Peptides are small biological molecules of interest in drug delivery for applications including therapeutics, molecular building blocks, and cell-targeted ligands. A feature of interest in pharmacology development is that some peptides exhibit antimicrobial activity, which can be useful to tackle the growing global concern of microbial resistance to conventional antibiotics. However, these antimicrobial molecules, as well as other biomacromolecules, are difficult to administer orally due to the harsh conditions of the gastrointestinal tract and low penetration into the intestinal mucosa. Intravenous administration shows also low efficiency given the rapid proteolytic degradation in the bloodstream. As a result, the development of carriers for antimicrobial peptides and other biomolecules has attracted increased attention in recent years. The topical application of antimicrobial agents offers excellent potential for low invasive treatments, given the possibility of using precisely delivered and more concentrated bioactive molecules on the desired target. These topical systems can improve bioavailability, as well as provide precise distribution and adequate pharmacokinetics with reduced toxicological effects. In addition, they ensure protection against chemical agents and enzymatic degradation. Polymer-based hydrogels are of particular interest because they are primarily hydrophilic, can generate three-dimensional matrices, are mainly composed of water, and allow loading labile antimicrobial molecules and antibiotics. Here, we propose a formulation based on a polymeric matrix composed of gelatin (0.7, 1.1, and 1.5% w/v) and polyvinyl alcohol (0.1, 0.4, and 0.7% w/v). Additionally, we plan to improve the stability of the antimicrobial peptides even further by immobilization on nanostructured materials such as magnetite, collagen, and chitosan nanoparticles. The obtained topicals show remarkable stability (more than 30 days under accelerated aging conditions), pseudoplastic rheological behavior, ease of applicability, compressibility, and cohesiveness upon application. We are currently working on dispersing the free and immobilized peptides and on conducting biocompatibility assays (e.g., cytotoxicity, hemolysis, and platelet aggregation).

Formulation and characterization of biocompatible hydrogels for the encapsulation of antimicrobial peptides as a topical treatment for the control of skin infections

ACS Fall 2021

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