into hydrogel particles in the presence of salts. The impact of salts on hydrogel properties was evaluated in terms of morphology, drug entrapment efficiency, swelling, and drug release kinetics. The cellulose IPN hydrogel particles containing 50% arabinogalactan looked spherical with evidence of surface folding when treated with AlCl3. Surface folding was reduced by an additional treatment with ZnSO4. Following treatment of the IPN particles with dual salts, a maximum drug entrapment efficiency of 88.77% was obtained. Surface erosion, as seen with aluminum‐IPN hydrogel particles, was minimized with the use of mixed salts as gelation medium. Furthermore, the use of mixed salts allowed the hydrogel particles to swell and consistently release simvastatin in simulated gastrointestinal fluids for up to 9 h. Thermal and x‐ray analyses revealed that the crystallinity of the drug reduced considerably after entrapment in the IPN hydrogel matrix. The infrared spectra analysis did not indicate any evidence of drug polymer interaction. The release of drug from the IPN hydrogel particles followed non‐Fickian diffusion mechanism. The dual metallic salts were found to be effective in creating physically stable cellulose‐arabinogalactan IPN hydrogel particles for sustained release of simvastatin in a varying pH environment of gastrointestinal tract.Highlights Dual inorganic salts allowed synthesis of cellulose/arabinogalactan hydrogel Additional use of ZnSO4 improved surface morphology of hydrogel particles Compatible environment of hydrogels allowed more than 88% drug entrapment Concentration of neutral arabinogalactan was crucial in dictating drug release Mixed salts controlled swelling and release of simvastatin from hydrogels

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.

Nanoengineered injectable hydrogels derived from layered double hydroxides and alginate for sustained release of protein therapeutics in tissue engineering applications

Chronic Kidney Disease (CKD) which involves gradual loss of kidney function is characterized by low levels of a glycoprotein called Erythropoietin (EPO) that leads to red blood cell deficiency and anemia. Recombinant human EPO (rhEPO) injections that are administered intravenously or subcutaneously is the current gold standard for treating CKD. The rhEPO injections have very short half-lives and thus demands frequent administration with a risk of high endogenous EPO levels leading to severe side effects that could prove fatal. To this effect, this work provides a novel approach of using lamellar inorganic solids with a brucite-like structure for controlling the release of protein therapeutics such as rhEPO in injectable hydrogels. The nanoengineered injectable system was formulated by incorporating two-dimensional layered double hydroxide (LDH) clay materials with a high surface area into alginate hydrogels for sustained delivery. The inclusion of LDH in the hydrogel network not only improved the mechanical properties of the hydrogels (5–30 times that of alginate hydrogel) but also exhibited a high binding affinity to proteins without altering their bioactivity and conformation. Furthermore, the nanoengineered injectable hydrogels (INHs) demonstrated quick gelation, injectability, and excellent adhesion properties on human skin. The in vitro release test of EPO from conventional alginate hydrogels (Alg-Gel) showed 86% EPO release within 108 h while INHs showed greater control over the initial burst and released only 24% of EPO in the same incubation time. INH-based ink was successfully used for 3D printing, resulting in scaffolds with good shape fidelity and stability in cell culture media. Controlled release of EPO from INHs facilitated superior angiogenic potential in ovo (chick chorioallantoic membrane) compared to Alg-Gel. When subcutaneously implanted in albino mice, the INHs formed a stable gel in vivo without inducing any adverse effects. The results suggest that the proposed INHs in this study can be utilized as a minimally invasive injectable platform or as 3D printed patches for the delivery of protein therapeutics to facilitate tissue regeneration.

Stimuli-responsive nanoparticles delivered by a nasal-brain pathway alleviate depression-like behavior through extensively scavenging ROS.

Depression is one of the most common mental diseases, which seriously affects patients' physical and mental health. Emerging evidence has indicated that oxidative stress (OS) is a major cause of neurodegeneration involved in the pathogenesis of depression. Consequently, targeted reactive oxygen species (ROS) elimination is regarded as a promising strategy for efficient depression therapy. In addition, insufficient brain drug delivery is the main obstacle to depression therapy owing to the presence of the blood-brain barrier (BBB). To achieve the goals of bypassing the BBB and promoting antioxidant therapy for depression, a broad-spectrum ROS scavenging NPs was rationally designed through a nasal-brain pathway developed for combined ROS scavenging and brain drug delivery. A hexa-arginine (R6) modified ROS-responsive dextran (DEX) derivate was synthesized for antidepressant olanzapine (Olz) and H2 donor amino borane (AB) loading to prepare Olz/RDPA nanoparticles (NPs). Subsequently, the NPs were dispersed into a thermoresponsive hydrogel system based on poloxamer. In vitro and in vivo results demonstrated that Olz/RDPA in situ thermoresponsive hydrogel system could effectively deliver NPs to the brain via the nasal-brain pathway and alleviate depression-like behaviors through combined ROS depletion and inhibition of 5-HT dysfunction of the oxidative stress-induced. The proposed ROS-scavenging nanotherapeutic would open a new window for depression treatment. STATEMENT OF SIGNIFICANCE: ROS is an innovative therapeutic target involving the pathology of depression whereas targeted delivery of ROS scavenging has not been achieved yet. In the current study, ROS-responsive nanoparticles (Olz/RDPA NPs) were prepared and dispersed in a thermosensitive hydrogel for delivery through the nasal-brain pathway for the treatment of depression. Sufficient ROS depletion and improvement of delivery capacity by the nasal-brain pathway effectively could reverse oxidative stress and alleviate depressive-like behavior. Collectively, these nanoparticles may represent a promising strategy for the treatment of depression.

Triple Function of Amelogenin Peptide-Chitosan Hydrogel for Dentin Repair

Biomimetic strategies like peptide-guided collagen mineralization promise to enhance the effectiveness of dentin remineralization. We recently reported that rationally designed amelogenin-derived peptides P26 and P32 promoted apatite nucleation, mineralized collagen, and showed potential in enamel regrowth and dentin remineralization. To facilitate the clinical application of amelogenin-derived peptides and to uncover their effectiveness in repairing dentin, we have now implemented a chitosan (CS) hydrogel for peptide delivery and have investigated the effects of P26-CS and P32-CS hydrogels on dentin remineralization using 2 in situ experimental models that exhibited different levels of demineralization. The efficacy of the peptide-CS hydrogels in dentin repair was evaluated by characterizing the microstructure, mineral density, mineral phase, and nanomechanical properties of the remineralized samples. The new strategy of atomic force microscopy PeakForce quantitative nanomechanical mapping was used for direct visualization and nanomechanical analysis of repaired dentin lesions across the lesion depth. Results from the 2 models indicated the potential triple functions of peptide-CS hydrogels for dentin repair: building a highly organized protective mineralized layer on dentin, occluding dentinal tubules by peptide-guided in situ mineralization, and promoting biomimetic dentinal collagen remineralization. Importantly, peptides released from the CS hydrogel could diffuse into the dentinal matrix and penetrate the dentinal tubules, leading to both surface and subsurface remineralization and tubule occlusion. Given our previous findings on peptide-CS hydrogels’ potential for remineralizing enamel, we see further promise for hydrogels to treat tooth defects involving multiple hard tissues, as in the case of noncarious cervical lesions.

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.

Recent Advances in the Impact of Antibiotic and Antioxidant Multifunctional Hydrogel on Diabetic Wounds Healing

Abstract: Hyperglycemia is a metabolic illness characterized by diabetes mellitus. Chronic hyperglycemia can lead to infection, production of more reactive oxygen species, chronic inflammation, and impaired angiogenesis, thus increasing the wound’s healing time. As the diabetic wound healing process is a more complex pathology, the demand to develop a topical application has emerged. This review focuses on the diabetic wound, wound healing, and the factors that influence diabetic wound healing. It also highlights the impact of combination delivery of antibiotics and antioxidants loaded with multifunctional hydrogel on diabetic wound healing. Due to the immense financial strain caused by this pathology, there is a need for other effective novel methods for wound healing. Therefore, multifunctional hydrogels, which are effective and have been used mainly as a carrier system for diabetic wound treatment, have been studied. Hence, the application of antibiotics and antioxidants loaded with multifunctional hydrogel in treating diabetic wounds is reviewed. Hydrogels present a significant theoretical reference for diabetic wound healing.