SELF-ASSEMBLY AND DRUG DELIVERY IN AMPHIPHILIC PEPTIDES: MICROSCOPIC INSIGHTS FROM COARSE-GRAINED SIMULATIONS

Abstract

Amphiphilic peptides are biodegradable and biocompatible, important characteristics for ideal drug carriers. They can form nano-sized micelles with hydrophobic cores allowing for encapsulation of hydrophobic drugs. Through molecular dynamics simulation, we investigated amphiphilic peptides to quantitatively understand the self-assembly behavior of amphiphilic peptides from a microscopic scale, elucidate the detailed process of drug loading and release, and provide bottom-up guidelines towards the intelligent design of new amphiphilic peptides for drug delivery. We studied short amphiphilic peptides FmDn and FmKn self-assembly. For an optimal ratio of hydrophobic/hydrophilic residues of 3/4 for both F3Kn and F6Kn, quasi-spherical micelles are formed. Further we studied a relatively longer peptide FA32 [(AF)6H5K15] and its derivatives self-assembly. With increasing hydrophilic components the assembly capability is reduced and with increasing hydrophobic residues the formation of fiber-like structures is observed. A sample hydrophobic drug, ibuprofen (IBU), is investigated for loading and release. Upon the loading of IBU in FA32, quasi-spherical core/shell structured micelles are formed. In F16H5K15, however, the loading of IBU leads to a well-structured nanofiber. The release of IBU from FA32 micelles is slower than from F16H5K15 nanofiber, suggesting the former is better in controlled release.