Generic placeholder image

Current Drug Delivery


ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Roxithromycin and rhEGF Co-loaded Reactive Oxygen Species Responsive Nanoparticles for Accelerating Wound Healing

Author(s): Jun Ding, Dan Chen, Jun Hu, Dinglin Zhang, Yajun Gou* and Yaguang Wu*

Volume 21, Issue 5, 2024

Published on: 15 June, 2023

Page: [753 - 762] Pages: 10

DOI: 10.2174/1567201820666230512103750

Price: $65


Background: Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation.

Objective: Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat Staphylococcus aureus-infected wounds.

Methods: By using our previously prepared reactive oxygen species-responsive material (Oxi-αCD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-αCD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-αCD NPs) were successfully fabricated. The in vivo efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds.

Results: ROX/Oxi-αCD NPs and rhEGF/ROX/Oxi-αCD NPs had a spherical structure and their particle sizes were 164 ± 5 nm and 190 ± 8 nm, respectively. The in vitro antibacterial experiments showed that ROX/Oxi-αCD NPs had a lower minimum inhibitory concentration than ROX. The in vivo animal experiments demonstrated that rhEGF/ROX/Oxi-αCD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-αCD NPs (P < 0.05).

Conclusion: ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.

Keywords: Bacteria-infected wounds, roxithromycin, recombinant human epidermal growth factor, nanomedicine, reactive oxygen species, Staphylococcus aureus.

Graphical Abstract
He, J.; Qiao, Y.; Zhang, H.; Zhao, J.; Li, W.; Xie, T.; Zhong, D.; Wei, Q.; Hua, S.; Yu, Y.; Yao, K.; Santos, H.A.; Zhou, M. Gold–silver nanoshells promote wound healing from drug-resistant bacteria infection and enable monitoring via surface-enhanced Raman scattering imaging. Biomaterials, 2020, 234, 119763.
[] [PMID: 31978871]
Luo, Z.; Liu, J.; Lin, H.; Ren, X.; Tian, H.; Liang, Y.; Wang, W.; Wang, Y.; Yin, M.; Huang, Y.; Zhang, J. In situ fabrication of nano ZnO/BCM Biocomposite based on MA modified bacterial cellulose membrane for antibacterial and wound healing. Int. J. Nanomedicine, 2020, 15, 1-15.
[] [PMID: 32021161]
Tang, S.; Zheng, J. Antibacterial activity of silver nanoparticles: Structural effects. Adv. Healthc. Mater., 2018, 7(13), 1701503.
[] [PMID: 29808627]
Burdușel, A.C.; Gherasim, O.; Grumezescu, A.M.; Mogoantă L.; Ficai, A.; Andronescu, E. Biomedical applications of silver nanoparticles: An Up-to-Date overview. Nanomaterials, 2018, 8(9), 681.
[] [PMID: 30200373]
Kumar, S.S.D.; Rajendran, N.K.; Houreld, N.N.; Abrahamse, H. Recent advances on silver nanoparticle and biopolymer-based biomaterials for wound healing applications. Int. J. Biol. Macromol., 2018, 115, 165-175.
[] [PMID: 29627463]
Lin, Z.; Wu, T.; Wang, W.; Li, B.; Wang, M.; Chen, L.; Xia, H.; Zhang, T. Biofunctions of antimicrobial peptide-conjugated alginate/hyaluronic acid/collagen wound dressings promote wound healing of a mixed-bacteria-infected wound. Int. J. Biol. Macromol., 2019, 140, 330-342.
[] [PMID: 31421174]
Zhang, C.; Yang, M. Antimicrobial peptides: From design to clinical application. Antibiotics, 2022, 11(3), 349.
[] [PMID: 35326812]
Barreto-Santamaría, A.; Arévalo-Pinzón, G.; Patarroyo, M.A.; Patarroyo, M.E. How to combat gram-negative bacteria using antimicrobial peptides: A challenge or an unattainable goal? Antibiotics, 2021, 10(12), 1499.
[] [PMID: 34943713]
Huang, S.; Liu, H.; Liao, K.; Hu, Q.; Guo, R.; Deng, K.; Functionalized, G.O. Functionalized GO nanovehicles with nitric oxide release and photothermal activity-based hydrogels for bacteria-infected wound healing. ACS Appl. Mater. Interfaces, 2020, 12(26), acsami.0c04080.
[] [PMID: 32475108]
Huo, J.; Jia, Q.; Huang, H.; Zhang, J.; Li, P.; Dong, X.; Huang, W. Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections. Chem. Soc. Rev., 2021, 50(15), 8762-8789.
[] [PMID: 34159993]
Guan, G.; Win, K.Y.; Yao, X.; Yang, W.; Han, M.Y. Plasmonically modulated gold nanostructures for photothermal ablation of bacteria. Adv. Healthc. Mater., 2021, 10(3), 2001158.
[] [PMID: 33184997]
Chen, Y.; Gao, Y.; Chen, Y.; Liu, L.; Mo, A.; Peng, Q. Nanomaterials-based photothermal therapy and its potentials in antibacterial treatment. J. Control. Release, 2020, 328, 251-262.
[] [PMID: 32889053]
Sun, Y.; Ogawa, R.; Xiao, B.H.; Feng, Y.X.; Wu, Y.; Chen, L.H.; Gao, X.H.; Chen, H.D. Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies. Int. Wound J., 2020, 17(2), 285-299.
[] [PMID: 31724831]
Feng, Y.; Coradi Tonon, C.; Ashraf, S.; Hasan, T. Photodynamic and antibiotic therapy in combination against bacterial infections: efficacy, determinants, mechanisms, and future perspectives. Adv. Drug Deliv. Rev., 2021, 177, 113941.
[] [PMID: 34419503]
Jia, Q.; Song, Q.; Li, P.; Huang, W. Rejuvenated photodynamic therapy for bacterial infections. Adv. Healthc. Mater., 2019, 8(14), 1900608.
[] [PMID: 31240867]
Gong, M.; Xiao, J.; Li, H.; Hai, L.; Yang, K.; Li, J.; Wang, Z.; Deng, L.; He, D. Magnetically retained and glucose-fueled hydroxyl radical nanogenerators for H2O2-self-supplying chemodynamic therapy of wound infections. Mater. Sci. Eng. C, 2021, 131, 112522.
[] [PMID: 34857301]
Suryavanshi, V.S.; Maharana, T.; Jagtap, P.K. Microencapsulation of Cassia fistula Flower Extract with Chitosan and its Antibacterial Studies. Curr. Drug Deliv., 2022, 19(9), 980-990.
Lee, H.J.; Lee, D.G. Urgent need for novel antibiotics in Republic of Korea to combat multidrug-resistant bacteria. Korean J. Intern. Med., 2022, 37(2), 271-280.
[] [PMID: 35272440]
Minhas, M.U.; Ahmad, S.; Khan, K.U.; Sohail, M.; Abdullah, O.; Khalid, I.; Malik, N.S. Synthesis and Evaluation of Polyethylene Glycol-4000-Co-Poly (AMPS) Based Hydrogel Membranes for Controlled Release of Mupirocin for Efficient Wound Healing. Curr. Drug Deliv., 2022, 19(10), 1102-1115.
Kumar, S.; Mollo, A.; Kahne, D.; Ruiz, N. The bacterial cell wall: From lipid II flipping to polymerization. Chem. Rev., 2022, 122(9), 8884-8910.
[] [PMID: 35274942]
Wang, L.; Yang, J.; Yang, X.; Hou, Q.; Liu, S.; Zheng, W.; Long, Y.; Jiang, X. Mercaptophenylboronic acid-activated gold nanoparticles as nanoantibiotics against multidrug-resistant bacteria. ACS Appl. Mater. Interfaces, 2020, 12(46), 51148-51159.
[] [PMID: 33155812]
Zheng, J.; Hu, R.; Yang, Y.; Wang, Y.; Wang, Q.; Xu, S.; Yao, P.; Liu, Z.; Zhou, J.; Yang, J.; Bao, Y.; Zhang, D.; Shen, W.; Zhou, Z. Antibiotic-loaded reactive oxygen species-responsive nanomedicine for effective management of chronic bacterial prostatitis. Acta Biomater., 2022, 143, 471-486.
[] [PMID: 35259516]
Wang, Y.; Yuan, Q.; Feng, W.; Pu, W.; Ding, J.; Zhang, H.; Li, X.; Yang, B.; Dai, Q.; Cheng, L.; Wang, J.; Sun, F.; Zhang, D. Targeted delivery of antibiotics to the infected pulmonary tissues using ROS-responsive nanoparticles. J. Nanobiotechnology, 2019, 17(1), 103.
[] [PMID: 31581948]
Yung, D.B.Y.; Sircombe, K.J.; Pletzer, D. Friends or enemies? The complicated relationship between Pseudomonas aeruginosa and Staphylococcus aureus. Mol. Microbiol., 2021, 116(1), 1-15.
[] [PMID: 33576132]
Bryskier, A. Roxithromycin: Review of its antimicrobial activity. J. Antimicrob. Chemother., 1998, 41(Suppl. B), 1-21.
Huang, R.; Hu, J.; Qian, W.; Chen, L.; Zhang, D. Recent advances in nanotherapeutics for the treatment of burn wounds. Burns Trauma, 2021, 9, tkab026.
[] [PMID: 34778468]
DiPersio, C.M.; Zheng, R.; Kenney, J.; Van De Water, L. Integrin-mediated regulation of epidermal wound functions. Cell Tissue Res., 2016, 365(3), 467-482.
[] [PMID: 27351421]
Fu, X.; Li, X.; Cheng, B.; Chen, W.; Sheng, Z. Engineered growth factors and cutaneous wound healing: Success and possible questions in the past 10 years. Wound Repair Regen., 2005, 13(2), 122-130.
[] [PMID: 15828936]
Zawani, M.; Fauzi, M.B. Epigallocatechin Gallate: The emerging wound healing potential of multifunctional biomaterials for future precision medicine treatment strategies. Polymers, 2021, 13(21), 3656.
[] [PMID: 34771213]
Ran, X.; Du, Y.; Wang, Z.; Wang, H.; Pu, F.; Ren, J.; Qu, X. Hyaluronic acid-templated Ag Nanoparticles/graphene oxide composites for synergistic therapy of bacteria infection. ACS Appl. Mater. Interfaces, 2017, 9(23), 19717-19724.
[] [PMID: 28534395]
Qian, W.; Yan, C.; He, D.; Yu, X.; Yuan, L.; Liu, M.; Luo, G.; Deng, J. pH-triggered charge-reversible of glycol chitosan conjugated carboxyl graphene for enhancing photothermal ablation of focal infection. Acta Biomater., 2018, 69, 256-264.
[] [PMID: 29374599]
Zhang, D.; Wei, Y.; Chen, K.; Zhang, X.; Xu, X.; Shi, Q.; Han, S.; Chen, X.; Gong, H.; Li, X.; Zhang, J. Biocompatible reactive oxygen species (ROS)-responsive nanoparticles as superior drug delivery vehicles. Adv. Healthc. Mater., 2015, 4(1), 69-76.
[] [PMID: 25147049]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy