Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance

Abstract

<jats:p>Antimicrobial peptides (AMPs), otherwise known as host defence peptides (HDPs), are naturally occurring biomolecules expressed by a large array of species across the phylogenetic kingdoms. They have great potential to combat microbial infections by directly killing or inhibiting bacterial activity and/or by modulating the immune response of the host. Due to their multimodal properties, broad spectrum activity, and minimal resistance generation, these peptides have emerged as a promising response to the rapidly concerning problem of multidrug resistance (MDR). However, their therapeutic efficacy is limited by a number of factors, including rapid degradation, systemic toxicity, and low bioavailability. As such, many strategies have been developed to mitigate these limitations, such as peptide modification and delivery vehicle conjugation/encapsulation. Oftentimes, however, particularly in the case of the latter, this can hinder the activity of the parent AMP. Here, we review current delivery strategies used for AMP formulation, focusing on methodologies utilized for targeted infection site release of AMPs. This specificity unites the improved biocompatibility of the delivery vehicle with the unhindered activity of the free AMP, providing a promising means to effectively translate AMP therapy into clinical practice.</jats:p>

Peptides with Dual Antimicrobial–Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides

“…Peptide conjugation consists of peptide sticking, that is, the addition of polymers, such as poly(lactic-co-glycolic acid), polyvinylpyrrolidone, and polyethylene glycol, to peptides, which contributes to an improvement in bioavailability and an increase in half-life. It can also help prevent immune response and protect against degradation [ 10 , 23 ].…”

“… Peptide limitations and how to overcome them. [ 10 , 22 , 23 , 26 , 27 ]. On the left side there are four limitations to working with peptides which are in red.…”

Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria

“…This led us to explore bioconjugation and formulation strategies in order to mitigate these negative effects [4,60,71]. For an extensive review on these strategies, the reader is invited to consult [64] and references therein.…”

“…Alternative approaches to minimize proteolytic cleavage include producing synthetic AMPs that incorporate D-amino acids [60], β-amino acids [61], and other non-natural amino acids [62]. The topic of improving in vivo stability has been extensively reviewed elsewhere [4,63,64], and it will not be discussed further here. In terms of toxicity, some studies have shown that the introduction of D-amino acids or the rational optimization of amphipathicity can help in lowering host toxicity [60,[65][66][67].…”

“…Some studies have shown that enriching AMPs with Arg/Trp residues results in peptides with increased bioavailability [70]. Alternatively, the conjugation of AMPs with different polymers [71,72] or encapsulation in pegylated micelles [60] has been proposed as a feasible option to increase bioavailability [64].…”