Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used gi...Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.展开更多
Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenar...Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse woundsituations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties andcapacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantagesin wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecularweighthyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging thatcould synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy inthree distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively,these findings underscore the potential of the sHA-CA patch as a promising candidate for the nextgenerationwound dressing.展开更多
Biomaterial-based drug delivery systems have been developed to expedite cartilage regeneration;however,challenges related to drug recovery,validation,and efficient drug delivery remain.For instance,compound K(CK)is a ...Biomaterial-based drug delivery systems have been developed to expedite cartilage regeneration;however,challenges related to drug recovery,validation,and efficient drug delivery remain.For instance,compound K(CK)is a major metabolite of ginsenosides that is known to protect against joint degeneration by inhibiting the production of inflammatory cytokines and the activation of immune cells.However,its effects on cartilage degradation and tissue regeneration remain unclear.Additionally,tissue-adhesive drug delivery depots that stably adhere to cartilage defects are required for CK delivery.In this study,CK-loaded adhesive patches were reported to seal cartilage defects and deliver CK to defect sites,preventing cartilage degradation and accelerating cartilage tissue regeneration.Adhesive patches are stable and suitable for application in surgical procedures under physiological conditions and show excellent adhesiveness to cartilage surfaces.In addition,there were no significant differences in the adhesive polymeric networks before and after CK loading.CK-loaded hydrocaffeic acid-conjugated chitosan patches significantly inhibited the stimulation of cartilage-degrading enzymes and apoptosis in osteoarthritic cartilage by releasing CK in cartilage defects.Additionally,the NFkB signaling pathway of released CK from the adhesive patches in the treatment of osteoarthritis is revealed.Thus,the CK-loaded adhesive patches are expected to significantly contribute to cartilage regeneration.展开更多
Periodontitis,a common chronic inflammatory disease caused by pathogenic bacteria,can be treated with diverse biomaterials by loading drugs,cytokines or proteins.However,these biomaterials often show unsatisfactory th...Periodontitis,a common chronic inflammatory disease caused by pathogenic bacteria,can be treated with diverse biomaterials by loading drugs,cytokines or proteins.However,these biomaterials often show unsatisfactory therapeutic efficiency due to their poor adhesion,short residence time in the wet and dynamic oral cavity and emerging drug resistance.Here we report a wet-responsive methacrylated gelatin(GelMA)-stabilized co-enzyme polymer poly(α-lipoic acid)(PolyLA)-based elastic patch with water-induced adhesion and softening features.In PolyLA-GelMA,the multiple covalent and hydrogen-bonding crosslinking between PolyLA and GelMA prevent PolyLA depolymerization and slow down the dissociation of PolyLA in water,allowing durable adhesion to oral periodontal tissue and continuous release of LA-based bioactive small molecule in periodontitis wound without resorting external drugs.Compared with the undifferentiated adhesion behavior of traditional adhesives,this wet-responsive patch demonstrates a favorable periodontal pocket insertion ability due to its non-adhesion and rigidity in dry environment.In vitro studies reveal that PolyLA-GelMA patch exhibits satisfactory wet tissue adhesion,antibacterial,blood compatibility and ROS scavenging abilities.In the model of rat periodontitis,the PolyLA-GelMA patch inhibits alveolar bone resorption and accelerates the periodontitis healing by regulating the inflammatory microenvironment.This biomacromolecule-stabilized coenzyme polymer patch provides a new option to promote periodontitis treatment.展开更多
Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines.However,many patients experience minimal benefits from certain medical treatments because of poor compliance,short retention t...Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines.However,many patients experience minimal benefits from certain medical treatments because of poor compliance,short retention times in the oral cavity,and inadequate drug efficacy.Herein,we present a novel hydrogel patch(SCE2)composed of a biopolymer matrix(featuring ultraviolet-triggered adhesion properties)loaded with cuttlefish ink nanoparticles(possessing pro-healing functions).Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light.SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species.These properties contribute to the elimination of bacteria and the management of the oxidation process,thus accelerating the healing phase’s progression from inflammation to proliferation.In studies involving diabetic rats with oral ulcers,the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area,facilitating rapid re-epithelialization,and fostering angiogenesis.In conclusion,this light-sensitive hydrogel patch offers a promising path to expedited wound healing,potentially transforming treatment strategies for clinical oral ulcers.展开更多
Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction(MI).However,the low retention of cells and drugs limits the...Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction(MI).However,the low retention of cells and drugs limits their therapeutic efficacies.Here,we propose a prefixed sponge carpet strategy,that is,aldehyde-dextran sponge(ODS)loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β-cyclodextrin@resveratrol(HP-β-CD@Res)is first bonded to the rat’s heart via capillary removal of interfacial water from the tissue surface,and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue.Then,an aqueous biocompatible hydrazided hyaluronic acid(HHA)solution encapsulating mesenchymal stem cells(MSCs)is impregnated into the anchored carpet to form HHA@ODS@HP-β-CD@Res hydrogel in situ via click reaction,thus prolonging the in vivo retention time of therapeutic drug and cells.Importantly,the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface,avoiding adhesion to other tissues.The embedded HP-β-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment,reduce cardiomyocyte apoptosis,and enhance the survival of transplanted MSCs,thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.展开更多
The purpose of this study was to investigate the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin. The...The purpose of this study was to investigate the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin. The patches were prepared with DURO-TAK (R) 87-2287 as a pressure-sensitive adhesive (PSA) containing 5% (w/w) of blonanserin and different concentrations of IPM. An in vitro release experiment was performed and the adhesive performance of the drug-in-adhesive patches with different concentrations of IPM was evaluated by a rolling ball tack test and a shear-adhesion test. The glass transition temperature (T-g) and rheological parameters of the drug-in-adhesive layers were determined to study the effect of IPM on the mechanical properties of the PSA. The results of the in vitro release experiment showed that the release rate of blonanserin increased with an increasing concentration of IPM. The rolling ball tack test and shear-adhesion test showed decreasing values with increasing IPM concentration. The results were interpreted on the basis of the IPM-induced plasticization of the PSA, as evidenced by a depression of the glass transition temperature and a decrease in the elastic modulus. In conclusion, IPM acted as a plasticizer on DURO-TAK (R) 87-2287, and it increased the release of blonanserin and affected the adhesive properties of the PSA. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND展开更多
Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combinat...Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination.To this end,we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer.The inner adhesive layer tightly and instantly adheres to the wound sites via-NHS chemistry;the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure;and the interlayer enhances the bulk resilience of the patch under excessive deformation.This complementary trilayer patch(TLP)possesses a unique combination of instant wet adhesion,high mechanical strength,and biological inertness.Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion.The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.展开更多
基金supported by the National Natural Scientific Foundation(82172186)Beijing Natural Scientific Foundation(L222126).
文摘Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.
基金support from the Ministry of Science and ICT of Korea(NRF-2021R1A2C2008821 and 2022H1D3A2A02093385)the Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korean government(21A0301L1-21)The Institute of Engineering Research at Seoul National University provided research facilities,and additional support came from the SNU Engineering-Medicine Collaboration grant.
文摘Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse woundsituations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties andcapacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantagesin wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecularweighthyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging thatcould synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy inthree distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively,these findings underscore the potential of the sHA-CA patch as a promising candidate for the nextgenerationwound dressing.
基金supported by a National Research Foundation of Korea(NRF)grant funded by the Korean Government(MSIT)(2022R1A4A1031259 and 2021R1I1A3041149)to E.-J.J.by a Korean Fund for Regenerative Medicine(KFRM)grant funded by the Korean Government(Ministry of Science and ICT,Ministry of Health&Welfare)(22A0103L1)to J.H.R.
文摘Biomaterial-based drug delivery systems have been developed to expedite cartilage regeneration;however,challenges related to drug recovery,validation,and efficient drug delivery remain.For instance,compound K(CK)is a major metabolite of ginsenosides that is known to protect against joint degeneration by inhibiting the production of inflammatory cytokines and the activation of immune cells.However,its effects on cartilage degradation and tissue regeneration remain unclear.Additionally,tissue-adhesive drug delivery depots that stably adhere to cartilage defects are required for CK delivery.In this study,CK-loaded adhesive patches were reported to seal cartilage defects and deliver CK to defect sites,preventing cartilage degradation and accelerating cartilage tissue regeneration.Adhesive patches are stable and suitable for application in surgical procedures under physiological conditions and show excellent adhesiveness to cartilage surfaces.In addition,there were no significant differences in the adhesive polymeric networks before and after CK loading.CK-loaded hydrocaffeic acid-conjugated chitosan patches significantly inhibited the stimulation of cartilage-degrading enzymes and apoptosis in osteoarthritic cartilage by releasing CK in cartilage defects.Additionally,the NFkB signaling pathway of released CK from the adhesive patches in the treatment of osteoarthritis is revealed.Thus,the CK-loaded adhesive patches are expected to significantly contribute to cartilage regeneration.
基金the support for this work from the National Natural Science Foundation of China(Grant No.52233008,52303201).
文摘Periodontitis,a common chronic inflammatory disease caused by pathogenic bacteria,can be treated with diverse biomaterials by loading drugs,cytokines or proteins.However,these biomaterials often show unsatisfactory therapeutic efficiency due to their poor adhesion,short residence time in the wet and dynamic oral cavity and emerging drug resistance.Here we report a wet-responsive methacrylated gelatin(GelMA)-stabilized co-enzyme polymer poly(α-lipoic acid)(PolyLA)-based elastic patch with water-induced adhesion and softening features.In PolyLA-GelMA,the multiple covalent and hydrogen-bonding crosslinking between PolyLA and GelMA prevent PolyLA depolymerization and slow down the dissociation of PolyLA in water,allowing durable adhesion to oral periodontal tissue and continuous release of LA-based bioactive small molecule in periodontitis wound without resorting external drugs.Compared with the undifferentiated adhesion behavior of traditional adhesives,this wet-responsive patch demonstrates a favorable periodontal pocket insertion ability due to its non-adhesion and rigidity in dry environment.In vitro studies reveal that PolyLA-GelMA patch exhibits satisfactory wet tissue adhesion,antibacterial,blood compatibility and ROS scavenging abilities.In the model of rat periodontitis,the PolyLA-GelMA patch inhibits alveolar bone resorption and accelerates the periodontitis healing by regulating the inflammatory microenvironment.This biomacromolecule-stabilized coenzyme polymer patch provides a new option to promote periodontitis treatment.
基金The financial backing for this research comes from the National Natural Science Foundation of China(82371016,21977081,82071170)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23C100001)+2 种基金the Zhejiang Provincial Science and Technology Project for Public Welfare(LGF21H140004)the Natural Science Foundation of Zhejiang Province(LQ22E030011)the Wenzhou Municipal Science and Technology Project(ZY2019009)。
文摘Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines.However,many patients experience minimal benefits from certain medical treatments because of poor compliance,short retention times in the oral cavity,and inadequate drug efficacy.Herein,we present a novel hydrogel patch(SCE2)composed of a biopolymer matrix(featuring ultraviolet-triggered adhesion properties)loaded with cuttlefish ink nanoparticles(possessing pro-healing functions).Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light.SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species.These properties contribute to the elimination of bacteria and the management of the oxidation process,thus accelerating the healing phase’s progression from inflammation to proliferation.In studies involving diabetic rats with oral ulcers,the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area,facilitating rapid re-epithelialization,and fostering angiogenesis.In conclusion,this light-sensitive hydrogel patch offers a promising path to expedited wound healing,potentially transforming treatment strategies for clinical oral ulcers.
基金National Natural Science Foundation of China(Grant No.52233008,51733006)National Key Research and Development Program(Grant No.2018YFA0703100).
文摘Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction(MI).However,the low retention of cells and drugs limits their therapeutic efficacies.Here,we propose a prefixed sponge carpet strategy,that is,aldehyde-dextran sponge(ODS)loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β-cyclodextrin@resveratrol(HP-β-CD@Res)is first bonded to the rat’s heart via capillary removal of interfacial water from the tissue surface,and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue.Then,an aqueous biocompatible hydrazided hyaluronic acid(HHA)solution encapsulating mesenchymal stem cells(MSCs)is impregnated into the anchored carpet to form HHA@ODS@HP-β-CD@Res hydrogel in situ via click reaction,thus prolonging the in vivo retention time of therapeutic drug and cells.Importantly,the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface,avoiding adhesion to other tissues.The embedded HP-β-CD@Res molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment,reduce cardiomyocyte apoptosis,and enhance the survival of transplanted MSCs,thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.
文摘The purpose of this study was to investigate the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin. The patches were prepared with DURO-TAK (R) 87-2287 as a pressure-sensitive adhesive (PSA) containing 5% (w/w) of blonanserin and different concentrations of IPM. An in vitro release experiment was performed and the adhesive performance of the drug-in-adhesive patches with different concentrations of IPM was evaluated by a rolling ball tack test and a shear-adhesion test. The glass transition temperature (T-g) and rheological parameters of the drug-in-adhesive layers were determined to study the effect of IPM on the mechanical properties of the PSA. The results of the in vitro release experiment showed that the release rate of blonanserin increased with an increasing concentration of IPM. The rolling ball tack test and shear-adhesion test showed decreasing values with increasing IPM concentration. The results were interpreted on the basis of the IPM-induced plasticization of the PSA, as evidenced by a depression of the glass transition temperature and a decrease in the elastic modulus. In conclusion, IPM acted as a plasticizer on DURO-TAK (R) 87-2287, and it increased the release of blonanserin and affected the adhesive properties of the PSA. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND
基金financially supported by the National Key Research and Development Program of China(2021YFB3800800,2018YFA0703000)the Science and Technology Program of Guangdong Province(2019B010941002)+3 种基金Science and Technology Program of Guangzhou(202206040001)the National Natural Science Foundation of China(32022041,U22A20157)the Key Research and Development Program of Guangzhou(20200702000,22020B1515120075)the Guangdong Basic and Applied Basic Research Foundation Outstanding Youth Project(2021B1515020064).
文摘Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination.To this end,we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer.The inner adhesive layer tightly and instantly adheres to the wound sites via-NHS chemistry;the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure;and the interlayer enhances the bulk resilience of the patch under excessive deformation.This complementary trilayer patch(TLP)possesses a unique combination of instant wet adhesion,high mechanical strength,and biological inertness.Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion.The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.
