Stability and acidic pH-mediated leakage of guest molecules from self-assembly of poly(amidoamine)-graft-alkyl copolymers

Abstract

Self-assembly of a copolymer with compact hydrophobic core, good stability at physiological condition and responsive nature towards stimuli is beneficial for sustained release application. Diffusion mediated release from a self-assembly at normal physiological conditions limits its application. Herein, extremely simple self-assemblies of poly(amidoamine)-graft-alkyl (PAMAM-g-alkyl) copolymers have been designed based on the N-alkylation (alkyl = C-8, C-10, C12, and C-18) of linear PAMAM to elucidate the differences in properties of the hydrophobic core and to select the appropriate self-assembly for triggered release application. The synthesis of PAMAM-g-alkyl copolymers allows us to assess the influence of alkyl chain length on the critical micelle concentration, stability, core hydrophobicity, core compactness, and encapsulation-release performance of the self-assemblies. The C18 chains facilitate the formation of compact micellar core with higher hydrophobicity, higher encapsulation property, and extended stability at pH 7.4. The C18 bearing micelles showed lowest (20–26% w/w) release of guest molecules at pH 7.4 while triggered the release (65–80% w/w) at pH 5. The triggered release behavior of the self-assembly is attributed to the leakage of guest molecules through partial dissociation of the copolymer chains followed by the creation of release channel. The effect of alkyl chain length on the micellar stability was further probed by Förster Resonance Energy Transfer (FRET) between two hydrophobic chromophores. The design of this type of simple self-assembly is beneficial to encapsulate hydrophobic guest molecules for sustained release application.