TY - JOUR
T1 - Dhvar5-chitosan nanogels and their potential to improve antibiotics activity
AU - Costa, B.
AU - Alves, P. M.
AU - Fonseca, D. R.
AU - Campos, F.
AU - Monteiro, A. C.
AU - Shahrour, H.
AU - Gomes, A.
AU - Costa, F.
AU - Gomes, P.
AU - Martínez-de-Tejada, G.
AU - Monteiro, C.
AU - Martins, M. C. L.
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/10
Y1 - 2024/10
N2 - Infection is one of the main causes of orthopedic implants failure, with antibiotic-resistant bacteria playing a crucial role in this outcome. In this work, antimicrobial nanogels were developed to be applied in situ as implant coating to prevent orthopedic-device-related infections. To that regard, a broad-spectrum antimicrobial peptide, Dhvar5, was grafted onto chitosan via thiol–norbornene “photoclick” chemistry. Dhvar5-chitosan nanogels (Dhvar5-NG) were then produced using a microfluidic system. Dhvar5-NG (1010 nanogels (NG)/mL) with a Dhvar5 concentration of 6 μg/mL reduced the burden of the most critical bacteria in orthopedic infections - methicillin-resistant Staphylococcus aureus (MRSA) – after 24 h in medium supplemented with human plasma proteins. Transmission electron microscopy showed that Dhvar5-NG killed bacteria by membrane disruption and cytoplasm release. No signs of cytotoxicity against a pre-osteoblast cell line were verified upon incubation with Dhvar5-NG. To further explore therapeutic alternatives, the potential synergistic effect of Dhvar5-NG with antibiotics was evaluated against MRSA. Dhvar5-NG at a sub-minimal inhibitory concentration (109 NG/mL) demonstrated synergistic effect with oxacillin (4-fold reduction: from 2 to 0.5 μg/mL) and piperacillin (2-fold reduction: from 2 to 1 μg/mL). This work supports the use of Dhvar5-NG as adjuvant of antibiotics to the prevention of orthopedic devices-related infections.
AB - Infection is one of the main causes of orthopedic implants failure, with antibiotic-resistant bacteria playing a crucial role in this outcome. In this work, antimicrobial nanogels were developed to be applied in situ as implant coating to prevent orthopedic-device-related infections. To that regard, a broad-spectrum antimicrobial peptide, Dhvar5, was grafted onto chitosan via thiol–norbornene “photoclick” chemistry. Dhvar5-chitosan nanogels (Dhvar5-NG) were then produced using a microfluidic system. Dhvar5-NG (1010 nanogels (NG)/mL) with a Dhvar5 concentration of 6 μg/mL reduced the burden of the most critical bacteria in orthopedic infections - methicillin-resistant Staphylococcus aureus (MRSA) – after 24 h in medium supplemented with human plasma proteins. Transmission electron microscopy showed that Dhvar5-NG killed bacteria by membrane disruption and cytoplasm release. No signs of cytotoxicity against a pre-osteoblast cell line were verified upon incubation with Dhvar5-NG. To further explore therapeutic alternatives, the potential synergistic effect of Dhvar5-NG with antibiotics was evaluated against MRSA. Dhvar5-NG at a sub-minimal inhibitory concentration (109 NG/mL) demonstrated synergistic effect with oxacillin (4-fold reduction: from 2 to 0.5 μg/mL) and piperacillin (2-fold reduction: from 2 to 1 μg/mL). This work supports the use of Dhvar5-NG as adjuvant of antibiotics to the prevention of orthopedic devices-related infections.
KW - Antimicrobial peptides
KW - Chitosan nanoparticles
KW - Thiol−ene click chemistry
KW - Piperacillin
KW - Oxacillin
KW - Synergistic effect
UR - http://www.scopus.com/inward/record.url?scp=85199501379&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2024.134059
DO - 10.1016/j.ijbiomac.2024.134059
M3 - Article
C2 - 39038581
AN - SCOPUS:85199501379
SN - 0141-8130
VL - 277
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
M1 - 134059
ER -