RESUMO
Antimicrobial peptide LL37 is a promising antibacterial candidate due to its potent antimicrobial activity with no known bacterial resistance. However, intrinsically LL37 is susceptible to degradation in wound fluids limits its effectiveness. Bacterial toxins which are released after cell lysis are found to hinder wound healing. To address these challenges, encapsulating LL37 in microspheres (MS) and loading the MS onto activated carbon (AC)-chitosan (CS) hydrogel. This advanced wound dressing not only protects LL37 from degradation but also targets bacterial toxins, aiding in the healing of chronic wound infections. First, LL37 MS and LL37-AC-CS hydrogel were prepared and characterised in terms of physicochemical properties, drug release, and peptide-polymer compatibility. Antibacterial and antibiofilm activity, bacterial toxin elimination, cell migration, and cell cytotoxicity activities were investigated. LL37-AC-CS hydrogel was effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. LL37-AC-CS hydrogel bound more endotoxin than AC with CS hydrogel alone. The hydrogel also induced cell migration after 72 h and showed no cytotoxicity towards NHDF after 72 h of treatment. In conclusion, the LL37-AC-CS hydrogel was shown to be a stable, non-toxic advanced wound dressing method with enhanced antimicrobial and antitoxin activity, and it can potentially be applied to chronic wound infections to accelerate wound healing.
Assuntos
Antibacterianos , Bandagens , Quitosana , Escherichia coli , Hidrogéis , Microesferas , Pseudomonas aeruginosa , Staphylococcus aureus , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Hidrogéis/química , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/prevenção & controle , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Catelicidinas , Testes de Sensibilidade Microbiana/métodos , Toxinas Bacterianas , Liberação Controlada de Fármacos , Movimento Celular/efeitos dos fármacos , Carbono/química , Biofilmes/efeitos dos fármacosRESUMO
Dengue, caused by the dengue virus (DENV), is a prevalent arthropod-borne disease in humans and poses a significant burden on public health. Severe cases of dengue can be life-threatening. Although a licensed dengue vaccine is available, its efficacy varies across different virus serotypes and may exacerbate the disease in some seronegative recipients. Developing a safe and effective vaccine against all DENV serotypes remains challenging and requires continued research. Conventional approaches in dengue vaccine development, using live or attenuated microorganisms or parts of them often contain unnecessary epitopes, risking allergenic or autoimmune reactions. To address these challenges, innovative strategies such as peptide vaccines have been explored. Peptide vaccines offer a safer alternative by inducing specific immune responses with minimal immunogenic fragments. Chemical modification strategies of peptides have revolutionized their design, allowing for the incorporation of multi-epitope presentation, self-adjuvanting features, and self-assembling properties. These modifications enhance the antigenicity of the peptides, leading to improved vaccine efficacy. This review outlines advancements in peptide-based dengue vaccine development, leveraging nanoparticles as antigen-displaying platforms. Additionally, key immunological considerations for enhancing efficacy and safety against DENV infection have been addressed, providing insight into the next-generation of dengue vaccine development leveraging on peptide-nanoparticle technology.