Mono- and Bivalent Poly(iso-butylene)-Alanines for Drug-Delivery of Nimodipine and Triamcinolone Acetonide

Poly-iso-butylene (PIB) is a well known biocompatible polymer with application as a solid drug delivery system. However its applications are limited by its soft mechanical properties, necessitating the introduction of assembling structural elements to modify its microstructure by reinforcing elements to achieve structural stability. We here investigate the impact of embedded oligo-alanine-units (Ala) to induce beta-sheets and the release of drugs from a so solidified PIB, prepared by living carbocationic polymerization (LCCP). Mono- (PIB-Ala₂-Ac, 12,2 kDa) and bivalent PIB-polymers (PIB-(Ala₂-Ac)₂, 16,7 kDa) with attached oligo(alanines) as endgroups were synthesized and induce beta-sheets to adjust the mechanical strength of these biomaterials. Mechanical and thermal properties are investigated using temperature dependent IR spectroscopy and melt-rheology rheology, with circular dichroism (CD) proving the formation of stable beta-sheets for PIB-(Ala₂-Ac)₂ inside the solid polymer. Two drugs, nimodipine and triamcinolone acetonide, are incorporated into different PIB matrices to study the influence of drug-secondary structure interactions. The polymer/drug formulations display a stable release of the drugs over a period of 42 days into a PBS buffer, thus presenting an attractive material for long-term targeted release with adjustable mechanical properties.