Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E.

Area of Science:

• Biomaterials Science
• Pharmaceutical Sciences
• Infectious Diseases

Background:

• Polymyxins are crucial antibiotics against multidrug-resistant (MDR) pathogens.
• Poor in vivo stability necessitates high doses, leading to toxicity.
• Advanced drug delivery systems are needed to improve polymyxin therapy.

Purpose of the Study:

• To develop and characterize nanoparticle-based delivery systems for polymyxins B and E.
• To evaluate the stability, drug loading, release kinetics, and in vitro efficacy of these nanoformulations.
• To assess the potential of these nanoparticles to overcome polymyxin limitations.

Main Methods:

• Self-assembly of amphiphilic poly(l-glutamic acid-co-d-phenylalanine) [P(Glu-co-dPhe)] into nanoparticles.
• Characterization of nanoparticles: size, surface charge, stability, cytotoxicity, and macrophage uptake.
• Determination of encapsulation efficiency and drug loading for polymyxins B and E.
• In vitro release studies in buffer and human blood plasma, analyzed with mathematical models.
• Determination of minimal inhibitory concentrations (MICs) for nanoformulations and free antibiotics.

Main Results:

• Successfully developed P(Glu-co-dPhe) nanoparticles capable of encapsulating polymyxins B and E.
• Characterization confirmed nanoparticle stability, controlled drug release profiles, and reduced cytotoxicity.
• Nanoformulations demonstrated potent antimicrobial activity, comparable to free antibiotics, against MDR pathogens.
• Drug release kinetics varied between buffer and plasma, indicating potential for controlled in vivo release.

Conclusions:

• P(Glu-co-dPhe) nanoparticles represent a promising delivery system for polymyxins.
• This nanoformulation strategy can enhance polymyxin stability and therapeutic efficacy.
• The developed system offers a potential solution to overcome polymyxin toxicity and improve treatment outcomes for MDR infections.