The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of...The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds.In this work,a thermo-and pH-responsive hydrogel(P-CHP407)was prepared from an ad hoc synthesized amphiphilic poly(ether urethane)(CHP407)exposing a significant amount of-COOH groups(8.8±0.9 nmol/g_(polymer)).The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature(12.1◦C vs.14.6◦C,respectively)and gelation rate than CHP407 hydrogel,as rheologically assessed.Nanoscale hydrogel characterization by Low Field NMR(LF-NMR)spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels,as further proved by Dynamic Light Scattering analyses.In addition,P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer(pH 8)(e.g.,pH_(change_5min)=3.76 and 1.32,respectively).Moreover,LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing-COOH groups.Lastly,the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen:delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH,suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.展开更多
Chronic skin wounds affect more than 40 million patients globally and represent a severe growing burden for the healthcare systems,with annual costs expected to exceed$15 billions by 2022.To satisfy the huge demand fo...Chronic skin wounds affect more than 40 million patients globally and represent a severe growing burden for the healthcare systems,with annual costs expected to exceed$15 billions by 2022.To satisfy the huge demand for effective wound care products,different types of wound dressings have been introduced on the market dur-ing the last decades.Based on“the moist wound healing theory”postulated by Prof Winter in 1962,bandages were initially designed to recreate the optimal wound environment to favor the healing process.Then,thanks to the advancements achieved in biomaterial design and processing,biotechnology,imaging and electronic fields,great effort has been devoted to the development of formulations able to actively participate to tissue healing.Indeed,both the literature and the market report the design of medicated wound dressings,i.e.,wound care products releasing anti-microbial agents,anti-inflammatory drugs,or bioactive molecules.In this scenario,this review aims at critically describing the currently available wound care products,highlighting their proved effec-tiveness in wound management.Moreover,an overview of the main strategies exploited to design personalized wound dressings has been reported.Lastly,concerns on regulatory affairs and practical issues limiting the clinical translation of advanced research platforms have also been discussed.展开更多
Effective management of hard-to-close skin wounds is a challenging issue due to several co-morbidities in affected patients.Particularly,infections represent a major obstacle in wound healing.The design of efficient w...Effective management of hard-to-close skin wounds is a challenging issue due to several co-morbidities in affected patients.Particularly,infections represent a major obstacle in wound healing.The design of efficient wound treatments thus represents an urgent need.Injectable drug delivery hydrogels with intrinsic antimicrobial and antifungal properties were herein designed for perspective application in the mini-invasive treatment of hard-to-close wounds.First,an amphiphilic polyurethane was synthesized from Poloxamer■407 macrodiol and N-Boc diethanolamine chain extender(DHP407,M_(w)=33 kDa).Chain-extension reaction step was optimized to maximize the formation of-NH groups along the polymer chains(4.5×10^(20)±1.8×10^(19)-NH groups/g polymer),after Boc-caging group removal(D-DHP407).DHP407 and D-DHP407 water-based solutions were thermosensitive with slightly different Critical Micellar Concentration(17.5μg/mL vs.19.7μg/mL)and cluster hydrodynamic diameter(235.6±19.9 nm vs.260.1±20.5 nm),and similar Critical Micellar Temperature(22.5℃ vs.23.1℃).A polyurethane solution concentration(15%w/V)was selected by tube-inverting test and rheological analysis showing injectability,as evidenced by sol-to-gel transition at 27.7±0.6℃ for DHP407 and 29.7±0.6℃ for D-DHP407,within few minutes,at similar gelation kinetics.DHP407 and D-DHP407 hydrogels showed controlled release of Bovine Serum Albumin(BSA)model protein(1 mg/mL),with no burst phenomena.BSA released from DHP407 and D-DHP407 hydrogels at 24 h was 33.7±5.0% and 24.6±1.2%,respectively.D-DHP407 hydrogel was biocompatible and able to support NIH-3T3 cell proliferation.Furthermore,D-DHP407 hydrogel showed intrinsic antifungal and antibacterial activity against C.albicans and Gram-positive S.aureus and Gram-negative E.coli bacteria,injectability and capability to retain shape post-injection,making it promising for future use in the management of hard-to-close skin wounds.展开更多
基金This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No.685872-MOZART(www.mozartproject.eu).
文摘The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds.In this work,a thermo-and pH-responsive hydrogel(P-CHP407)was prepared from an ad hoc synthesized amphiphilic poly(ether urethane)(CHP407)exposing a significant amount of-COOH groups(8.8±0.9 nmol/g_(polymer)).The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature(12.1◦C vs.14.6◦C,respectively)and gelation rate than CHP407 hydrogel,as rheologically assessed.Nanoscale hydrogel characterization by Low Field NMR(LF-NMR)spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels,as further proved by Dynamic Light Scattering analyses.In addition,P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer(pH 8)(e.g.,pH_(change_5min)=3.76 and 1.32,respectively).Moreover,LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing-COOH groups.Lastly,the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen:delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH,suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.
文摘Chronic skin wounds affect more than 40 million patients globally and represent a severe growing burden for the healthcare systems,with annual costs expected to exceed$15 billions by 2022.To satisfy the huge demand for effective wound care products,different types of wound dressings have been introduced on the market dur-ing the last decades.Based on“the moist wound healing theory”postulated by Prof Winter in 1962,bandages were initially designed to recreate the optimal wound environment to favor the healing process.Then,thanks to the advancements achieved in biomaterial design and processing,biotechnology,imaging and electronic fields,great effort has been devoted to the development of formulations able to actively participate to tissue healing.Indeed,both the literature and the market report the design of medicated wound dressings,i.e.,wound care products releasing anti-microbial agents,anti-inflammatory drugs,or bioactive molecules.In this scenario,this review aims at critically describing the currently available wound care products,highlighting their proved effec-tiveness in wound management.Moreover,an overview of the main strategies exploited to design personalized wound dressings has been reported.Lastly,concerns on regulatory affairs and practical issues limiting the clinical translation of advanced research platforms have also been discussed.
文摘Effective management of hard-to-close skin wounds is a challenging issue due to several co-morbidities in affected patients.Particularly,infections represent a major obstacle in wound healing.The design of efficient wound treatments thus represents an urgent need.Injectable drug delivery hydrogels with intrinsic antimicrobial and antifungal properties were herein designed for perspective application in the mini-invasive treatment of hard-to-close wounds.First,an amphiphilic polyurethane was synthesized from Poloxamer■407 macrodiol and N-Boc diethanolamine chain extender(DHP407,M_(w)=33 kDa).Chain-extension reaction step was optimized to maximize the formation of-NH groups along the polymer chains(4.5×10^(20)±1.8×10^(19)-NH groups/g polymer),after Boc-caging group removal(D-DHP407).DHP407 and D-DHP407 water-based solutions were thermosensitive with slightly different Critical Micellar Concentration(17.5μg/mL vs.19.7μg/mL)and cluster hydrodynamic diameter(235.6±19.9 nm vs.260.1±20.5 nm),and similar Critical Micellar Temperature(22.5℃ vs.23.1℃).A polyurethane solution concentration(15%w/V)was selected by tube-inverting test and rheological analysis showing injectability,as evidenced by sol-to-gel transition at 27.7±0.6℃ for DHP407 and 29.7±0.6℃ for D-DHP407,within few minutes,at similar gelation kinetics.DHP407 and D-DHP407 hydrogels showed controlled release of Bovine Serum Albumin(BSA)model protein(1 mg/mL),with no burst phenomena.BSA released from DHP407 and D-DHP407 hydrogels at 24 h was 33.7±5.0% and 24.6±1.2%,respectively.D-DHP407 hydrogel was biocompatible and able to support NIH-3T3 cell proliferation.Furthermore,D-DHP407 hydrogel showed intrinsic antifungal and antibacterial activity against C.albicans and Gram-positive S.aureus and Gram-negative E.coli bacteria,injectability and capability to retain shape post-injection,making it promising for future use in the management of hard-to-close skin wounds.
