Publicação
Polymeric micelles for delivery of antimicrobial peptides
| Resumo: | Antimicrobial resistance is one of the most serious threats to human health in this century, causing significant economic burden and high mortality. Without effective antimicrobial therapies, the number of deaths associated with infections will continue to rise inexorably. This prospect has prompted the search for therapeutic alternatives, such as antimicrobial peptides (AMPs). However, non-specific toxicity, low stability and short half-life hinder the development of AMPs into stand-alone medicines, limiting their potential as powerful antimicrobial agents. These challenges can be overcome by utilizing novel formulation strategies, such as nanogels or polymeric micelles for the delivery of such peptides. In this project, oleic-grafted hyaluronan (OL-HA) polymeric micelles for the encapsulation of the antimicrobial cell penetration peptides L- and D-PenetraMax and its lipidated version Syn-2 were developed and characterized. With the optimized method, it was possible to prepare small anionic micelles, with a hydrodynamic diameter range of 100 – 300 nm, capable of efficiently loading all three peptides. High values of encapsulation efficiency were found but at the expense of a slower release profile. L-PenetraMax showed to be very prone to degradation and its encapsulation did not improve this behaviour. The polymeric micelles, despite the very slow release, effectively reduced the peptide cytotoxicity towards hepatic, endothelial, intestinal and red blood cells (RBCs), while maintaining their antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, the polymeric micelles prepared also seemed capable of prevent biofilm growth at concentrations higher than the minimal inhibitory concentration (MIC) values. These findings support the use of OL-HA polymeric micelles to increase the safety of peptides with antimicrobial properties to intravenous administration. |
|---|---|
| Autores principais: | Cunha, Cristiana Filipa Barreiro da |
| Assunto: | Oleic-grafted hyaluronan Polymeric micelles Cell-penetrating peptides Antimicrobial peptides Hialuronato oleico Nanopartículas poliméricas Péptidos de penetração celular Péptidos antimicrobiais |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| Resumo: | Antimicrobial resistance is one of the most serious threats to human health in this century, causing significant economic burden and high mortality. Without effective antimicrobial therapies, the number of deaths associated with infections will continue to rise inexorably. This prospect has prompted the search for therapeutic alternatives, such as antimicrobial peptides (AMPs). However, non-specific toxicity, low stability and short half-life hinder the development of AMPs into stand-alone medicines, limiting their potential as powerful antimicrobial agents. These challenges can be overcome by utilizing novel formulation strategies, such as nanogels or polymeric micelles for the delivery of such peptides. In this project, oleic-grafted hyaluronan (OL-HA) polymeric micelles for the encapsulation of the antimicrobial cell penetration peptides L- and D-PenetraMax and its lipidated version Syn-2 were developed and characterized. With the optimized method, it was possible to prepare small anionic micelles, with a hydrodynamic diameter range of 100 – 300 nm, capable of efficiently loading all three peptides. High values of encapsulation efficiency were found but at the expense of a slower release profile. L-PenetraMax showed to be very prone to degradation and its encapsulation did not improve this behaviour. The polymeric micelles, despite the very slow release, effectively reduced the peptide cytotoxicity towards hepatic, endothelial, intestinal and red blood cells (RBCs), while maintaining their antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, the polymeric micelles prepared also seemed capable of prevent biofilm growth at concentrations higher than the minimal inhibitory concentration (MIC) values. These findings support the use of OL-HA polymeric micelles to increase the safety of peptides with antimicrobial properties to intravenous administration. |
|---|