Fabrication and Evaluation of Silk Sericin-Derived Hydrogel for the Release of the Model Drug Berberine.
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ABSTRACT:
SUBMITTER: Yan C
PROVIDER: S-EPMC8005982 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Microneedles are a relatively simple, minimally invasive and painless approach to deliver drugs across the skin. However, there remain limitations with this approach because of the materials most commonly utilized for such systems. Silk protein, with tunable and biocompatibility properties, is a useful biomaterial to overcome the current limitations with microneedles. Silk devices preserve drug activity, offer superior mechanical properties and biocompatibility, can be tuned for biodegradability, and can be processed under aqueous, benign conditions. In the present work, the fabrication of dense microneedle arrays from silk with different drug release kinetics is reported. The mechanical properties of the microneedle patches are tuned by post-fabrication treatments or by loading the needles with silk microparticles, to increase capacity and mechanical strength. Drug release is further enhanced by the encapsulation of the drugs in the silk matrix and coating with a thin dissolvable drug layer. The microneedles are used on human cadaver skin and drugs are delivered successfully. The various attributes demonstrated suggest that silk-based microneedle devices can provide significant benefit as a platform material for transdermal drug delivery.
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Project description:To fabricate environmentally sensitive hydrogels with better biocompatibility, natural materials such as protein and polysaccharide have been widely used. Environmentally sensitive hydrogels can be used as a drug carrier for sustained drug release due to its stimulus responsive performance. The relationship between the internal structure of hydrogels and their drug delivery behaviors remains indeterminate. In this study, environmentally sensitive hydrogels fabricated by blending silk fibroin/chitosan with different mass ratios were successfully prepared using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (EDC)/N-Hydroxysuccinimide (NHS) cross-linking agent. Scanning-electron microscopy (SEM) images showed the microcosmic surface of the gel had a 3-D network-like and interconnected pore structure. The N2 adsorption-desorption method disclosed the existence of macroporous and mesoporous structures in the internal structure of hydrogels. Data of compression tests showed its good mechanical performance. The swelling performance of hydrogels exhibited stimuli responsiveness at different pH and ion concentration. With the increase of pH and ion concentration, the swelling ratios of hydrogels (silk fibroin (SF)/ chitosan (CS) = 8/2 and 7/3) decreased. Methylene blue (MB) was loaded into the hydrogels to confirm the potential of sustained drug release and pH-responsive behavior. Therefore, due to the porous structure, stable mechanical strength, stimuli responsive swelling performance, and drug release behaviors, the SF/CS composite hydrogels have potential applications in controlled drug release.
| S-EPMC6960489 | biostudies-literature
Project description:Sericin, a major component of silk, has a long history of being discarded as a waste during silk processing. The value of sericin for tissue engineering is underestimated and its potential application in regenerative medicine has just begun to be explored. Here we report the successful fabrication and characterization of a covalently-crosslinked 3D pure sericin hydrogel for delivery of cells and drugs. This hydrogel is injectable, permitting its implantation through minimally invasive approaches. Notably, this hydrogel is found to exhibit photoluminescence, enabling bioimaging and in vivo tracking. Moreover, this hydrogel system possesses excellent cell-adhesive capability, effectively promoting cell attachment, proliferation and long-term survival of various types of cells. Further, the sericin hydrogel releases bioactive reagents in a sustained manner. Additionally, this hydrogel demonstrates good elasticity, high porosity, and pH-dependent degradation dynamics, which are advantageous for this sericin hydrogel to serve as a delivery vehicle for cells and therapeutic drugs. With all these unique features, it is expected that this sericin hydrogel will have wide utility in the areas of tissue engineering and regenerative medicine.
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Project description:BackgroundBerberine (BBR) broadly found in medicinal plants has a major application in pharmacological therapy as an anticancer drug. Clinical applications of this promising natural drug are limited due to its poor water solubility and low bioavailability.ObjectiveIn this study, for the first time, we synthesized core-shell BBR-loaded PLA nanoparticles (NPBs) by using coaxial electrospray (CES) to solve the poor bioavailability of BBR.MethodsThree-factor (feeding rate, polymeric solution concentration and applied voltage), three-level, Box-Behnken design was used for optimization of the size and particle size distribution of the prepared NPBs.ResultsBased on the results of response surface methodology, the NPBs with the mean size of 265 nm and particle size distribution of 43 nm were synthesized. A TEM image was used to well illustrate the core-shell structure of the NPBs. Encapsulation efficiency and BBR loading capacity for the optimized NPBs were determined at about 81% and 7.5%, respectively. Release of NPBs was examined at pH 7.4 and 5.8. NPBs had a slower release profile than free BBR in both pH values, and the rate of BBR release was more and faster in acidic pH than in physiological one. Effects of the NPBs on the drug release were confirmed by data fitting with six kinetic models. NPBs showed an increased cytotoxic efficacy against HCT116 cells (IC50 = 56 μM), while NIH3T3 cells, non-neoplastic fibroblast cells, (IC50 > 150 μM) were less affected by NPBs. Flow cytometry demonstrated that the cellular uptake of NPBs were higher than BBR at different concentrations.ConclusionsA new approach was developed in this study to prepare NPBs using the CES process for improving the efficiency and controlled BBR release. It is concluded that nano-scaled NPBs prepared by CES can improve toxicity and chemotherapeutic properties of BBR against cancerous cells. We believe that these NPBs can exhibit further potential in cancer drug delivery systems. Graphical abstract.
| S-EPMC7214554 | biostudies-literature
Project description:Objective: To fabricate and investigate the properties of fibroin and polyvinyl alcohol (PVA) hydrogels containing sericin prepared using high-pressure carbon dioxide (CO2). Approach: In this study, fibroin/PVA hydrogels with and without sericin were prepared using the high-pressure CO2 method. The physical and mechanical properties of the hydrogels were investigated using field-emission scanning electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry, and the swelling, water retention, and compressive properties were assessed. Results: The hydrogels obtained from the combination of fibroin and PVA presented a compositional gradient along the hydrogel thickness and structure. The upper layer of the hydrogel consisted of a fibroin-based hydrogel blended with PVA, whereas the lower layer contained only fibroin. The mechanical properties regarding compression of the fibroin/PVA hydrogel were significantly better than those of the pure fibroin hydrogel, for hydrogels with and without sericin. Moreover, the mechanical properties of the hydrogels with sericin were significantly better than those without sericin. The water contents of all samples were >90%. Innovation: This study assessed a new combination of a wound healing agent and a biomaterial dressing. Moreover, this hydrogel production technique used a clean method without the need for a chemical crosslinking agent. Conclusion: The combination of the fibroin and PVA hydrogel and sericin prepared using the high-pressure CO2 method led to good physical properties. This material may be a candidate for medical applications.
| S-EPMC6855286 | biostudies-literature
Project description:In the present work, a sustained-release film composed of silk fibroin (SF), curcumin (Cur), glutaraldehyde (GA), and glycerol (Gly) was prepared successfully for wound dressings. Features relevant to wound dressings of SF/Gly/GA/Cur film were assessed. Physical and chemical properties of the fabricated materials were also characterized. The results showed that the prepared SF/Gly/GA/Cur film demonstrated a good sustained-release performance, flexibility, and gas permeability. In addition, it was found that the prepared SF/Gly/GA/Cur film possessed the capability to effectively inhibit the growth of bacteria and prevent bacterial penetration with a suitable water vapor transmission rate. Furthermore, the prepared composite film was non-cytotoxic, which makes it an ideal material for wound dressings.
| S-EPMC6829413 | biostudies-literature
Project description:The application of sericin hydrogels is limited mainly due to their poor mechanical strength, tendency to be brittle and inconvenient sterilization. To address these challenges, a sericin hydrogel exhibiting outstanding physical and chemical properties along with cytocompatibility was prepared through crosslinking genipin with degraded sericin extracted from fibroin deficient silkworm cocoons by the high temperature and pressure method. Our reported sericin hydrogels possess good elasticity, injectability, and robust behaviors. The 8% sericin hydrogel can smoothly pass through a 16 G needle. While the 12% sericin hydrogel remains intact until its compression ratio reaches 70%, accompanied by a compression strength of 674 kPa. 12% sericin hydrogel produce a maximum stretch of 740%, with breaking strength and tensile modulus of 375 kPa and 477 kPa respectively. Besides that, the hydrogel system demonstrated remarkable cell-adhesive capabilities, effectively promoting cell attachment and, proliferation. Moreover, the swelling and degradation behaviors of the hydrogels are pH responsiveness. Sericin hydrogel releases drugs in a sustained manner. Furthermore, this study addresses the challenge of sterilizing sericin hydrogels (sterilization will inevitably lead to the destruction of their structures). In addition, it challenges the prior notion that sericin extracted under high temperature and pressure is difficult to directly cross-linked into a stable hydrogel. This developed hydrogel system in this study holds promise to be a new multifunctional platform expanding the application area scope of sericin.
| S-EPMC10742692 | biostudies-literature
Project description:The effectiveness of cell culture and tissue regeneration largely depends on the structural and physiochemical characteristics of tissue-engineering scaffolds. Hydrogels are frequently employed in tissue engineering because of their high-water content and strong biocompatibility, making them the ideal scaffold materials for simulating tissue structures and properties. However, hydrogels created using traditional methods have low mechanical strength and a non-porous structure, which severely restrict their application. Herein, we successfully developed silk fibroin glycidyl methacrylate (SF-GMA) hydrogels with oriented porous structures and substantial toughness through directional freezing (DF) and in situ photo-crosslinking (DF-SF-GMA). The oriented porous structures in the DF-SF-GMA hydrogels were induced by directional ice templates and maintained after photo-crosslinking. The mechanical properties, particularly the toughness, of these scaffolds were enhanced compared to the traditional bulk hydrogels. Interestingly, the DF-SF-GMA hydrogels exhibit fast stress relaxation and variable viscoelasticity. The remarkable biocompatibility of the DF-SF-GMA hydrogels was further demonstrated in cell culture. Accordingly, this work reports a method to prepare tough SF hydrogels with aligned porous structures, which can be extensively applied to cell culture and tissue engineering.
| S-EPMC10048404 | biostudies-literature
Project description:Although alginate hydrogels have been extensively studied for tissue engineering applications, their utilization is limited by poor mechanical strength, rapid drug release, and a lack of cell adhesive ability. Aiming to improve these properties, we employ the interpenetrating hydrogel design rationale. Using alginate and sericin (a natural protein with many unique properties and a major component of silkworm silk), we develop an interpenetrating polymer network (IPN) hydrogel comprising interwoven sericin and alginate double networks. By adjusting the sericin-to-alginate ratios, IPNs' mechanical strength can be adjusted to meet stiffness requirements for various tissue repairs. The IPNs with high sericin content show increased stability during degradation, avoiding pure alginate's early collapse. These IPNs have high swelling ratios, benefiting various applications such as drug delivery. The IPNs sustain controlled drug release with the adjustable rates. Furthermore, these IPNs are adhesive to cells, supporting cell proliferation, long-term survival and migration. Notably, the IPNs inherit sericin's photoluminescent property, enabling bioimaging in vivo. Together, our study indicates that the sericin-alginate IPN hydrogels may serve as a versatile platform for delivering cells and drugs, and suggests that sericin may be a building block broadly applicable for generating IPN networks with other biomaterials for diverse tissue engineering applications.
| S-EPMC4513302 | biostudies-other
Project description:Silk has traditionally been used as a suture material because of its excellent mechanical properties and biocompatibility. These properties have led to the development of different silk-based material formats for tissue engineering and regenerative medicine. Although there have been a small number of studies about the use of silk particles for drug delivery, none of these studies have assessed the potential of silk to act as a stimulus-responsive anticancer nanomedicine. This report demonstrates that an acetone precipitation of silk allows the formation of uniform silk nanoparticles (98 nm diameter, polydispersity index 0.109), with an overall negative surface charge (-33.6 ± 5.8 mV), in a single step. Silk nanoparticles are readily loaded with doxorubicin (40 ng doxorubicin/?g silk) and show pH-dependent release (pH 4.5? 6.0 > 7.4). In vitro studies with human breast cancer cell lines demonstrates that the silk nanoparticles are not cytotoxic (IC50 > 120 ?g mL(-1) ) and that doxorubicin-loaded silk nanoparticles are able to overcome drug resistance mechanisms. Live cell fluorescence microscopy studies show endocytic uptake and lysosomal accumulation of silk nanoparticles. In summary, the pH-dependent drug release and lysosomal accumulation of silk nanoparticles demonstrate the ability of drug-loaded silk nanoparticles to serve as a lysosomotropic anticancer nanomedicine.
| S-EPMC3808531 | biostudies-literature