PMID- 37206216 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230522 IS - 2380-6761 (Print) IS - 2380-6761 (Electronic) IS - 2380-6761 (Linking) VI - 8 IP - 3 DP - 2023 May TI - Gellan gum spongy-like hydrogel-based dual antibiotic therapy for infected diabetic wounds. PG - e10504 LID - 10.1002/btm2.10504 [doi] LID - e10504 AB - Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)-based spongy-like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin-resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic-associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA-infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration. CI - (c) 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. FAU - Mendes, Ana Isabel AU - Mendes AI AUID- ORCID: 0000-0003-4724-0784 AD - Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho Braga Portugal. AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. FAU - Fraga, Alexandra Gabriel AU - Fraga AG AUID- ORCID: 0000-0003-2029-1629 AD - Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho Braga Portugal. AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. FAU - Peixoto, Maria Joao AU - Peixoto MJ AUID- ORCID: 0000-0002-4739-3409 AD - Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho Braga Portugal. AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. FAU - Aroso, Ivo AU - Aroso I AUID- ORCID: 0000-0002-0543-548X AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. AD - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine University of Minho Guimaraes Portugal. FAU - Longatto-Filho, Adhemar AU - Longatto-Filho A AUID- ORCID: 0000-0002-5779-9752 AD - Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho Braga Portugal. AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. AD - Molecular Oncology Research Center Barretos Cancer Hospital Barretos Sao Paulo Brazil. AD - Laboratory of Medical Investigation (LIM) 14 Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo Sao Paulo Brazil. FAU - Marques, Alexandra Pinto AU - Marques AP AUID- ORCID: 0000-0002-3222-0310 AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. AD - 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine University of Minho Guimaraes Portugal. FAU - Pedrosa, Jorge AU - Pedrosa J AUID- ORCID: 0000-0002-8204-4888 AD - Life and Health Sciences Research Institute (ICVS) School of Medicine University of Minho Braga Portugal. AD - ICVS/3B's-PT Government Associate Laboratory Braga/Guimaraes Portugal. LA - eng PT - Journal Article DEP - 20230321 PL - United States TA - Bioeng Transl Med JT - Bioengineering & translational medicine JID - 101689146 PMC - PMC10189450 OTO - NOTNLM OT - MRSA infection OT - antibiotics OT - diabetic ulcers OT - hydrogel OT - topical delivery COIS- The authors have no conflicts of interest to declare. EDAT- 2023/05/19 19:14 MHDA- 2023/05/19 19:15 PMCR- 2023/03/21 CRDT- 2023/05/19 15:38 PHST- 2022/11/14 00:00 [received] PHST- 2023/02/15 00:00 [revised] PHST- 2023/02/27 00:00 [accepted] PHST- 2023/05/19 19:15 [medline] PHST- 2023/05/19 19:14 [pubmed] PHST- 2023/05/19 15:38 [entrez] PHST- 2023/03/21 00:00 [pmc-release] AID - BTM210504 [pii] AID - 10.1002/btm2.10504 [doi] PST - epublish SO - Bioeng Transl Med. 2023 Mar 21;8(3):e10504. doi: 10.1002/btm2.10504. eCollection 2023 May.