Acid-based Hydrogel Research Articles

Hyaluronic Acid-Based 3D Bioprinted Hydrogel Structure for Directed Axonal Guidance and Modeling Innervation In Vitro.

Neurons form predefined connections and innervate target tissues through elongating axons, which are crucial for the development, maturation, and function of these tissues. However, innervation is often overlooked in tissue engineering (TE) applications. Here, multimaterial 3D bioprinting is used to develop a novel 3D axonal guidance structure in vitro. The approach uses the stiffness difference of acellular hyaluronic acid-based bioink printed as two alternating, parallel-aligned filaments. The structure has soft passages incorporated with guidance cues for axonal elongation while the stiff bioink acts as a structural support and contact guidance. The mechanical properties and viscosity differences of the bioinks are confirmed. Additionally, human pluripotent stem cell (hPSC) -derived neurons form a 3D neuronal network in the softer bioink supplemented with guidance cues whereas the stiffer restricts the network formation. Successful 3D multimaterial bioprinting of the axonal structure enables complete innervation by peripheral neurons via soft passages within 14 days of culture. This model provides a novel, stable, and long-term platform for studies of 3D innervation and axonal dynamics in health and disease.

Self-Healing Hyaluronic Acid-based Hydrogel with miRNA140-5p Loaded MON-PEI Nanoparticles for Chondrocyte Regeneration: Schiff Base Self-Assembly Approach.

Articular cartilage defects present a significant therapeutic challenge due to the inherent avascular and aneural characteristics of cartilage tissue. Gene therapy has emerged as a promising strategy for cartilage regeneration, particularly through the use of functional RNA and biomaterial-assisted frameworks. In this study, an innovative gene-activated self-healing hydrogel is developed and fabricated for the controlled release of miR140-5p, a key regulator of cartilage regeneration. The hydrogel, crosslinked via UV radiation, is composed of aminated hyaluronic acid and a modified photosensitizer (NB). To enhance the scaffold's structural integrity and gene delivery efficiency, mineralized silk fibroin and miR140-5p-loaded MON-PEI nanoparticles are incorporated. These findings demonstrate that this novel hydrogel (miR140-5p-CaP@mSF-HA-NB) effectively encapsulates and releases miR140-5p, exhibits excellent biocompatibility, and promotes enhanced cartilage regeneration in both in vitro and in vivo models. Therefore, this gene-activated hydrogel holds significant potential for clinical applications in the treatment of articular cartilage defects.

IOP Reduction in Nonhuman Primates by Microneedle Injection of Drug-Free Hydrogel to Expand the Suprachoroidal Space.

Expansion of the suprachoroidal space (SCS) by a hydrogel injection has been shown to reduce intraocular pressure (IOP) in rabbits as a potential treatment for ocular hypertension in glaucoma. Here, we evaluate the safety and efficacy of this approach in hypertensive and normotensive eyes in nonhuman primates. A microneedle was used to inject a hyaluronic acid-based hydrogel or saline solution (control) into the SCS of cynomolgus monkey eyes that were either normotensive (n = 7 experimental; n = 2 control eyes) or had induced ocular hypertension (n = 6 experimental; n = 3 control eyes). IOP and the degree of SCS expansion were monitored over time by tonometry and ultrasound biomicroscopy, respectively. Safety was evaluated through slit lamp, fundus, and histology examinations. In hypertensive eyes, SCS injection with hydrogel initially reduced IOP by 47.5 ± 16.7%, and IOP returned to baseline in 38 days. In normotensive eyes, hydrogel injection initially reduced IOP by 38.8 ± 8.1% and IOP gradually returned to baseline also in 39 days. Sham injections resulted in mild IOP reduction in hypertensive eyes and normotensive eyes. The hydrogel injections were well tolerated by clinical assessments. IOP was reduced in nonhuman primates for over one month by sustained SCS expansion. This procedure was safe and simple to perform. These data confirm the translational potential of this treatment method. Further optimization of the hydrogel may provide longer durations of IOP reduction. A microneedle injection of hydrogel into the suprachoroidal space may provide a non-surgical, non-pharmacologic treatment for ocular hypertension in glaucoma patients.

Novel ophthalmic hyaluronic acid-hydrogel with curcumin nanoparticles for enhanced healing of ulcerative keratitis in rabbit model

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with β-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with β-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with β-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage.

Nanozyme-enhanced injectable hyaluronic acid-based hydrogel for the treatment of osteoarthritis

The progression of osteoarthritis (OA) is dramatically accelerated by excessive reactive oxygen species (ROS)-induced apoptosis of chondrocytes and the inflammatory response of synovial macrophages. In this study, we developed an injectable hydrogel with a catalase-mimicking nanozyme activity as a therapeutic agent for OA. In vitro experiments confirmed that the HA and peroxide-mimetic nanoenzyme-enhanced hydrogel, containing ε-polylysine/Mn1.8Co1.2O4 (ε-PLE/MnCoO) nanoparticles, continuously eliminated ROS and inflammatory cytokines while promoting the polarization of inflammatory macrophages (M1 phenotype) towards anti-inflammatory macrophages (M2 phenotype) in dysfunctional microenvironments. When used for intraarticular injections in OA models, the nanoenzyme-enhanced hydrogel effectively reduced oxidative stress by scavenging ROS and regulating the immune microenvironment. It resulted in a subsequent reduction in the expression of inflammatory factors, including MMP-13, TNF-α, IL-1β, and iNOS in both the synovium and joint fluid. Moreover, cartilage repair was enhanced by the promotion of COL-2 and SOX-9 expression in the cartilage tissue, whereas osteophyte formation in OA was reduced. This study introduced an innovative treatment strategy for the clinical management of OA, demonstrating its significant potential for application in treating OA.

Tea polyphenol nano-crosslinked dynamical hyaluronic acid-based hydrogel for diabetic wound healing

Diabetic wound healing remains a significant clinical challenge for the complex wound microenvironment characterized by oxidative stress, inflammation, and bacterial infection. To address these challenges, we present a novel hydrogel incorporates tea polyphenol-stabilized silver nanoparticles (TP@Ag NPs) into a dynamic hyaluronic acid-phenylboronic acid network crosslinked via borate ester bonds. This design leverages the inherent biocompatibility and biodegradability of hyaluronic acid alongside the antioxidant, anti-inflammatory, and antibacterial properties of tea polyphenols and silver nanoparticles. The HP-TP@Ag hydrogel exhibited glucose-responsive degradation and TP@Ag NPs release, enabling targeted delivery within the diabetic wound microenvironment. In vitro assays demonstrated the hydrogel's potent antioxidant activity, effectively scavenging ROS and protecting both HaCaT and RAW264.7 cells from oxidative stress. Furthermore, the HP-TP@Ag hydrogel significantly suppressed the production of pro-inflammatory cytokines and exhibited robust antibacterial activity against both E. coli and S. aureus. In vivo studies using a diabetic mouse model revealed accelerated wound closure, reduced inflammation, enhanced collagen deposition, and promoted angiogenesis and tissue remodeling in HP-TP@Ag hydrogel-treated wounds. These findings highlight the promise of HP-TP@Ag hydrogel as an advanced wound dressing for effective diabetic wound management, offering a synergistic approach to overcome the multifaceted challenges associated with this complex condition.

Itaconic Acid-Based Hydrogels with Flame Retardancy and High-Temperature Resistance via Vat Photopolymerization 3D Printing

Itaconic Acid-Based Hydrogels with Flame Retardancy and High-Temperature Resistance via Vat Photopolymerization 3D Printing

Rapidly Gelled Lipoic Acid-Based Supramolecular Hydrogel for 3D Printing of Adhesive Bandage.

Developing a strongly adhesive, easily removable, and robust bandage is valuable in trauma emergencies. Poly(lipoic acid) (PLA)-based adhesives with good mechanical properties have been well-developed through a thermal ring-opening polymerization (ROP) method that is easiness. However, the additive manufacturing of PLA-based adhesives remains a challenge. Herein, α-lipoic acid (LA) and trometamol (Tris) are found to rapidly form a supramolecular hydrogel at room temperature with injectability and 3D printing potential. Meanwhile, the synthesized LA-grafted hyaluronic acid and cellulose nanocrystals are involved not only to optimize the extrusion of 3D printing but also to effectively promote fidelity and prevent the inverse closed-loop depolymerization of PLA in water. The hydrogel bandage exhibits strong adhesion to skin while it can be removed with no residue by water flushing, showing protection to neo-tissue during dressing replacement. The in vivo application of the hydrogel bandage significantly promoted wound healing by closing the wound, forming a physical barrier, and providing an anti-inflammatory effect, showing great potential in future clinical applications.

Phytic acid-based super antifreeze multifunctional conductive hydrogel for human motion monitoring and energy harvesting devices

Conductive hydrogels have broad application prospects in the field of self-powered sensors and energy harvesting devices due to their good electrical conductivity and flexibility. However, at low temperatures, conductive hydrogels are usually frozen, resulting in problems such as poor electrical conductivity and flexibility, which seriously hinder the application of these fields. To address these challenges, phytic acid (PA) was employed as the crosslinker and antifreezing agent in this study. Polyvinyl alcohol (PVA), 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), chitosan (CS), and PA were used as raw materials to successfully synthesize PVA/AMPS/CS/PA (PACP) multifunctional conductive hydrogels with outstanding antifreeze and water retention properties (freezing point below −80 °C, 30-day water loss rate of 3.5%). In addition, PACP hydrogels exhibit exceptional electrical conductivity of up to 9.4 S/m, along with antibacterial and biocompatible properties, enabling their utilization as wearable sensors on human skin tissue. Notably, the PACP hydrogel-based triboelectric nanogenerator (PACP-TENG) excels in accurately monitoring human motion and powering small electronic devices, facilitating remote control of small light switches. The resulting open circuit voltage is as high as 314 V at 25 °C and about 110 V at low temperature. Therefore, PACP hydrogels with excellent properties are expected to expand their applications in these fields.

Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.

Electro-responsive superabsorbent hydrogel based on carboxymethyl cellulose as a draw agent for forward osmosis desalination

To explore a simple and energy-efficient approach to regenerate draw agent is a key challenge for forward osmosis (FO) desalination. Electro-responsive hydrogels have attracted great attention due to their reversible swelling-shrinking behaviors under an electric stimulus. However, the developed electro-sensitive hydrogels based on 2-acrylamido-2-methyl-l-propanesulfonic acid (AMPS) so far exhibit low reusability due to their unstable electro-sensitive properties and poor degradability with potential environmental impact. This study explored the use of an electro-responsive superabsorbent hydrogel as a draw agent by grafting acrylic acid (AA) and acrylamide (AM) onto sodium carboxymethyl cellulose (CMC). The grafted hydrogel’s morphology and structure were investigated by FTIR and SEM. The swelling behaviors and deswelling properties in an electrode contact system were examined. The swelling kinetics of the hydrogel could be well described by the Schott's pseudo-second-order model with a theoretical swelling ratio of 452.5 g/g. The grafted hydrogel exhibited stable electro-sensitive characteristics with a decrease of 7.3 % in the equilibrium swelling ratio after undergoing three cycles of deswelling and swelling. During the FO test, the dry hydrogel particles produced a water flux of 1.55 L·m−2·h−1 within the first hour, surpassing the performance of other carboxylic acid-based hydrogels used as draw agents. Significantly, it exhibited encouraging water recovery capabilities in the five recycling FO processes, retaining around 84 % of its initial water recovery ratio after 40 min of exposure to a voltage of 15 V. This indicated that the grafted hydrogel could be considered as an effective and sustainable draw agent for FO desalination.

Injectable Salecan/hyaluronic acid-based hydrogels with antibacterial, rapid self-healing, pH-responsive and controllable drug release capability for infected wound repair

Designing materials for wound dressings with superior therapeutic benefits, self-healing and injectable characteristics is important in clinical practice. Herein, a new self-healing injectable hydrogel was prepared via thermal treatment and dynamic Schiff base reaction by mixing oxidized hyaluronic acid (OHA) and hydrazided Salecan (Sal-ADH). The versatility of the wound dressing was confirmed by studying the inherent rheological properties, high swelling rate, sustained-release behavior of the drug, pH/hyaluronidase-dependent biodegradation, in vitro antimicrobial as well as in vivo wound healing performance. The presence of the antimicrobial drug polyhexamethylene biguanide (PHMB) conferred good antimicrobial properties to the Sal-ADH/OHA/PHMB (SOP) hydrogel, which could effectively prevent wound infection (the width of the inhibition circle of SOP-0.20 hydrogel was 4.97 mm, 5.93 mm for Staphylococcus aureus and Escherichia coli, respectively). The findings suggested that SOP hydrogel exhibited remarkable self-healing and injectability properties, as well as excellent hemostasis and biocompatibility. In vivo experiments indicated that the application of SOP hydrogels would obviously accelerate wound healing and attenuate the inflammatory response while increasing collagen deposition and angiogenesis. Altogether, antibacterial SOP hydrogels with moderate mechanical properties, pH-responsive release, excellent injectability, exceptional self-healing ability and anti-inflammatory effects could expand potential applications of injectable hydrogels in the biomedical field.

“All-in-one” tea polyphenol-modified injectable hyaluronic acid-based hydrogel for diabetic wound healing

Refractory diabetic wounds are a devastating and rapidly growing clinical problem, which is associated with high incidence rates, mortality, and recurrence rates. Therapeutic angiogenesis in wound tissues is essential to the healing of diabetic wounds. However, the presence of excessive oxidative stress in diabetic wounds hinders angiogenesis, and conventional anti-oxidative approaches are inefficient to compensate for the systematically impaired angiogenesis. Here, a multifunctional supramolecular hyaluronic acid hydrogel dressing for diabetic wounds is successfully designed and constructed (GHPM). The GHPM hydrogel features outstanding properties, including excellent tissue adhesion, antibacterial ability, conductivity, and antioxidant properties. Based on the dynamic crosslinking structure, the GHPM hydrogel also presents adequate injectable and self-healing capabilities, which play a vital role in covering irregular or deep wounds. Additionally, diabetic wounds treated with GHPM hydrogel showed a significant acceleration of wound closure by preventing wound infection, reducing oxidative stress, and accelerating collagen deposition. More interestingly, the combination of electrical stimulation and GHPM hydrogel can effectively promote angiogenesis and neurogenesis, further accelerating diabetic wound healing in an all-around way. This advanced collaborative strategy opens a new avenue in treating diabetic wounds.

Stable and antibacterial tannic acid-based covalent polymeric hydrogel for highly selective Pb2+ recovery from lead-acid battery industrial wastewater

The resource of trace lead (Pb2+) from wastewater bearing intricate components is imperative for sustainable progression of the lead-acid battery industry. Herein, we fabricated a tannic acid-based covalent polymeric hydrogel (TA@PMAM) with antimicrobial properties and stability via facile Michael addition reaction. The incorporation of tannic acid (TA) through robust covalent bond leads to a stable porous 3D covalent polymer network with almost no loss of mechanical properties even after 20 compression cycles. Batch adsorption experiments of TA@PMAM revealed an extraordinary adsorption capacity of Pb2+(Qe =196.6 mg/g), achieving 87.2 % of Pb2+ adsorption within the first 5 min owing to porous structure, numerous adsorption sites and good hydrophilicity. Moreover, TA@PMAM demonstrated a strong affinity for Pb2+ in the presence of the interfere metal ions (Cu2+, Co2+, Mn2+etc.) due to the carbonyl and phenolic hydroxyl that can specifically pair with Pb2+. Stable adsorption properties of TA@PMAM were confirmed in fixed bed column adsorption experiment using lead-acid batteries wastewater, retaining 79.56 % of initial adsorption capacity even after 10 times’ reuse. Besides, TA@PMAM possesses a broad spectrum of antimicrobial properties. This study sheds novel light on the design and fabrication of adsorbent, which holds great potential for commercialization in recovering lead from battery industrial wastewater.

Doxorubicin-loaded liposome-like particles embedded in chitosan/hyaluronic acid-based hydrogels as a controlled drug release model for local treatment of glioblastoma

Glioblastoma (GBM) resection and medication treatment are limited, and local drug therapies are required. This study aims to create a hybrid system comprising liposome-like particles (LLP-DOX) encapsulated in chitosan/hyaluronic acid/polyethyleneimine (CHI/HA/PEI) hydrogels, enabling controlled local delivery of doxorubicin (DOX) into the resection cavity for treating GBM. CHI/HA/PEI hydrogels were characterized morphologically, physically, chemically, mechanically, and thermally. Findings revealed a high network and compact micro-network structure, along with enhanced physical and thermal stability compared to CHI/HA hydrogels. Simultaneously, drug release from CHI/HA/PEI/LLP-DOX hydrogels was assessed, revealing continuous and controlled release up to the 148th hour, with no significant burst release. Cell studies showed that CHI/HA/PEI hydrogels are biocompatible with low genotoxicity. Additionally, LLP-DOX-loaded CHI/HA/PEI hydrogels significantly decreased cell viability and gene expression levels compared to LLP-DOX alone. It was also observed that the viability of GBM spheroids decreased over time when interacting with CHI/HA/PEI/LLP-DOX hydrogels, accompanied by a reduction in total surface area and an increase in apoptotic tendencies. In this study, we hypothesized that creating a hybrid drug delivery system by encapsulating DOX-loaded LLPs within a CHI/HA/PEI hydrogel matrix could achieve sustained drug release, improve anticancer efficacy via localized treatment, and effectively mitigate GBM progression for 3D microtissues.

A Critical Sojourn of Hyaluronic Acid-based Hydrogels in the Wound Healing Process: Current Advances and Future Prospects

Abstract: "Hyaluronic acid (HA), a non-sulfated glycosaminoglycan (GAG), is a significant component of the epidermal extracellular matrix (ECM). It plays multiple roles in the inflammatory response, cell adhesion, migration, proliferation, differentiation, angiogenesis, and tissue regeneration. Due to its inherent characteristics, including non-immunoreactivity, exceptional biocompatibility, biodegradability, native biofunctionality, hydrophilicity, and non-immunoreactivity, HA has found applications in the production of wound dressings. HA's synergistic role in enhancing deeper penetration into chronic wounds and its biofunctional properties in the healing process have been harnessed. HA-based wound dressings, often incorporating biomolecules or drugs to improve the dressing's biochemical performance during wound healing, have been developed. In this review, we explore the current state of knowledge regarding hydrogels based on HA, focusing on their biofunctional properties and delivery mechanisms. We present the latest developments in the research and development of HA-based hydrogels for the treatment of skin wounds."

Spider Silk-Inspired Hyaluronic Acid-Based Hydrogels with Superior Self-Healing Capability and Enhanced Strength.

Hyaluronic acid hydrogels are promising materials for diverse applications, yet their potential is hampered by limitations such as low self-healing efficiency and insufficient mechanical strength. Inspired by the heterogeneous structures of spider silk, we introduce a novel dual dynamically crosslinked network hydrogel. This hydrogel comprises an acylhydrazone-crosslinked network, utilizing aldehyde hyaluronic acid (AHA) and 3,3'-dithiobis (propionohydrazide) (DTP) as a first network, and a secondary network formed by hydrogen bonds-crosslinked network between tannic acid (TA) and silk fibroin (SF) with β-sheet formation. The hydrogel exhibits exceptional self-healing ability due to the dynamic and reversible nature of Schiff base bonds, disulfide bonds, and hydrogen bonds, achieving complete healing within 5 minutes. Additionally, the spider silk-inspired heterogeneous structures enhance mechanical properties. Furthermore, the incorporation of TA provides enhanced adhesion, as well as remarkable antibacterial and antioxidant properties. This innovative hyaluronic acid-based hydrogel, inspired by spider silk, offers a promising avenue to fortify both the mechanical strength and self-healing capabilities of hydrogels, thus expanding opportunities for applications in tissue engineering and biomedicine.

A simple and universal approach for fabricating bioactive self-stacked hydrogels with enhanced therapeutic efficacy

Despite significant advancements in self-stacked hydrogels of herbal small molecules in recent years, the emergence of new pharmacological small molecule self-stacked hydrogel systems remains largely reliant on serendipity and painstaking efforts. To address this challenge, we proposed a ‘bioactive bivalent metal ions-coordinated pharmacological small molecules’ strategy. This approach enabled the preparation of triterpenoid betulinic acid-based self-stacked hydrogels with excellent injectable and self-healing properties via a simple two-step method. We extended this strategy to self-stacking hydrogels based on other pentacyclic triterpene small molecules, anthraquinone small molecules, flavonoid small molecules and synthetic steroid small molecules. This universal strategy is capable of extracting hydrophobic pharmacological small molecules to construct novel self-stacked biomaterials in a cost-effective, efficient, large-scale, and environmentally friendly manner. Importantly, we successfully synthesized Mg2+-coordinated betulinic acid (BA-Mg) self-stacked hydrogel at low concentrations in the bacterial cellulose (termed BC) hydrogel network, overcoming the mechanical limitations of self-stacked hydrogels for biomedical applications. The BA-Mg/BC hybrid hydrogel demonstrated exceptional biocompatibility, anti-inflammatory, and angiogenic properties, significantly accelerating the skin wound healing process through the synergistic pharmacological effects of Mg2+ and BA.

Programmable Release of Chemotherapeutics from Ferrocene-Based Injectable Hydrogels Slows Melanoma Growth.

Hydrogel-based injectable drug delivery systems provide temporally and spatially controlled drug release with reduced adverse effects on healthy tissues. Therefore, they represent a promising therapeutic option for unresectable solid tumor entities. In this study, a peptide-starPEG/hyaluronic acid-based physical hydrogel is modified with ferrocene to provide a programmable drug release orchestrated by matrix-drug interaction and local reactive oxygen species (ROS). The injectable ROS-responsive hydrogel (hiROSponse) exhibits adequate biocompatibility and biodegradability, which are important for clinical applications. HiROSponse is loaded with the two cytostatic drugs (hiROSponsedox/ptx) doxorubicin (dox) and paclitaxel (ptx). Dox is a hydrophilic compound and its release is mainly controlled by Fickian diffusion, while the hydrophobic interactions between ptx and ferrocene can control its release and thus be regulated by the oxidation of ferrocene to the more hydrophilic state of ferrocenium. In a syngeneic malignant melanoma-bearing mouse model, hiROSponsedox/ptx slows tumor growth without causing adverse side effects and doubles the relative survival probability. Programmable release is further demonstrated in a tumor model with a low physiological ROS level, where dox release, low dose local irradiation, and the resulting ROS-triggered ptx release lead to tumor growth inhibition and increased survival.

PH-sensitive semi-interpenetrating network of microcrystalline cellulose and methacrylic acid hydrogel for the oral delivery of insulin

Insulin is commonly administered to diabetic patients subcutaneously and has shown poor patient compliance. Due to this, research has been carried out extensively to find molecules that could deliver insulin orally. In this context, a new type of pH-responsive hydrogel, composed of microcrystalline cellulose and methacrylic acid-based hydrogels, has been developed and studied for the oral delivery of insulin. These hydrogels were prepared by free radical polymerization using potassium persulphate as initiator and N, N’-methylenebisacrylamide as a cross-linker. These pH-sensitive hydrogels showed swelling in distilled water as high as 5800 %. The hydrogels were investigated for swelling in saline and glucose solutions, and pH sensitivity was confirmed by swelling in solutions of different pH. The morphological shape was established by SEM, and the structure was analyzed by FTIR. Thermal degradation was investigated by TGA. In vitro release studies have confirmed pH sensitivity, showing lower insulin release at pH 1.2 than at pH 6.8. The encapsulation efficiency was determined to be 56.00 ± 0.04 %. It was further validated by in-vivo investigations for which insulin was loaded into hydrogels and administered orally to healthy and diabetic Wistar rats at 40 IU/kg, showing maximum hypoglycemic effect at 6 h, which was sustained for 24 h. In the stomach’s acidic environment, the gels remained unaffected due to the formation of intermolecular polymer complexes. Insulin remained in the gel and was protected from proteolytic degradation. Thus, pH-responsive methacrylic acid-based hydrogels are promising for biomedical applications, especially oral drug delivery.