Sustained Release Research Articles

Efficient One-Pot Synthesis of Carboxymethyl Chitosan Hydrogel for Sustained Release of Ibuprofen and Sulfadiazine

Efficient One-Pot Synthesis of Carboxymethyl Chitosan Hydrogel for Sustained Release of Ibuprofen and Sulfadiazine

Harnessing Natural Pollen as Sustained-Release, Mucoadhesive, and Biosafe Drug Microcapsules for Intravesical Instillation in Bladder Cancer Treatment.

Intravesical instillation is essential for bladder cancer treatment, but current therapy suffers from brief drug retention and insufficient contact bladder contact. Nano- and micro-sized capsules-based drug delivery systems are expected to solve these problems, which, however, face challenges such as weak mucoadhesion, low biosafety, and processing complexity, limiting their scalable application. In this study, the power of plant pollen-derived microcapsules, sporopollenin exine capsules (SECs) is harnessed that are produced by sequentially defatting and acidolysis sunflower pollen, to passive load with pirarubicin and achieve biosafe and high-efficiency intravesical chemotherapy. SECs exhibit no significant toxic effects in vitro or in vivo. Taking advantage of its intrinsic microscale core-shell structure and spiny surface topography, convenient encapsulation is achieved with an efficiency of 45.3±1.43% and sustained release of the simulate drug, and strong adhesion to the bladder mucosa even after multiple urination, which reduces the instillation-maintenance time to just 20 min. Drugs encapsulated in SECs maintained higher concentrations in the bladder for up to 5 h compared to those without SECs. In a murine orthotopic bladder cancer model, SECs enhance the intravesical chemotherapy effect of pirorubicin (increased by 38%). The study introduces an innovative, naturally occurring drug carrier for advancing future intravesical instillation therapies.

Implantable Biomaterials for Cancer Immunotherapies

AbstractCancer immunotherapy has revolutionized cancer treatment by leveraging the immune system to target and eliminate tumor cells. Implantable biomaterials, such as hydrogels, sponges, scaffolds, implantable microdevice platforms, and macrobeads, offer localized and sustained release of immunomodulatory agents, improving the delivery of treatments such as immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapies like CAR‐T cells. This review examines the emerging role of these biomaterials in modulating the tumor microenvironment, enhancing immune cell recruitment, and reducing systemic side effects, positioning them as significant tools for treating solid tumors. Recent advances in material engineering are also discussed, including the integration of bioactive molecules and real‐time therapeutic adjustments based on patient‐specific immune responses, which offer new potential in personalized cancer treatments. However, challenges such as biocompatibility, high production costs, variability in patient response, and the necessity of surgical manipulations remain key obstacles. Nonetheless, ongoing research and technological advancements are steadily addressing these issues, paving the way for more effective and accessible cancer immunotherapies. Overall, this review highlights the promise of implantable biomaterials overcoming the current limitations of cancer immunotherapy and expanding the scope of effective, targeted cancer treatments.

Abstract A020: Liposomal topotecan with low-intensity focused ultrasound utilization to improve drug penetration with brain parenchyma in pediatric brain tumors

Abstract The blood-brain barrier (BBB) remains a significant obstacle in delivering effective chemotherapeutics to treat pediatric brain tumors, limiting drug penetration and reducing therapeutic outcomes. To overcome this challenge, we investigated the use of liposomal topotecan (TPT), encapsulated in a sonosensitive formulation, designed for controlled release triggered by low-intensity focused ultrasound (LIFU). In this study, we evaluated the in vitro efficacy of a sonosensitive liposomal topotecan formulation. The liposomal topotecan was created using remote loading with an ammonium sulfate gradient. TPT was loaded at a drug-to-lipid ratio of 1:10. The liposome was composed of hydrogenated soy PC, cholesterol, and DSPE-PEG2000. IC50 assay comparing free topotecan to the liposomal topotecan indicated that the cytoxicity of free TPT is lower than liposomal TPT indicating a sustained release of drug which would decrease long term toxicity. In addition, pharmcokinetic fluorescent quantification of liposomal topotecan showed linear increase in free drug (ug/uL) as liposomal TPT concentration is increased in brain homogenates. We hypothesize that tumor growth inhibition and overall survival would be significantly improved in mice receiving LIFU-mediated liposomal topotecan delivery. Our future work includes additional pharmokinetics with survival analysis in vivo with and without low intensity focused ultrasound. These results highlight the potential of combining liposomal drug formulations with focused ultrasound to overcome the challenges of BBB permeability, offering a promising therapeutic strategy for improving drug accumulation and survival outcomes in pediatric brain tumor models. Citation Format: Avani Mangoli, Sarah Kim, Kathryn Blethen, Angela Everhart, Sasha Nikiforov, Gerry Grant, Luke Avigliano. Liposomal topotecan with low-intensity focused ultrasound utilization to improve drug penetration with brain parenchyma in pediatric brain tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A020.

Self-Cascade API Nanozyme for Synergistic Anti-Inflammatory, Antioxidant, and Ferroptosis Modulation in the Treatment of Corneal Neovascularization.

Corneal neovascularization is a common pathological ocular change that can severely impairs vision, potentially leading to blindness. Although steroids and non-steroidal anti-inflammatory drugs are the primary treatments, their side effects, such as ocular hypertension, eye irritation, and corneal lysis, limit their widespread use. In the present study, an active pharmaceutical ingredient (API) nanozyme (PC-DS NE) is developed through the metal-organic coordination of ferrous sulfate with the anti-inflammatory agent diclofenac sodium and the natural antioxidant proanthocyanidin. PC-DS NE exhibited a spheroid morphology with a particle size of 39.7 ± 5.2 nm, and could achieve the short-term release of diclofenac sodium and sustained release of proanthocyanidin. Notably, the PC-DS NE possessed favorable biocompatibility, self-cascade redox regulation capacity, and significant anti-inflammatory activity. In corneal alkali burn experiments, PC-DS NE effectively inhibited corneal neovascularization by scavenging reactive oxygen species, inhibiting the expression of inflammatory cytokines and pro-angiogenic factors, and down-regulating ferroptosis. These synergistic effects highlighted the potential of PC-DS NE as a promising treatment for ocular inflammatory diseases.

Dual-Functionalized Injectable pH-Responsive Hydrogels Loaded with Magnesium Peroxide for the Treatment of Implant-Associated Infection.

Implant-associated infections frequently complicate orthopedic surgeries, resulting in challenging issues. The current therapy of antibiotic treatment and surgical debridement often leads to drug resistance and bone defect. The development of pH-responsive antimicrobial and pro-osteogenic materials is a promising approach to controlling infections and repairing infected bone defects, especially given the weakly acidic pH of the bacterial infection area. Solid peroxides have the potential to provide a sustained release of hydrogen peroxide (H2O2), rendering them applicable for antimicrobial purposes. Additionally, their chemical properties render them inherently responsive to pH. Here, we propose a novel GelBA/PVA/MgO2 hydrogel composed of gelatin (Gel), benzeneboronic acid (BA), poly(vinyl alcohol) (PVA), and magnesium peroxide (MgO2) with self-healing ability and pH-responsiveness. The borate ester bond formed between PVA and BA is a dynamic chemical bond with properties of dynamic formation and dissociation, making the hydrogel both self-healable and pH-responsive. Meanwhile, the addition of MgO2 improves the network structure of the hydrogel and gives the hydrogel the ability to perform sustained release of H2O2 and Mg2+. Experimentally, the GelBA/PVA/MgO2 hydrogel exhibits controlled and pH-dependent H2O2 and Mg2+ release, sustained over time at physiological pH (7.4) and significantly increased at infection pH (5.5). In vitro and in vivo outcomes revealed that this hydrogel is able to inhibit Staphylococcus aureus growth and accelerate bone regeneration, improving bone healing without cytotoxic effects on normal tissues. These findings suggest that the GelBA/PVA/MgO2 hydrogel is a unique and efficient approach for anti-infection and therapeutic implant-associated infections.

Peptide Hydrogel for Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 In Vitro

This study aimed to investigate the impact of varying the formulation of a specific peptide hydrogel (PepGel) on the release kinetics of rhBMP-2 in vitro. Three PepGel formulations were assessed: (1) 50% v/v (peptides volume/total volume) PepGel, where synthetic peptides were mixed with crosslinking reagents and rhBMP-2 solution; (2) 67% v/v PepGel; (3) 80% v/v PepGel. Each sample was loaded with 12 µg of rhBMP-2 and incubated in PBS. Released rhBMP-2 was quantified by ELISA at 1 h, 6 h, and 1, 2, 4, 7, 10, 14, and 21 days. To explore how PepGel formulations influence rhBMP-2 release, the gel porosities, swelling ratios, and mechanical properties of the three PepGel formulations were quantitatively analyzed. The results showed that rhBMP-2 encapsulated with 50% v/v PepGel exhibited a sustained release over the 21-day experiment, while the 67% and 80% v/v PepGels demonstrated significantly lower rhBMP-2 release rates compared to the 50% formulation after day 7. Higher histological porosity of PepGel was significantly correlated with increased rhBMP-2 release rates. Conversely, the swelling ratio and elastic modulus of the 50% v/v PepGel were significantly lower than that of the 67% and 80% v/v formulations. In conclusion, this study indicates that varying the formulation of crosslinked PepGel can control rhBMP-2 release rates in vitro by modulating gel porosity, swelling ratio, and mechanical properties. Encapsulation with 50% v/v PepGel offers a sustained rhBMP-2 release pattern in vitro; if replicated in vivo, this could mitigate the adverse effects associated with burst release of rhBMP-2 in clinical applications.

Boosting the Sustained Release Performance of Metronidazole and Ornidazole with MIL-53(Fe) Derived Spherical Porous Carbon.

Metal-organic framework (MOF) derived spherical porous carbon (SPC) has potential application value in the field of adsorption and sustained release of nitroimidazole drugs. This work used MIL-53(Fe) as a precursor and prepared spherical 3-aminophenol-formaldehyde resin containing MIL-53(Fe) crystals using the advanced Stöber method, followed by the successful preparation of MIL-53(Fe) derived SPC (MSPC) with a structure containing both micropores and mesopores through high-temperature carbonization. The effects of the doping amount of MIL-53(Fe) on the sphericity and particle size of MSPC were investigated. The drug uptake capacity and sustained release performances of MSPC for metronidazole (MNZ) and ornidazole (ONZ) were assessed through batch tests, along with an investigation into the impact of varying pH levels on the sustained release performances. The experimental findings revealed that the drug loading of MNZ and ONZ onto MSPC achieved 111 and 120 mg/g, respectively, with a sustained release time of up to 24 h. The drug loading process adhered to the Langmuir isotherm adsorption model and conformed to the pseudo-second-order kinetics model, whereas the sustained release mechanism was consistent with the Korsmeyer-Peppas model. Furthermore, cytotoxicity and cyclic drug loading experiments indicated that MSPC exhibited good biocompatibility and stability. Therefore, this study provides new ideas for the development of SPC drug carriers.

Synthesis and evaluation of drug-loaded silver nanoparticles as hemostatic agents to halt uncontrolled bleeding

Objective The aim of this research study was to formulate a cost-effective, stable, less toxic and more efficacious intravenous nanoformulation that could rapidly augment the process of hemostasis. Significance Silver nanoparticles (AgNPs) evoked platelet activation, whereas alum (AM) neutralized the plasma proteins, causing blood coagulation. Tranexamic acid (TA) inhibited fibrinolysis and stabilized the formed blood clot. Methods The nanoformulation (NF) was subjected to characterization techniques such as UV-Vis spectrophotometry, FTIR, XRD, TGA and DSC analysis, which elucidated successful drug conjugation. Results Zeta-sizing confirmed the particle size of NF to be 256.6 nm with 0.497 PDI and a zeta potential of + 9.24 mV. In-vitro release profile exhibited first-order kinetics, indicating sustained release, conferring sustained release of NF for 12 h. NF was hemocompatible at the tested doses, as its extent of hemolysis was < 0.8% and < 1%, following EU and FDA guidelines, respectively. Ex-vivo studies revealed that NF recorded the highest viscosity, i.e., 36.5 cP, and maximum mass of clotted blood, i.e., 17.4 mg, in comparison to other combinations. In-vivo studies indicated a 100-fold dose reduction, i.e. 0.1 mg/kg, compared to the marketed formulation, Transamin® i.e. 10 mg/kg. 10 folds dose reduction i.e. 1 mg/kg, exhibited more efficacious results than Transamin®, owing to the synergistic effect and nano-sizing of components. Conclusion A safe, cost-effective, and relatively less toxic hemostatic nanoparticles were formulated, that can be intravenously administered to halt bleeding within seconds.

Nanomedicine in the treatment of Alzheimer's disease: bypassing the blood-brain barrier with cutting-edge nanotechnology.

Alzheimer's disease (AD) remains a formidable challenge in the field of neurodegenerative disorders, necessitating innovative therapeutic strategies. Nanomedicine, leveraging nanomaterials, has emerged as a promising avenue for AD treatment, with a key emphasis on overcoming the blood-brain barrier (BBB) to enhance drug delivery efficiency. This review provides a comprehensive analysis of recent advancements in the application of nanomaterials for AD therapy, highlighting their unique properties and functions. The blood-brain barrier, a complex physiological barrier, poses a significant hurdle for traditional drug delivery to the brain. Nanomedicine addresses this challenge by utilizing various nanomaterials such as liposomes, polymeric nanoparticles, and metal nanoparticles. These nanocarriers enable improved drug bioavailability, sustained release, and targeted delivery to specific brain regions affected by AD pathology. The review discusses the diverse range of nanomaterials employed in AD treatment, exploring their capacity to encapsulate therapeutic agents, modulate drug release kinetics, and enhance drug stability. Additionally, the multifunctionality of nanomaterials allows for simultaneous imaging and therapy, facilitating early diagnosis and intervention. Key aspects covered include the interaction of nanomaterials with Aβ aggregates, the role of antioxidants in mitigating oxidative stress, and the potential of nanomedicine in alleviating neuroinflammation associated with AD. Furthermore, the safety, biocompatibility, and toxicity profiles of various nanomaterials are scrutinized to ensure their clinical applicability. In conclusion, this review underscores the pivotal role of nanomedicine and nanomaterials in revolutionizing AD treatment strategies. By specifically addressing BBB challenges, these innovative approaches offer new avenues for targeted drug delivery and improved therapeutic outcomes in the complex landscape of Alzheimer's disease.

A Compressive Review on Formulation and Evaluation of Herbal Niosomes containing Phaseolus vulgaris and zingiber officinale for the Treatment of Diabetes Mellitus

This study aimed to formulate and evaluate niosomes containing Phaseolus vulgaris (PV) and Zingiber officinale (ZO) for their antidiabetic activity. Niosomes, non-ionic surfactant vesicles, were prepared using PV and ZO extracts via the thin-film hydration method. The formulations were characterized for particle size, morphology, entrapment efficiency, and in vitro release profile. Antidiabetic activity was assessed through in vitro α-amylase inhibition assay and glucose uptake studies using differentiated 3T3-L1 adipocytes. The formulated niosomes exhibited a mean particle size within the nanometer range, indicating their suitability for drug delivery. Morphological examination revealed spherical vesicles with uniform size distribution. Entrapment efficiency of the bioactive constituents from PV and ZO extracts was found to be satisfactory. In vitro release studies demonstrated sustained release profiles over time, indicative of controlled drug delivery potential. Antidiabetic activity assessment revealed significant α-amylase inhibition by the niosomal formulations compared to free extracts. Furthermore, glucose uptake studies demonstrated enhanced glucose uptake by 3T3-L1 adipocytes treated with niosomes containing PV and ZO extracts compared to untreated cells.

Native and cationic cellulose nanofibril films enriched with avocado seed compounds as a green alternative for potential wound care applications

Cellulose nanofibrils (CNF) show great potential for skin wound care and healing due to their biocompatibility, non-cytotoxicity, and high swelling with good mechanical stability. In the presented study, for the first time native and cationized cellulose nanofibrils were used in combination with avocado seeds extracts obtained with different extraction methods (ASE), as an alternative to a well-known antibiotic, Clindamycin, to produce films with high and long-lasting antimicrobial efficacy. The swelling capacity of prepared films and extracts/antibiotic release kinetics were studied at different pH values to evaluate pH response behavior.All developed films exhibited high bacteriostatic and bactericidal activity against Gram-negative Escherichia coli and G-positive Staphylococcus aureus, resulting in up to 100 % bacterial reduction with the log reduction factor up to 5.64 or 6.50, at 14.2 mg of avocado seed extract or clindamycin integrated in the 1 cm2 of CNF film. The high swelling capacity (up to 65.67 %) and stability of avocado seed extracts-enriched CNF films provide a suitable moisture environment and a sustainable release (up to 40.98 % in 48 h) of bioactive compounds. The prepared antibacterial films' chemical and morphological characteristics and pH-responsive behavior proved the potential applications in the cosmetics, biomedicine, and pharmaceutical industry.

Toxicology study of a tissue anchoring paclitaxel prodrug

BackgroundLocal drug presentation made possible by drug-eluting depots provides benefits for a vast array of diseases, including cancer, microbial infection, and wound healing. Drug-eluting depots provide sustained drug release of therapeutics directly at disease sites with tunable kinetics, remove the need for drugs to access disease sites from circulation, and reduce the side effects associated with systemic therapy. Recently, we introduced an entirely novel approach to local drug presentation named Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs enables local drug presentation without any material carriers, capitalizing on innate tissue structures to anchor drugs at the site of administration.MethodsIn this report, we comprehensively evaluate the local and systemic toxicological profile of a paclitaxel version of TRAPs in mice by clinical observations, body weight monitoring, histopathological evaluations of injection sites and major organs, as well as blood and urine analyses.ResultsWe find that intradermal administration of TRAP-paclitaxel does not induce substantial toxic effects. Localized inflammatory responses were observed at the injection sites and secondary minimal, non-specific inflammation was observed in the liver. All other organs displayed unremarkable histological findings.ConclusionsThese findings support the potential of TRAP-paclitaxel as a promising candidate for localized cancer treatment, offering high-concentration drug delivery while mitigating scarring and adverse side effects.

Core-shell aerogel design for enhanced oral insulin delivery

Current protein-based therapies often rely on intravenous and subcutaneous injections leading to patient discomfort due to the need for frequent administration. Oral administration route presents a more patient-friendly alternative, but overcoming the challenge of low drug bioavailability remains paramount. This limitation is primarily attributed to protein degradation in the harsh gastric environment, enzymatic breakdown, and poor intestinal permeability. With their unique properties, such as high porosity and surface area, and easy scalability, aerogels offer a promising platform for oral delivery of therapeutic proteins. This study focused on the development and characterization of both conventional and core–shell aerogels derived from natural polysaccharides for the oral delivery of insulin, utilizing Humulin R® U-100 as the insulin source for the first time. Aerogels were produced via supercritical carbon dioxide (sc-CO2) drying of alginate gel beads. Scanning Electron Microscopy (SEM) images confirmed that the core–shell aerogels had higher uniformity in size and a more well-defined porous structure in comparison to conventional aerogels. Structural differences of two alginate sources were evaluated by Fourier Transform Infrared (FTIR) spectroscopy. A notable difference in encapsulation efficiencies was observed between conventional (12 %) and core–shell (53 %) aerogels, highlighting the superior carrier characteristics of the latter ones. In vitro insulin release profiles from the core–shell aerogels demonstrated their potential suitability for delivering regular/short-acting insulin therapeutics since only 30 % of insulin was released in Simulated Gastric Fluid (SGF) after 120 min, whereas 60 % of insulin was released in Simulated Intestinal Fluid (SIF) within the first hour followed by a sustained release stage.

Formulation and evaluation of Dapagliflozin -Loaded Ethosomes as Transdermal Drug Delivery Carriers: Statistical Design

Diabetes that includes risk factors for noncommunicable diseases like hypertension are only one example of the various situations in which chronic disease is connected with other conditions. Due to the challenges in overcoming the adverse effects of a complicated therapeutic treatment regimen, the treatments available for such chronic comorbid disorders are restricted and tough. The purpose of this research was to create and refine Dapagliflozin nano vesicular ethosomal gel for use in the treatment of patients with diabetes and cardiovascular disease. Different parameters, such as in-vitro skin permeation, skin irritation, in-vivo antidiabetic, and antihypertensive activities, were used to characterise the developed formulations. Dapagliflozin is a potent, oral, reversible, highly selective, and competitive inhibitor of human SGLT2 used to treat type 2 diabetes. The ethosomes that contain dapagliflozin are the focus of our current study. By incorporating this medication inside lipid nanocarriers, we were able to generate ethosomes, where the vesicular size and lipid used for formulation controlled the sustained release of medicines. The purpose of this study is to create Dapagliflozin-loaded ethosomes for the management of diabetes, and then to statistically optimise and characterise them. For ethosome improvement, we used a 33-level factorial design with three factors. The entrapment efficiency (Y1), vesicle size (Y2), zeta potential (Y3), and % CDR (Y4) were selected as the dependent variables, whereas phosphatidylcholine (X1), cholesterol (X2), and ethanol (X3) were selected as the independent factors. Following incorporation of the optimised ethosomes into Carbopol® 940 gel, their rheological behaviour, in-vitro release, and ex-vivo skin permeation studies were characterised. When compared to drug solutions, in vitro and ex vivo permeation studies yielded more positive results. All things considered, the ethosomal vesicles showed promise as a carrier, allowing for improved topical administration of Dapagliflozin. Keywords: Dapagliflozin, Diabetes, SGLT2, in-vitro release, and ex-vivo, phosphatidylcholine, topical administration, 33-level factorial design.

Enhanced Stability and Prolonged Insect-Repellent Action of Essential Oil-Loaded Nanostructured Lipid Carriers

Mosquito-borne diseases are a global health concern, necessitating effective and long-lasting insect repellents. This study investigated the physicochemical properties, stability, release kinetics, and efficacy of nanostructured lipid carriers (NLCs) and conventional emulsions (CEs) containing essential oils (NLC EOs) for insect-repellent applications. The droplet size of the CE was 18.46 ± 1.78 μm (Span 0.27 ± 0.06), while the NLC measured 136 ± 10.7 nm (PDI 0.26 ± 0.2) with a ζ-potential of –68 mV ± 2.2 mV (width 4.3 ± 0.1). EO incorporation did not significantly alter droplet size or ζ-potential. Gas chromatography–mass spectrometry confirmed an EO content of 8.57 ± 0.15 mg/mL in the CE EO and 7.75 ± 0.05 mg/mL in the NLC EO, with the NLC retaining a higher EO content over 90 days. Stability tests demonstrated consistent droplet sizes and ζ-potential for both formulations during storage. Release kinetics revealed diffusion-based release mechanisms, with the NLC providing a more sustained release than the CE. In a field test against mosquito species most frequently found in Greece, the NLC EO exhibited a significantly longer complete protection time (CPT) of 45 min, demonstrating more effective, long-lasting insect-repellent action. These findings revealed the NLC’s ability to retain volatile EO components efficiently, offering promising implications for long-lasting insect-repellent action.

Synthesis of a PVA-GO drug delivery system for sustained release of 4-methyl umbelliferon

Introduction 4-methyl umbelliferon (4MU) is a coumarin with anti-inflammatory, anti-thrombotic, enzyme-inhibiting, and antioxidant properties. Despite the benefits of the compound, it is eliminated very quickly from the blood circulation through the liver, kidney, and digestive system due to its hydrophobic properties. In this study we proposed to improve the durability of 4MU by binding of 4MU to poly vinyl alcohol (PVA) and graphene oxide (GO). Methods The PVA-4MU-GO complex was synthesized and characterized. Release of 4MU from the complex was investigated. H9C2 cells viability was investigated and the entry of complex to the cell was analyzed using flow cytometry. Result UV-Vis and FTIR studies confirmed the interaction of 4MU with PVA and GO. SEM measurement also revealed a particle size around 101 nm for PVA-4MU-GO complexes. The obtained results confirmed the assembly of PVA-4MU-GO. A continuous drug release for 8 d (160 h) was achieved. Cytotoxic studies on H9C2 cell showed that PVA-4MU-GO complex is dependent to the concentration of GO and also the relation of 4MU to GO. Sustained release and penetration of PVA-4MU-GO complex into the H9C2 cell were observed. Conclusion PVA-4MU-GO complex is recommended as an alternative for 4MU. Synthesis the complex of PVA-4MU-GO, verifying the correct binding, showing the in vitro release of the 4MU, as well as checking its toxicity and its gradual entry into the H9C2 cell, were performed in this study.

Injectable and Degradable Zwitterionic Cryogels as Cancer Vaccine Platforms to Prevent Cancer Recurrence after Surgery.

Cancer has become a highly prevalent disease and poses serious threats to human health. Conventional cancer treatments still face high risks of recurrence. Training the immune system to recognize and eliminate tumors via external stimulation, such as vaccines, emerges as a promising approach for cancer prevention and treatment. However, injectable vaccines may have limited immune activation, causing difficulties in maintaining long-term immune surveillance of tumorigenesis by tumor-specific cytotoxic T cells. Here, degradable zwitterionic cryogels were prepared using the cryogelation technique. The cryogenic preparation maintained the biological activities of tumor antigens and immune adjuvants loaded in the cryogels. The macroporous structure endowed the injectability of cryogels into the body via conventional syringes. In the presence of proteases, the cryogels degraded, allowing sustained release of antigens and adjuvants, ensuring continued dendritic cell (DC) recruitment and antigen presentation to maturing tumor-specific cytotoxic T cells. In vivo experiments demonstrated that the cryogel cancer vaccines elicited robust immune activation and effectively modulated tumor microenvironments. The combination with photothermal therapy significantly inhibited tumor growth, showing great potential for preventing postoperative recurrence. Additionally, the zwitterionic cryogels were biocompatible without obvious toxicities during degradation. The cryogels could serve as effective vaccine platforms to prevent cancer recurrence after surgery.

Bifunctional Oxaliplatin (IV) Prodrug Based pH-Sensitive PEGylated Liposomes for Synergistic Anticancer Action Against Triple Negative Breast cancer.

Triple negative breast cancer (TNBC) exhibits higher susceptibility towards oxaliplatin (OXA) due to a faulty DNA damage repair system. However, the unfavorable physicochemical properties and risk of toxicities limit the clinical utility of OXA. Therefore, to impart kinetic inertness, site-specific delivery, and multidrug action, an octahedral Pt(IV) prodrug was developed by using chlorambucil (CBL) as a choice of ligand. The combination of OXA and CBL exhibited synergistic anti-cancer action in TNBC cell lines. Further, to maximize tumor-specific delivery, intracellular accumulation, and in-vivo performance, the developed prodrug (OXA-CBL) was encapsulated in pH-sensitive PEGylated liposomes into (OXA-CBL/PEG-Liposomes). The fabricated liposomes had smaller particle size < 200nm and higher drug loading (~ 4.26 ± 0.18%). In-vitro release displayed pH-dependent sustained release for up to 48h. Cellular internalization revealed maximal uptake via clathrin-mediated endocytosis. The cytotoxicity assay showed reduced IC50 in the 4T1 (~ 1.559-fold) and MDA-MB-231 (~ 1.539-fold) cell lines than free OXA-CBL. In-vivo efficacy in 4T1-induced TNBC model revealed a marked increase in % tumor inhibition rate, while diminished % tumor burden in OXA-CBL/BSA-NPs treated animals. Toxicity assessment displayed no signs of systemic and hemolytic toxicity. Overall, delivery of Pt (IV) prodrug as a pH-sensitive PEGylated liposomes offers a safer and efficient system to manage TNBC.

Sustainable Immunomodulatory via Macrophage P2Y12 Inhibition Mediated Bioactive Patche for Peritendinous Antiadhesion.

Persistent anti-inflammatory responses are critical for the prevention of peritendinous adhesion. Although modified anti-adhesion barriers have been studied extensively, the immune response induced by the implants and the unclear mechanism limits their application. In this research, the advantage of the multi-functionalities of CA (caffeic acid) is taken to synthesize biodegradable poly (ester urethane) urea elastomers with ester- and carbamate-bonded CA (PEUU-CA). PEUU-CA is electrospun into bioactive patches that can uniquely present a sustained CA niche, referred to as BPSN. In the early stage of degradation, the breakage of the ester bond from BPSN is the dominant factor contributing to the early release of CA. In the later stage of BPSN degradation, the breakage of the ester and carbamate bonds contributes to the sustained release of CA. In vitro experiments showed that CA, when specifically bound to the P2Y12 receptor, down-regulated the expression and function of active P2Y12, effectively inhibiting the aberrant activation of macrophages and the secretion of inflammatory chemokines. BPSN addresses the foreign body reaction induced by macrophage-dominated biomaterial implantation and the issue of the short-term release of drugs at later stages of adhesion, providing a feasible strategy for the prevention and treatment of tissue adhesion, and more broadly, the well-known implant-derived inflammatory responses.