Self-assembly of β-alanine homotetramer: formation of nanovesicles for drug delivery

Abstract

The present paper describes the fabrication of nanovesicles using the stirring induced self-assembly of a β-alanine homotetramer (H₂N–βAla–βAla–βAla–βAla–CONH₂) in an aqueous medium. Dynamic light scattering (DLS) studies revealed the formation of nanostructures with an average particle size of ∼463 nm. The morphology and size of the nanostructures was also confirmed by electron microscopy. The formation of well-defined spherical nanovesicles in the size range of ∼100 nm to 250 nm is displayed. Secondary structure estimations using circular dichroism (CD) and infrared spectroscopic (IR) studies suggest an intramolecularly hydrogen bonded conformation for the tetrapeptide. CD and IR studies conducted in an aqueous medium before and after self-assembly depict a significant change in structure and hydrogen bonding patterns. Supportive evidence regarding the conformation of the tetrapeptide is provided by the conformational search using computational methods. The theoretically predicted minimum energy structure depicts an 8-helix type of backbone folding with the formation of two 8-membered intramolecularly hydrogen bonded rings. Four of the short helical type strands of the tetrapeptide were then subjected to a geometry optimization that resulted in the formation of an assembly with a central cavity, completely in agreement with experimental findings. Finally these nanovesicles were evaluated for their potential use as carriers of the potent anti-Parkinson's drug L-DOPA. We have observed that in aqueous media these nanovesicles are able to encapsulate the L-DOPA molecules, indicated by DLS measurements and also by absorption and emission spectroscopic methods. By lowering the pH to 6.2 these loaded vesicles are able to release the drug slowly. These assemblies thus can be considered as potential delivery vehicles for L-DOPA which normally suffers from poor administration.