Valappil, Sabeel P.Abou Neel, Ensanya A.Zakir Hossain, Kazi M.Paul, WilliCherukaraveedu, DurgadasWade, BenjaminAnsari, Tahera IHope, Christopher K.Higham, Susan M.Sharma, Chandra P.2024-01-022024-01-022023-12-19Valappil, S. P., Abou Neel, E. A., Hossain, K. M. Z., Paul, W., Cherukaraveedu, D., Wade, B., Ansari, T. I., Hope, C. K., Higham, S. M., & Sharma, C. P. (2024). Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection. International Journal of Biological Macromolecules, 258(1), article-number 128838. https://doi.org/10.1016/j.ijbiomac.2023.1288380141-813010.1016/j.ijbiomac.2023.128838http://hdl.handle.net/10034/628400Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections.https://creativecommons.org/licenses/by-nc-nd/4.0/AntibacterialGalliumIn vivo wound healingLactoferrinPseudomonas aeruginosaArticleInternational Journal of Biological Macromolecules