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Custom-design of intrinsically antimicrobial polyurethane hydrogels as multifunctional injectable delivery systems for mini-invasive wound treatment

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Engineered Regeneration 2021年第1期2卷 263-278页

作者： Rossella Laurano Valeria Chiono Chiara Ceresa letizia fracchia Alice Zoso Gianluca Ciardelli Monica Boffito Mechanical and Aerospace Engineering Department Politecnico di TorinoCorso Duca degli Abruzzi 24Torino 10129Italy Department of Pharmaceutical Sciences Universitadel Piemonte Orientale A.AvogadroLargo Guido Donegani 2Novara 28100Italy

Effective management of hard-to-close skin wounds is a challenging issue due to several co-morbidities in affected ***,infections represent a major obstacle in wound *** design of efficient wound treatments thus represents an urgent *** drug delivery hydrogels with intrinsic antimicrobial and antifungal properties were herein designed for perspective application in the mini-invasive treatment of hard-to-close ***,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 ***407 and D-DHP407 hydrogels showed controlled release of Bovine Serum Albumin(BSA)model protein(1 mg/mL),with no burst *** 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 ***,D-DHP407 hydrogel showed intrinsic antifungal and antibacterial activity against *** and Gram-positive *** and Gram-negative *** bacteria,injectability and capability to retain shape post-injection,making it promising for future use in the management of hard-to-close skin wounds.

关键词： Antimicrobial poly(ether urethane)s Drug delivery systems Injectable formulations Antibiotic-free treatments Wound healing Thermosensitive hydrogels

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