The potential of antimicrobial peptides conjugated onto nano fibrillated cellulose for chronic wound treatment
2022 (English)Independent thesis Advanced level (degree of Master (Two Years)), 30 credits / 45 HE credits
Student thesis
Abstract [en]
Antibiotics have been a pivotal pharmaceutical compound since their discovery in the early 20th century. Misuse of antibiotics in multiple sectors within our society has allowed antibiotic-resistant bacteria to arise and shortly commercial antibiotics could be rendered ineffective for treatment. Antimicrobial peptides (AMPs) are novel antimicrobial treatment options that could be used as a substitute for commercial antibiotics. Herein AMPs based on the KR-12 sequence, the active region of the human cathelicidin host defense peptide LL-37, have been investigated for the purpose to treat chronic wound bacterial infections. The two main AMPs for the current project are, one KR-12 monomer with an optimized sequence called KR12-Q5KD9A-CYS and one KR12 dimer utilizing a Glycine-proline linker named CD4-PP. Both monomer and dimerAMPs were conjugated onto nano-fibrillated cellulose (NFC) using thiol chemistry resulting in an ointment-like formulation which is referred to as PBF-10 and PBF-11 respectively. Antimicrobial activity, stability, and liposome leakage were assessed, and the result showed high antimicrobial activity, and liposome leakage capacity for both PBF-10 and PBF-11however PBF-11 seems to be more stable in serum. These results display the potential of utilizing CNF together with AMPs, preferably the dimeric CD4PP peptide, to address chronic wound infections and simultaneously alleviate selective pressure causing antibiotic resistance. Not only would an ointment-like formulation be suitable for local applications but the added stability whilst retaining the vital functions of the AMP is critical for proper healing of the wound. This current work could be used in the future as an intermediate to optimize the characteristics of both CNF and AMPs. For example, conjugation of the cyclic variant ofCD4PP, which already has shown to be more stable than its linear counterpart, could be synthesized to evaluate the synergistic effect of both cyclization and CNF conjugation.
Place, publisher, year, edition, pages
2022. , p. 27
Keywords [en]
LL-37, KR-12, antibiotic, antibiotic resistance, wound, chronic wound, Nanofibrillated cellulose, NFC, CNF, CD4-PP, Antimicrobial peptide, AMP
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-481339OAI: oai:DiVA.org:uu-481339DiVA, id: diva2:1686455
Subject / course
Pharmaceutical Biosciences
Educational program
Master Programme in Drug Discovery and Development
Supervisors
Examiners
2022-08-102022-08-092022-08-10Bibliographically approved