Understanding the adsorption of salmon calcitonin, antimicrobial peptide AP114 and polymyxin B onto lipid nanocapsules

The adsorption of therapeutic molecules, e.g., peptides, onto nanocarriers is influenced by the properties of the carrier, adsorbed molecule and continuous phase. Hence, through changes in the composition of the nanocarrier and the medium, it should be possible to tune the system to make it capable of efficiently adsorbing peptides. The adsorption of calcitonin, antimicrobial peptide AP114 and polymyxin B onto lipid nanocapsules was investigated. The adsorption data were fitted to a Langmuir isotherm. Dynamic light scattering and laser Doppler velocimetry were used to investigate the changes in the hydrodynamic diameter and zeta potential, respectively, of the nanocarrier. The peptide adsorption was primarily governed by electrostatic forces; however, even without the presence of an ionisable surfactant, a significant amount of each tested molecule was adsorbed due to the enormous surface area of the nanocarriers and to peptide-nanocarrier interactions. The addition of an ionisable lipophilic surfactant, lecithin, improved the adsorption yield, which reached values of up to 100%. The adsorption yield and the properties of the nanocarrier, particularly the zeta potential, depended on the carrier and peptide concentrations and their mixing ratio. The adsorption of all tested molecules obeyed the Langmuir model over a limited concentration range

Lipid-based nanoformulations for peptide delivery

Nanoformulations have attracted a lot of attention because of their size-dependent properties. Among the array of nanoformulations, lipid nanoformulations (LNFs) have evoked increasing interest because of the advantages of their high degree of biocompatibility and versatility. The performance of lipid nanoformulations is greatly influenced by their composition and structure. Therapeutic peptides represent a growing share of the pharmaceutical market. However, the main challenge for their development into commercial products is their inherent physicochemical and biological instability. Important peptides such as insulin, calcitonin and cyclosporin A have been incorporated into LNFs. The association or encapsulation of peptides within lipid-based carriers has shown to protect the labile molecules against enzymatic degradation. This review describes strategies used for the formulation of peptides and some methods used for the assessment of association efficiency. The advantages and drawbacks of such carriers are also described

Reverse micelle-lipid nanocapsules: a novel strategy for drug delivery of the plectasin derivate AP138 antimicrobial peptide

Introduction: Resistance to traditional antibiotics is an increasingly serious problem. Antimicrobial peptides (AMPs) have emerged as a new therapeutic class with great potential against infectious diseases, as they are less prone to induce resistance. Nanotechnology-based delivery strategies can improve the efficiency and stability of AMPs, particularly against proteolytic degradation. Lipid nanocapsules (LNCs) are a new generation of biomimetic nanocarriers and were used in this study to deliver peptides. Methods: AMP-loaded reverse micelles (RM) were developed and incorpo rated into LNCs by the phase inversion process and the antimicrobial activity of the AMPs-loaded LNC was evaluated by the minimum inhibitory concentration method. We studied the activity of AMP solutions and AMP-loaded LNCs against Gram-positive and Gram-negative bacterial strains and then evaluated the encapsulation of a new cationic AMP called AP138. Finally, we analyzed the effect of enzymatic attack on AP138 and AP138-RM-LNCs after incubation with trypsin. Results: AP138 was efficiently encapsulated in the LNCs (encapsulation efficiency = 97.8% at a drug loading of 0.151%), resulting in protection against degradation by proteases and the preservation of antimicrobial activity against , including . Conclusion: This study shows that RM-LNCs are an excellent candidate system to deliver AMPs

Synergistic interactions between antimicrobial peptides derived from plectasin and lipid nanocapsules containing monolaurin as a cosurfactant against Staphylococcus aureus

Anita Umerska,1 Viviane Cassisa,2 Guillaume Bastiat,1 Nada Matougui,1 Hassan Nehme,1 Florence Manero,3 Matthieu Eveillard,4 Patrick Saulnier1 1MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, Cedex, France; 2Laboratoire de bactériologie, CHU Angers, France; 3SCIAM (Service Commun d’Imagerie et d’Analyses Microscopiques), Angers, France; 4Equipe ATIP AVENIR, CRCINA, Inserm, Université de Nantes, Université d’Angers, Angers, France Abstract: Development of effective antibacterial agents for the treatment of infections caused by Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), is an area of intensive research. In this work, the antibacterial efficacy of two antimicrobial peptides derived from plectasin, AP114 and AP138, used alone and in combination with monolaurin-lipid nanocapsules (ML-LNCs) was evaluated. Several interesting findings emerged from the present study. First, ML-LNCs and both plectasin derivatives showed potent activity against all 14 tested strains of S. aureus, independent of their resistance phenotype. Both peptides displayed a considerable adsorption (33%–62%) onto ML-LNCs without having an important impact on the particle properties such as size. The combinations of peptide with ML-LNC displayed synergistic effect against S. aureus, as confirmed by two methods: checkerboard and time-kill assays. This synergistic interaction enables a dose reduction and consequently decreases the risk of toxicity and has the potential of minimizing the development of resistance. Together, these results suggest that ML-LNCs loaded with a plectasin derivative may be a very promising drug delivery system for further development as a novel antibacterial agent against S. aureus, including MRSA. Keywords: nanoparticles, antimicrobial peptides, glycerol monolaurate, synergy, antibiotic resistance, MRSA, methicillin-resistant Staphylococcus aureu