Hydrogel Drug Delivery System Research Articles

Dual-sensitive drug-loaded hydrogel system for local inhibition of post-surgical glioma recurrence

Local treatment after resection to inhibit glioma recurrence is thought to able to meet the real medical needs. However, the only clinically approved local glioma treatment-wafer containing bis(2-chloroethyl) nitrosourea (BCNU) showed very limited effects. Herein, in order to inhibit tumor recurrence with prolonged and synergistic therapeutic effect of drugs after tumor resection, an in situ dual-sensitive hydrogel drug delivery system loaded with two synergistic chemo-drugs BCNU and temozolomide (TMZ) was developed. The thermosensitive hydrogel was loaded with reactive oxygen species (ROS)-sensitive poly (lactic-co-glycolic) acid nanoparticles (NPs) encapsulating both BCNU and TMZ and also free BCNU and TMZ. The in vitro synergistic effect of BCNU and TMZ and in vivo presence of ROS at the residual tumor site were confirmed. The prepared ROS-sensitive NPs and thermosensitive hydrogel, as well as the long-term release behavior of drugs and NPs, were fully characterized both in vitro and in vivo. After >90% glioblastoma resection, the dual-sensitive hydrogel drug delivery system was injected into the resection cavity. The median survival time of the experimental group reached 65days which was twice as long as the Resection only group, implying that this in situ drug delivery system effectively inhibited tumor recurrence. Overall, this study provides new ideas and strategies for the inhibition of postoperative glioma recurrence.

Responsive Hydrogels Based on Triggered Click Reactions for Liver Cancer.

Globally, liver cancer, which is one of the major cancers worldwide, has attracted the growing attention of technological researchers for its high mortality and limited treatment options. Hydrogels are soft 3D network materials containing a large number of hydrophilic monomers. By adding moieties such as nitrobenzyl groups to the network structure of a cross-linked nanocomposite hydrogel, the click reaction improves drug-release efficiency in vivo, which improves the survival rate and prolongs the survival time of liver cancer patients. The application of a nanocomposite hydrogel drug delivery system can not only enrich the drug concentration at the tumor site for a long time but also effectively prevents the distant metastasis of residual tumor cells. At present, a large number of researches have been working toward the construction of responsive nanocomposite hydrogel drug delivery systems, but there are few comprehensive articles to systematically summarize these discoveries. Here, this systematic review summarizes the synthesis methods and related applications of nanocomposite responsive hydrogels with actions to external or internal physiological stimuli. With different physical or chemical stimuli, the structural unit rearrangement and the controlled release of drugs can be used for responsive drug delivery in different states.

A dual-responsive hyaluronic acid nanocomposite hydrogel drug delivery system for overcoming multiple drug resistance

Chemotherapy is restricted by efficient drug outflow due to the multiple drug resistance (MDR) in heterogenous nature of tumor. Herein, we present a dual-responsive hyaluronic acid (HA) nanocomposite hydrogel that can not only response to the tumor microenvironment but also enhance chemotherapy. This HA hydrogel consists of a core-shell SiO2 (GOD@SiO2-Arg) and mesoporous silica nanoparticles (MSNs) with doxorubicin (DOX) as the cargo (DOX@MSN). It could rapidly release the GOD@SiO2-Arg nanoparticles at the low pH tumor-specific environment due to the cleavage of imine bond. GOD@SiO2-Arg activated by over-expressed glutathione (GSH) in tumor cells releases GOD due to the cleavage of disulfide bonds, which could oxidize glucose to produce hydrogen peroxide (H2O2) for in situ NO generation via reaction between Arg and H2O2. The validity of this study might provide a method to modulate the tumor microenvironment for enhancing chemotherapy.

Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy.

Glaucoma is extensively treated with topical eye drops containing drugs. However, the retention time of the loaded drugs and the in vivo bioavailability of the drugs are highly influenced before reaching the targeted area sufficiently, due to physiological and anatomical barriers of the eye, such as rapid nasolacrimal drainage. Poor intraocular penetration and frequent administration may also cause ocular cytotoxicity. A novel approach to overcome these drawbacks is the use of injectable hydrogels administered intravitreously for sustained drug delivery to the target site. These injectable hydrogels are used as nanocarriers to intimately interact with specific diseased ocular tissues to increase the therapeutic efficacy and drug bioavailability of the anti-glaucomic drugs. The human eye is very delicate, and is sensitive to contact with any foreign body material. However, natural biopolymers are non-reactive, biocompatible, biodegradable, and lack immunogenic and inflammatory responses to the host whenever they are incorporated in drug delivery systems. These favorable biomaterial properties have made them widely applicable in biomedical applications, with minimal adversity. This review highlights the importance of using natural biopolymer-based intravitreal hydrogel drug delivery systems for glaucoma treatment over conventional methods.

Effect of bone-shaped nanotube-hydrogel drug delivery system for enhanced osseointegration.

Anodic titanium dioxide nanotubes (TNT) have a range of beneficial theranostic properties. However, a lack of effective osseointegration is a problem frequently associated with the titanium dental implant surface. Here, we investigated whether bone-shaped nanotube titanium implants could enhance osseointegration via promoting initial release of vascular endothelial growth factor 165 (VEGF165) and dual release of recombinant human bone morphogenetic protein-2 (rhBMP-2). Thus, we generated cylindrical-shaped nanotubes (TNT1) and bone-shaped nanotubes (TNT2) through voltage-varying and time-varying electrochemical anodization methods, respectively. Additionally, we prepared rhBMP-2-loaded cylindrical-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F1) and rhBMP-2-loaded bone-shaped nanotubes/VEGF165-loaded hydrogel (TNT-F2) drug delivery systems. We evaluated the characteristics and release kinetics of the drug delivery systems, and then analyzed the cytocompatibility and osteogenic differentiation of these specimens with mesenchymal stem cells (MSCs) in vitro. Finally, we utilized a rat femur defect model to test the bone formation capacity of nanotube-hydrogel drug delivery system in vivo. Among these different nanotubes structures, the bone-shaped one was the optimum structure for growth factor release.

A Technical Overview: Polymers for Wounds and Burns Dressing as Hydrogel Drug Delivery System

In the last years, health care professionals faced with an increasing number of patients suffering from wounds and burns difficult to treat and heal. During the wound healing process, the dressing protects the injury and contributes to the recovery of dermal and epidermal tissues. Because their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body, some natural polymers such as polysaccharides (alginates, chitin, chitosan, heparin, chondroitin), proteoglycans and proteins (collagen, gelatin, fibrin, keratin, silk fibroin, eggshell membrane) are extensively used in wounds and burns management. Obtained by electrospinning technique, some synthetic polymers like biomimetic extracellular matrix micro/nanoscale fibres based on polyglycolic acid, polylactic acid, polyacrylic acid, poly-ε-caprolactone, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, exhibit in vivo and in vitro wound healing properties and enhance re-epithelialization. They provide an optimal microenvironment for cell proliferation, migration and differentiation, due to their biocompatibility, biodegradability, peculiar structure and good mechanical properties. Thus, synthetic polymers are used also in regenerative medicine for cartilage, bone, vascular, nerve and ligament repair and restoration. Biocompatible with fibroblasts and keratinocytes, tissue engineered skin is indicated for regeneration and remodelling of human epidermis and wound healing improving the treatment of severe skin defects or partial-thickness burn injuries. This article offers an insight into several different types of polymeric materials clinically used in wound dressings and the events taking place at cellular level, which aid the process of healing, while the biomaterial dressing interacts with the body tissue.

Design of a new light curable starch-based hydrogel drug delivery system to improve the release rate of quercetin as a poorly water-soluble drug

In spite of quercetin advantages, its utilization as a cancer drug is confined due to its very low water solubility and bioavailability. Accordingly, we prepared a biodegradable starch-based hydrogel, using a new technique to control and improve quercetin release and bioavailability. For this purpose, the molecular structure of starch was modified by polyethylene glycol/acrylate and Fe3O4 nanoparticles were used to enhance mechanical properties of hydrogel. In order to prepare the final hydrogel drug carrier, the modified starch was directly mixed with quercetin and other additives in different ratios and cured under blue light. Synthesis confirmation and structural properties of the modified starch, silanized and pure Fe3O4 nanoparticles and final hydrogel were studied using 1H NMR, FT-IR, SEM, XRD, TGA, VSM and DLS analyses. We improved in vitro drug release to 56.62%, while the maximum release of quercetin from the starch-based hydrogel in our previous study was only 27% (Doosti et al., 2019).

In situ injectable hydrogel-loaded drugs induce anti-tumor immune responses in melanoma immunochemotherapy.

Melanoma is a highly aggressive tumor located in the skin, with limited traditional therapies. In order to reduce the side effects caused by traditional administration method and amplify the killing effect of immune system against tumor cells, an in situ injectable hydrogel drug delivery system is developed for the first time which co-delivers doxorubicin (Dox) and imiquimod (R837) for the synergistic therapy of melanoma. The mechanical properties and stability of the hydrogel are characterized and the optimal doses of hydrogel and drugs are also identified. As a result, the co-delivery system effectively suppresses melanoma growth and metastatic progression both in vitro and in vivo. Further studies show that the co-delivery system causes immunogenic cell death, activation of antigen presenting cells, comprising dendritic cells and M1 macrophages, and secretion of related cytokines consisted of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), subsequently with the activation of T lymphocytes and natural killer cells in spleen and tumor area. The co-delivery system also decreases the suppressive immune responses, including infiltration of M2 macrophages and secretion of interleukin-10 (IL-10), in vivo. Besides, other death modes are induced by the co-delivery system, including apoptosis and non-apoptotic cell death. In a word, this co-delivery system induces melanoma cell death directly and activates immune system for further tumor killing simultaneously, which shows probability for precise targeted tumor therapy.

Simultaneous Release of Aflibercept and Dexamethasone from an Ocular Drug Delivery System

Purpose Intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) are the current standard of care for patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). There is a growing subset of patients that does not respond to anti-VEGF monotherapy treatment. Some patients, however, do respond to combination therapy of corticosteroids and anti-VEGF. This treatment requires monthly/bimonthly injections of anti-VEGF and semi-annual injections of corticosteroid. A drug delivery system (DDS) that simultaneously releases multiple drugs could benefit these patients by reducing the number of injections. The purpose of this study was to characterize the simultaneous release of aflibercept and dexamethasone from a biodegradable microparticle- and nanoparticle-hydrogel DDS. Methods Dexamethasone-loaded nanoparticles and aflibercept-loaded microparticles were created using modified single- and double-emulsion techniques, respectively. Then, microparticles and nanoparticles were embedded into a thermoresponsive, biodegradable poly(ethylene glycol)-co-(L-lactic acid) diacrylate (PEG-PLLA-DA)-N-isopropylacrylamide (NIPAAm) hydrogel DDS. Drug release studies and characterization of DDS were conducted with varying doses of microparticles and nanoparticles. Results The combination aflibercept-loaded microparticle- and dexamethasone-loaded nanoparticle- hydrogel (Combo-DDS) achieved a total release time of 224 days. Small decreases were seen in swelling ratio and equilibrium water content for Combo-DDS compared to monotherapy aflibercept-loaded microparticle-hydrogel DDS (AFL-DDS) and monotherapy dexamethasone-loaded nanoparticle-hydrogel DDS (DEX-DDS). Bioactivity of aflibercept was maintained in Combo-DDS compared to AFL-DDS. Conclusions The Combo-DDS was able to extend and control the release of both aflibercept and dexamethasone simultaneously from a single DDS. This may eliminate the need for separate dosing regiments of anti-VEGF and corticosteroids for wet AMD patients.

Drug delivery system based on PVA and clay for potential treatment of COVID-19

Tremendous efforts are being made around the world to develop efficient ways to prevent/treat the novel β-coronavirus disease (COVID-19) caused by SARS-CoV-2. There are currently many studies and clinical trials (either based on computational predictions or clinical experiences), in progress, focusing on finding relevant protein targets and medications anti-COVID-19. In the present study, we report a hydrogel drug delivery system based on Laponite® RD (Lap) entrapped in a poly(vinyl alcohol) (PVA) matrix obtained by freezing/thawing method. The PVA/Lap hydrogels were characterized in terms of their morphological, rheological, and swelling properties. Moreover, in vitro drug delivery investigations were performed with a promising drug, Rifampicin (Rif). Rif is an antitubercular drug and was selected for this study in order to demonstrate its efficacy as an anti-COVID-19 repurposed drug. In vitro studies were supplemented by in silico molecular docking simulations of Rif capacity of inhibition against SARS-CoV-2 target protein 3-chymotrypsin-like protease (3CLpro). The results obtained in this study are encouraging and we propose the Rif loaded PVA/Lap hydrogels as promising drug delivery systems for COVID-19 treatment, promoting a synergistic therapeutic effect by dual targeting of viral 3CLpro and S proteins.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10965-022-02927-5.

An injectable thermosensitive hydrogel loaded with a theranostic nanoprobe for synergistic chemo-photothermal therapy for multidrug-resistant hepatocellular carcinoma.

Multi-drug resistance (MDR) is a complicated cellular defense mechanism for tumor cells to resist chemotherapy drugs, which is also the main cause of chemotherapy failure. In this study, a local injectable hydrogel delivery system was used to construct an on-demand sustained-release platform with the advantages of chemotherapy, photothermal therapy (PTT), and magnetic resonance imaging (MRI). It could achieve synergistic chemo-photothermal therapy and real-time evaluation of the therapeutic effects (via MRI) for MDR hepatocellular carcinoma (HCC). Furthermore, after a single administration, the prepared hydrogel with a theranostic nanoprobe could release the therapeutic agents on demand for up to 14 d. Firstly, doxorubicin (DOX) and gold-manganese oxide (Au-MnO) nanoparticles (NPs) were incorporated into liposome-based self-assembled micelles, then loaded into the thermosensitive hydrogel (F127) to form DOX@Au-MnO-L NPs/F127 hydrogel (DAML/H). The prepared NP complex showed a spherical morphology with a narrow size distribution. The prepared hydrogel drug delivery system had injectable properties and stable photothermal conversion. Both the DOX@Au-MnO-L NPs and DAML/H showed controlled drug release under near infrared (NIR) laser irradiation. The in vitro MRI studies indicated that the prepared DAML/H had a high relaxation rate (14.38 mM-1 s-1) and good MRI scanning sensitivity conditions. The in vitro and in vivo results suggested the synergistic chemo-photothermal therapy of DAML/H with NIR irradiation (808 nm, 1 W cm-2, 10 min) improved the antitumor efficacy for MDR HCC. The in vivo retention experiment of Au in tumors indicated that the prepared hydrogel drug delivery system (DAML/H) had a good ability to retain Au in the tumor for a long time (at least 14 d). The western blotting results revealed that DAML/H with laser treatment could effectively downregulate P-glycoprotein (P-gp), p53 and antiapoptotic protein (Bcl-2), whereas the expression level of proapoptotic protein (Bax) and caspase-3 were increased. Therefore, DAML/H could serve as a promising synergistic chemo-photothermal therapy for MDR HCC, and a single administration might achieve long-term (14 d), on-demand, sustained-release treatment of tumors.

Multiple Stimuli-Responsive MXene-Based Hydrogel as Intelligent Drug Delivery Carriers for Deep Chronic Wound Healing.

Chronic wound healing is an important and basic issue in medical and healthcare fields. Recently, stimuli-responsive hydrogel systems have emerged as promising drug delivery carriers for wound management. However, given to the limited therapeutic outcomes, new hydrogel systems for efficient wound treatment are urgently needed. Here, the development of a 2D MXene-based hydrogel system for highly efficient photo- and magnetic-responsive drug delivery oriented to deep chronic wounds repair is presented. The intelligent responsive MXene-based hydrogel drug delivery system is composed of MXene-wrapped magnetic colloids and poly(N-isopropyl acrylamide)-alginate dual-network hydrogels. It is demonstrated that the MXene-based hydrogel system exhibits multiple response capability and controllable drug delivery ability, which can reduce the toxic side effects of drugs and promote the wound healing process as well. Notably, the practical performance of the MXene-based hydrogel drug delivery system is demonstrated by applying it to the treatment of the full-thickness cutaneous wound and subcutaneous infected wound of the rat model, which indicates the great prospect in clinical wound healing and other related biomedical fields.

Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin.

The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydrogel drug delivery system (GelMA-DDS) to locally deliver the broad-spectrum antibiotic cefazolin for SSI prophylaxis and treatment. Antibiotic doses from 3 µg to 90 µg were loaded in photocrosslinked GelMA hydrogel discs with 5 to 15% w/v polymer concentration and drug encapsulation efficiencies, mechanical properties, crosslinking and release kinetics, as well as bacterial growth inhibition were assessed. Our results demonstrate that all GelMA groups supported excellent drug encapsulation efficiencies of up to 99%. Mechanical properties of the GelMA-DDS were highly tuneable and unaffected by the loading of small to medium doses of cefazolin. The diffusive and the proteolytic in vitro drug delivery of all investigated cefazolin doses was characterized by a burst release, and the delivered cefazolin amount was directly proportional to the encapsulated dose. Accelerated enzymatic degradation of the GelMA-DDS followed zero-order kinetics and was dependent on both the cefazolin dose and GelMA concentration (3–13 h). Finally, we demonstrate that cefazolin delivered from GelMA induced a dose-dependent antibacterial efficacy against S. aureus, in both a broth and a diffusive assay. The cefazolin-loaded GelMA-DDS presented here provides a highly tuneable and easy-to-use local delivery system for the prophylaxis and treatment of SSI.

Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System.

The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery system (DDS) using a computational model and a 3D model of the eye. Hydrogel DDSs loaded with vancomycin (VAN) were synthesized and release behavior was characterized in vitro. Four different compartmental and four COMSOL models of the eye were developed to describe transport into the vitreous originating from a DDS placed topically, in the subconjunctiva, subretinally, and intravitreally. The concentration of the simulated DDS was assumed to be the initial concentration of the hydrogel DDS. The simulation was executed over 1500 and 100 h for the compartmental and COMSOL models, respectively. Based on the MATLAB model, topical, subconjunctival, subretinal and vitreous administration took most (~500 h to least (0 h) amount of time to reach peak concentrations in the vitreous, respectively. All routes successfully achieved therapeutic levels of drug (0.007 mg/mL) in the vitreous. These models predict the relative build-up of drug in the vitreous following DDS administration in four different points of origin in the eye. Our model may eventually be used to explore the minimum loading dose of drug required in our DDS leading to reduced drug use and waste.

Alginate hydrogels functionalized with β-cyclodextrin as a local paclitaxel delivery system.

Modification of drug delivery materials with beta-cyclodextrins (β-CyD) is known to increase solubility of poorly water-soluble drugs, protect drugs from degradation and sustain release. In this study, we developed a hydrogel drug delivery system for local paclitaxel delivery using the natural polysaccharide alginate functionalized with β-CyD-moieties. Paclitaxel was chosen due to its ability to form inclusion complexes with cyclodextrins. The rheological and mechanical properties of the prepared hydrogels were characterized, as well as in vitro release of the paclitaxel and in vitro activity on PC-3 prostate cancer cells. Introduction of β-CyD-moieties into the hydrogel reduces the mechanical properties of the gels compared to nonmodified gels. However, gelation kinetics were not markedly different. Furthermore, the β-CyD-modified alginate helped to reduce undesired crystallization of the paclitaxel in the gel and facilitated paclitaxel diffusion out of the gel network. Remarkably, the β-CyD grafted alginate showed increased capacity to complex paclitaxel compared to free HPβ-CyD. Release of both paclitaxel and degradation products were measured from the gels and were shown to have cytotoxic effects on the PC-3 cells. The results indicate that functionalized alginate with β-CyDs has potential as a material for drug delivery systems.

TN HYDROGELS AS A POTENTIAL ANTI-INFLAMMATORY DRUG DELIVERY SYSTEM TARGETED TO OSTEOARTHRITIC KNEES

Arthritis affects 26.3% of adults and approximately 50,000 children in the United States [1]. Hydrogel drug-delivery systems have been considered as a viable option for drug delivery to arthritic articular cartilage in the knee. To determine physiologically relevant loading, a Qualisys motion capture system was used to analyze the gait of college-aged females as they took several steps on a flat surface, then stepped onto a force plate. The motion capture and force plate data was used to determine maximum force exerted on the knee during normal gait. Three different alginate-based hydrogels, where the superior one had a triple interpenetrating graphene oxide network (TN hydrogels), were investigated for use as an antiinflammatory drug delivery system in a human knee joint. Physiologically relevant cyclic loading was performed to ensure that the TN hydrogel could withstand the force exerted in the knee. The TN hydrogel experienced a change in energy of 50% after cyclic loading (10.6 ± 15.0 Pa) and survived high stresses of 4 kPa, which is 80 magnitudes larger than observable gait forces as measured in this study. From a mechanical perspective, TN hydrogel appears to be mechanically viable for arthritis drug delivery. In addition, based on calculations and Flory-Rehner equations, the pore size of the TN hydrogel is adequate for encapsulating most NSAIDs, which have a molecule size ≤ 5μm.

Nanocomposite hydrogels for melanoma skin cancer care and treatment: In-vitro drug delivery, drug release kinetics and anti-cancer activities

Malignant melanoma is a lethal human skin cancer that is not easily treatable through traditional medicines, surgeries, and therapies. Millions of cases are recorded annually to cure physiological skin defects by chemotherapy that causes several adverse effects and challenges. Moreover, pathogenic infections might aggravate infection with subsequent ulceration or cutaneous melanoma. Accordingly, we synthesized nanodrug by loading chemotherapeutic agent, Fluorouracil (5FU), onto the reduced graphene oxide (rGO). We then extracted arabinoxylan (ARX) from the husk of Plantago Ovata and functionalized it into carboxymethylarabinoxylan (CMARX) and loaded synthesized nanodrug. We have crosslinked CMARX/nanodrug with different amount of tetraethylorthosilicate (TEOS) to prepare nanocomposite hydrogel rGO-5FU-CMARX system for melanoma skin cancer care and treatment. These nanocomposite hydrogel systems rGO-5FU-CMARX have exhibited different physicochemical properties. These properties were analyzed through FTIR, SEM, water contact angle, swelling in different media (aqueous and PBS) and biodegradation in PBS media. The in-vitro activities, i.e., drug delivery via Franz diffusion, antibacterial against S. aureus and P. aeruginosa and the anticancer activities was performed against Uppsala 87 Malignant Glioma (U-87) cell lines. Moreover, rGO-5FU-CMARX nanocomposite hydrogels displayed different antimicrobial and anticancer activities based on different crosslinking. Hence, an inventive rGO-5FU-CMARX based nanocomposite hydrogel drug-delivery system was developed to treat malignant melanoma skin cancer after bacterial infections.

Injectable bio-responsive hydrogel for therapy of inflammation related eyelid diseases

Eyelid plays a vital role in protecting the eye from injury or infection. Inflammation related eyelid diseases, such as blepharitis, are the most common ocular disorders that affect human's vision and quality of life. Due to the physiological barriers and anatomical structures of the eye, the bioavailability of topical administrated therapeutics is typically less than 5%. Herein, we developed a bio-responsive hydrogel drug delivery system using a generally recognized as safe compound, triglycerol monostearate (TG-18), for in-situ eyelid injection with sustained therapeutics release. In vitro, drug release and disassembly time of Rosiglitazone loaded hydrogel (Rosi-hydrogel) were estimated in the presence or absence of MMP-9, respectively. Moreover, the disassembly of TG-18 hydrogel was evaluated with 9-month-old and 12-month-old mice in vivo. Owing to the bio-responsive nature of Rosi-hydrogel, the on-demand Rosiglitazone release is achieved in response to local enzymes. These findings are proved by further evaluation in the age-related meibomian gland dysfunction mice model, and the bio-responsive hydrogel is used as an in-situ injection to treat eyelid diseases. Taken together, the in-situ eyelid injection with sustained drug release opens a window for the therapy of inflammation related eyelid diseases.

Injectable liquid metal nanoflake hydrogel as a local therapeutic for enhanced postsurgical suppression of tumor recurrence

Despite the great progress achieved in nanomedicine, liquid metal (LM) nanodroplets have been mostly implemented as photo-agents for tumor phototherapy. However, in the rational design and construction of LM-based nanoplatforms for chemotherapy, limitations such as low drug-loading efficiency (LE), poor water stability, sterile and sensitive surface chemistry against ligand modification, and difficult morphology control remain to be addressed. Here, a local injectable LM-doxorubicin (LM-DOX) nanoflake-imbedded hydrogel with pH-triggered drug release is developed to achieve an enhanced therapeutic efficacy for the prevention of postoperative tumor relapse. With hyperbranched poly(amido amine) (HPAA) as the ligand, the obtained LM nanodroplets presented excellent aqueous stability and a unique flaky nanomorphology, and chemotherapeutics can be facilely conjugated via Schiff-base reaction as well. Compared to LM-based nanospheres or nanorods (LMNSs or LMNRs), LM nanoflakes (LMNFs) exhibited much higher DOX loading capacity of 63.5%. Further encapsulation of LMNF-DOX within Pluronic F-127 ([email protected]) was used to diminish burst drug release, achieve long-term antitumor effect, and minimize systemic toxicity. Finally, this nano-formulation was injected into the tumor resection cavity for local chemotherapy to remove the residual tumor, achieving enhanced therapeutic efficacy and biosafety than free drugs. Overall, LMNF-based hydrogel drug delivery system represents a promising candidate for postsurgical cancer treatment.

Hydrogels Based on Poly(Ether-Ester)s as Highly Controlled 5-Fluorouracil Delivery Systems-Synthesis and Characterization.

A novel and promising hydrogel drug delivery system (DDS) capable of releasing 5‑fluorouracil (5-FU) in a prolonged and controlled manner was obtained using ε‑caprolactone‑poly(ethylene glycol) (CL-PEG) or rac‑lactide-poly(ethylene glycol) (rac‑LA-PEG) copolymers. Copolymers were synthesized via the ring-opening polymerization (ROP) process of cyclic monomers, ε‑caprolactone (CL) or rac-lactide (rac-LA), in the presence of zirconium(IV) octoate (Zr(Oct)4) and poly(ethylene glycol) 200 (PEG 200) as catalyst and initiator, respectively. Obtained triblock copolymers were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques; the structure and tacticity of the macromolecules were determined. The relationship between the copolymer structure and the reaction conditions was evaluated. The optimal conditions were specified as 140 °C and 24 h. In the next step, CL-PEG and rac-LA-PEG copolymers were chemically crosslinked using hexamethylene diisocyanate (HDI). Selected hydrogels were subjected to in vitro antitumor drug release studies, and the release data were analyzed using zero-order, first-order, and Korsmeyer-Peppas mathematical models. Controlled and prolonged (up to 432 h) 5-FU release profiles were observed for all examined hydrogels with first-order or zero-order kinetics. The drug release mechanism was generally denoted as non-Fickian transport.