Stimuli-Sensitive Microgels from Native Elastin: An Easy Approach for a Drug Release System

Abstract

Thermo-and pH-responsive microgels were prepared from solubilized native elastin by crosslinking of the elastin lysine residues with poly(ethylene glycol) diglycidyl ether (PEG-DGE) and with bis(sulfosuccinimidyl) suberate (BS3). In the first case, a peptide-PEG conetwork was obtained whereas, in the second case, the elastin peptides were interlinked with hydrophobic bridges. The structure of the microgels was controlled by the ratio of crosslinker to elastin and by performing the crosslinking reaction in an inverse minielemulsion, yielding particles with a diameter in the submicron range. Depending on the degree of crosslinking, the hybrid microgels exhibited a volume change transition at 37 and 35.5 C and pH responsivity in the range of 5-7 for microgels crosslinked with PEG-DE and BS3, respectively. This temperature-and pH-responsive behavior can be assigned to the well-investigated coacervation of elastin peptides, demonstrating that the elastin functionality is abolished only by rather dense crosslinking. In spite of the broad distribution in the molecular weight of the elastin molecules, the microgels remained soluble. Light scattering and sedimentation experiments demonstrated that the coacervation occurred predominantly intramolecularly, i.e., by collapse in the core while the corona stabilized the colloidal dispersion against precipitation. Preliminary experiments were conducted to evaluate the suitability of these microgels for use as a drug-release system and demonstrated

Coacervation of Elastin‐Like Recombinamer Microgels

“…Recently, (DLS) that measures the hydrodynamic radius at low concentration of microgels was used to determine the VPTT of native, α-elastin microgel. [ 5,6 ] From the obtained data it was shown that the VPTT behaviour was reversible and the fact that the native α -elastin microgels remains soluble can be explained by the heterogeneous morphology of the microgels with a predominant corona formed by water-soluble segments of amino acids. [ 5 ] It is known from the temperature sensitive synthetic microgels that, below the VPTT, they are in a swollen state, given by the dissolution of the hydrophilic groups in water through formation of hydrogen bonds.…”

“…[ 5,6 ] From the obtained data it was shown that the VPTT behaviour was reversible and the fact that the native α -elastin microgels remains soluble can be explained by the heterogeneous morphology of the microgels with a predominant corona formed by water-soluble segments of amino acids. [ 5 ] It is known from the temperature sensitive synthetic microgels that, below the VPTT, they are in a swollen state, given by the dissolution of the hydrophilic groups in water through formation of hydrogen bonds. [ 18 ] Above this temperature, water is expelled from the microgel, and the hydrophobic groups are free to interact, which leads to phase separation and collapse of the microgels.…”

“…[ 3,4 ] Recently, thermoresponsive and pH-responsive microgels were prepared from solubilized α-elastin derived from bovine neck ligament, by crosslinking of the lysine residues in elastin using the hydrophilic amine-reactive crosslinker poly(ethylene glycol) diglycidyl ether (PEG-DGE). [ 5 ] For this biohybrid microgel, information about morphological and polypeptide-water interactions in the process of volume phase temperature transition (VPTT) were obtained by dynamic light scattering (DLS) at low concentration, 1 H high-resolution magic-angle sample spinning (HRMAS), nuclear magnetic resonance (NMR) spectroscopy, and relaxometry. [ 6 ] These microgels showed a reversible phase transition for the studied fi ve cycles of heating and cooling.…”