The use of conductive materials to promote the activity of electrically responsive cells is an effective means of accelerating wound healing. This article focuses on recent advancements in conductive ...materials, with emphasis on overviewing their incorporation with non‐conducting polymers to fabricate electroactive wound dressings. The characteristics of these electroactive dressings are deliberated, and the mechanisms on how they accelerate the wound healing process are discussed. Potential directions for the future development of electroactive wound dressings and their potential in monitoring the course of wound healing in vivo concomitantly are also proposed.
In a skin wound that disrupts the epithelial barrier, the trans‐epithelial potential falls, establishing an endogenous electric current from the unwounded epidermis to the wound. The application of an electroactive wound dressing on top of the wound enables conduction and more effective distribution of the endogenous electric current, stimulating the migration of host cells, ultimately accelerating healing of the wound.
Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood–brain barrier (BBB), which are located between the gut and the ...brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on β‐glucans using a disulfide‐containing linker. Following oral administration in glioma‐bearing mice, the as‐prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/hitchhiked by local macrophages (Mϕ). The Mϕ‐hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor‐overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut‐to‐brain oral drug delivery platform for the well‐targeted treatment of gliomas.
Following oral administration, a prodrug transpasses the intestinal epithelial barrier via M cells, and then undergoes endocytosis by resident macrophages. The macrophage‐hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the blood–brain barrier, ultimately penetrating a brain tumor. The tumor‐overexpressed glutathione cleaves the disulfide bond within the prodrug, releasing the active drug, facilitating antitumor efficacy.
Vaccination via the oral administration of an antigen faces many challenges, including gastrointestinal (GI) proteolysis and mucosal barriers. To limit GI proteolysis, a biomimetically mineralized ...aluminum‐based metal–organic framework (Al‐MOF) system that is resistant to ambient temperature and pH and can act synergistically as a delivery vehicle and an adjuvant is synthesized over a model antigen ovalbumin (OVA) to act as armor. To overcome mucosal barriers, a yeast‐derived capsule is used to carry the Al‐MOF‐armored OVA as a “Trojan Horse”‐like transport platform. In vitro experiments reveal that the mineralization of Al‐MOFs forms an armor on OVA that protects against highly acidic and degradative GI conditions. However, the mineralized Al‐MOFs can gradually disintegrate in a phosphate ion‐containing simulated intracellular fluid, slowly releasing their encapsulated OVA. In vivo studies reveal that the “Trojan Horse”‐like transport platform specifically targets intestinal M cells, favoring the transepithelial transport of the Al‐MOF‐armored OVA, followed by subsequent endocytosis in local macrophages, ultimately accumulating in mesenteric lymph nodes, yielding long‐lasting, high‐levels of mucosal S‐IgA and serum IgG antibodies. Such an engineered delivery platform may represent a promising strategy for the oral administration of prophylactic or therapeutic antigens for vaccination.
A yeast‐derived capsule functions as a “Trojan Horse”‐like transport platform to carry the immune‐activating aluminum metal–organic framework (Al‐MOF)‐armored ovalbumin (OVA). Following oral administration, the delivery platform protects the armored OVA during gastrointestinal transport and specifically targets M cells, increasing its transepithelial absorption, followed by subsequent endocytosis in local macrophages. The Al‐MOF‐armored OVA ultimately accumulates in mesenteric lymph nodes, generating potent and long‐lasting immune responses.
•Active and intelligent films prepared from gellan gum and Clitoria ternatea extract.•Antioxidant, antimicrobial and colorimetric pH indicator properties of the films.•Gellan gum enhancs the ...stability and controls the release of CT anthocyanins.•Soy protein affects physical and mechanical properties and anthocyanins release rates.•The pH indicator films change their colors in response to seafood spoilage.
Active and intelligent packaging films with multiple functions including antioxidant, antibacterial and colorimetric pH indicator properties were developed by incorporating Clitoria ternatea (CT) extract into gellan gum (G) film. G enhanced the stability of CT anthocyanins and allowed the anthocyanins to release from G film in a pH-responsive behavior. Heat-treated soy protein isolate (HSPI) was able to interact with G and CT anthocyanins through the formation of electrostatic forces and covalent bonds. G film blended with HSPI greatly reduced the swelling capacity of G/HSPI composite film and controlled the anthocyanins release at pH greater than 6.0. The physical and mechanical properties of G films such as hydrophobicity, water vapor permeability, swelling capacity and tensile strength were also significantly modified by addition of HSPI to G films. The smart films changed their color with the increase of total volatile basic nitrogen (TVBN) values during progressive spoilage of shrimp, revealing their potential application for monitoring seafood freshness.
•Development of a novel mutli-stimuli-responsive fucoidan/protamine nanoparticle.•P-selectin targeting, charge conversion, and stimuli-responsive properties.•Drug release was triggred by enzymatic ...digestion and acidic intracellular pH.•DOX-loaded nanoparticles improved inhibitory effect against MDA-MB-468 cancer cells.
Fucoidan, a sulfated marine polysaccharide, has many potential biological functions, including anticancer activity. Recently, fucoidan has been reported to target P-selectin expressed on metastatic cancer cells. Increasing research attention has been devoted to the developments of fucoidan-based nanomedicine. However, the application of traditional chitosan/fucoidan nanoparticles in anticancer drug delivery may be limited due to the deprotonation of chitosan at a pH greater than 6.5. In this study, a mutli-stimuli-responsive nanoparticle self-assembled by fucoidan and a cationic polypeptide (protamine) was developed, and their pH-/enzyme-responsive properties were characterized by circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and zeta potential analysis. Enzymatic digestion and acidic intracellular microenvironment (pH 4.5–5.5) in cancer cells triggered the release of an anticancer drug (doxorubicin) from the nanoparticles. The protamine/fucoidan complex nanoparticles with P-selectin mediated endocytosis, charge conversion and stimuli-tunable release properties showed an improved inhibitory effect against a metastatic breast cancer cell line (MDA-MB-231).
•Porous magnetic chitosan-citrate gel beads (CCGB) were prepared for Cu(II) removal.•Chitosan was cross-linked with citric acid to improve its adsorption capacity.•Adsorption isotherms and kinetics ...fit the Freundlich and pseudo-second-order models.•Thermodynamic parameters indicate a spontaneous and exothermic adsorption process.
Magnetic chitosan beads were synthesized by incorporating N,O-carboxymethyl chitosan-coated magnetic nanoparticles (NOCC-MNPs) into chitosan-citrate gel beads (CCGBs) for adsorbing Cu(II) ions. An increase of Cu(II) adsorption capacity was due to the combined chelation effects from the electron-donating functional groups in the CCGBs and NOCC-MNPs. Moreover, the paramagnetic susceptibility of Cu(II) citrate chelates could further improve the Cu(II) adsorption efficiency through the force of magnetic attraction. The adsorption data of the magnetic CCGBs fitted well with the Freundlich model, whereas the adsorption kinetics followed the pseudo-second-order kinetic model. The maximal adsorption capacity as estimated by the Langmuir model was 294.11mg/g. The adsorption thermodynamic parameters indicated that the involved process should be spontaneous and exothermic.
Display omitted
•Self-assembled nanoparticles from arginine-modified chitosan and thiolated fucoidan.•Exhibiting pH-sensitive assembly-disassembly and drug release properties.•Regulating the opening ...of tight junction and inhibiting P-glycoprotein (P-gp).•Increasing the permeability of hydrophilic macromolecules and hydrophobic compounds.
Self-assembled nanoparticles (NPs) from arginine-modified chitosan (CS-N-Arg) and thiolated fucoidan (THL-fucoidan) were synthesized to enhance the transport of dextran and curcumin across intestinal epithelial cell layer. CS-N-Arg/THL-fucoidan NPs exhibited a pH-sensitive assembly-disassembly and drug release property. Evaluations of the NPs in enhancing the transport of a hydrophilic macromolecule (FITC-dextran) and a hydrophobic drug (curcumin) were investigated in Caco-2 cell monolayers. The cationic CS-N-Arg in the NPs induced disruption of intestinal epithelial tight junctions as indicated by the decrease of transepithelial electrical resistance (TEER). Permeation studies revealed that the NPs enhanced the paracellular permeation of macromolecular dextran through the monolayer barrier. In addition, the multifunctional NPs increased the permeability of rhodamine 123 because the thiomer THL-fucoidan in the NPs inhibited P-glycoprotein. Cellular uptake and permeability of curcumin encapsulated in the NPs were improved due to increasing their water solubility and stability.
Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer ...(TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.
•Fucoidan from Laminaria japonica exerts antitumor effects.•Fucoidan suppresses proangiogenesis and micrometastasis in TNBC.•Fucoidan blocks MAPK and PI3K signaling in TNBC.
Hydroxypropyl chitosan (HPCS) has recently attracted increasing attention in biomedical applications because it has enhanced water solubility, excellent biocompatibility, and better antioxidant and ...antibacterial activities compared with chitosan. However, HPCS doesn't meet the mechanical strength requirement in bone tissue engineering and is not suitable for cell adhesion and growth because of its hydrophilic nature and low crystallinity. In this study, nano-scaled hydroxyapatite (n-HA) and HPCS were synthesized, respectively, and then n-HA/HPCS nanocomposite scaffolds were developed by incorporating n-HA into HPCS matrix accompanied with crosslinking of HPCS by a naturally occurring compound, genipin (GP), which in turn greatly altered the hydrophilicity and mechanical properties. The nanocomposite scaffolds showed an open structure with interconnected pores and a rough morphology with n-HA inserted in the GP-crosslinked HPCS matrix. The porosity, swelling capacity, compressive strength, fluorescence emission and degradation rate can be regulated by varying GP concentrations and n-HA contents. An osteoconductive and osteogenic marine algae polysaccharide, fucoidan, was further adsorbed to the composite scaffolds via electrostatic interactions. Incorporation of n-HA and adsorption of FD into the composite scaffolds increased ALP activity in 7F2 osteoblast cells and promoted their mineralization. The FD-adsorbed n-HA/HPCS composite scaffolds can be a potential biomaterial for BTE applications.
Display omitted
•Genipin-crosslinked nanohydroxyapatite/hydroxypropyl chitosan composite scaffolds were developed.•Genipin and nanohydroxyapatite greatly reduce the hydrophicity and improve the mechanical property.•The scaffolds possessed interconnected porous structures, good compressive strength and biodegradability.•An osteoconductive and osteogenic fucoidan can be further adsorbed to the scaffolds.•Nanohydroxyapatite and fucoidan combined in the scaffolds increased ALP activity and mineralization in osteoblast cells.
Oral administration is a highly attractive approach for the delivery of protein drugs. However, oral protein therapeutics typically exhibit extremely poor bioavailability due to the harsh ...gastrointestinal (GI) environments and low permeability of protein across the intestinal barrier. Trimethyl chitosan (TMC) shows excellent mucoadhesive and absorption-enhancing properties while fucoidan (FD) has hypoglycemic effects and can prevent diabetes-related complications. Here we report, for the first time, that TMC combined with FD can be developed to a mutlifunctional nanoplatform for enhancing the transepithelial permeation of insulin through the intestinal epithelial cell barrier and inhibiting the α-glucosidase activity. TMC and FD self-assembled into spherical nanoparticles (NPs) for insulin encapsulation. TMC/FD NPs protected insulin against degradation by releasing insulin in a pH-dependent manner in the gastrointestinal tract fluids. The NPs were able to modulate the barrier function of the Caco-2 intestinal epithelial cell monolayer, and enhance paracellular transport of insulin across the intestinal barrier. TMC/FD NPs also showed α-glucosidase inhibitory activity, with an inhibition ratio of 33.2% at 2 mg/mL. The superior transepithelial absorption enhancing property of the TMC/FD NPs is expected to combine in the future with the functions of fucoidan against diabetes-related complications for development of advanced mutlifunctional therapeutic platforms for diabetes.
