Ibuprofen loading and release in amphiphilic peptide FA32 and its derivatives: a coarse-grained molecular dynamics simulation study

Abstract

A molecular dynamics simulation study is reported to investigate the loading and release of ibuprofen (IBU) in amphiphilic peptide (AF)6H5K15 (FA32) and its derivatives (F12H5K15 and F16H5K15). The peptides are represented by the MARTINI coarse-grained model, and a similar model is developed here for IBU. Upon the loading of IBU in FA32, quasi-spherical core/shell structured micelles are formed. IBU is predominantly located in the hydrophobic core and covered by Phe and Ala residues, while Lys is in the hydrophilic shell. With increasing concentration of IBU, the micelles become larger due to increased hydrophobic interactions. In FA32 derivatives, the loading of IBU leads to different morphologies; particularly, a well-structured nanofibre is formed in F16H5K15. Upon pH change, the release of IBU from FA32 micelles is found to be slower than from F16H5K15 nanofibre, suggesting the former is better in controlled release. The simulation study reveals that IBU-loaded morphology can be altered by changing the type of peptide and has a significant effect on IBU release profile. This bottom-up insight might be useful in the rational design of carriers for efficient drug loading and release.