Self-aggregation of amphiphilic poly(L-aspartic acid) derivatives and methotrexate delivery

Abstract

In this study, synthesis and characterization of biodegradable poly(aspartic acid) was carried out with or without grafted long alkyl groups of different chain length for preparing self-aggregates. Effect of grafted long alkyl groups on self-aggregation behavior was investigated using various experimental methods. The self-aggregates incorporated with methotrexate by physical loading and chemical conjugation was characterized, and the interaction of modified poly(aspartic acid) with lipid bilayer was also studied by Langmuir-Blodgett method. Poly(aspartic acid) grafted with long alkyl groups was synthesized from acid-catalyzed polycondensation of L-aspartic acid to give poly(succinimide), followed by hydrolysis and aminolysis by alkylamine. Poly(aspartic acid) grafted with alkyl group formed self-aggregates from milky suspension by the sonication method. The alkyl chain length and the grafting amount of alkyl groups influenced the properties of hydrophobic microdomains such as hydrophobicity, polarization, and aggregation number. The overall aggregate structure and properties such as aggregate size, CAC, stability, and chain conformation were directly dependent upon the property of hydrophobic microdomains. The more grafting amount of alkyl groups and longer alkyl chain length induced the more stable and compact self-aggregates. Extended chain conformation was forced to have compact structure by strong association of grafted alkyl groups as the degree of substitution increased. One self-aggregate was composed of several hydrophobic microdomains and the number of hydrophobic microdomains was linearly dependent upon the degree of substitution. Poly(aspartic acid) grafted with octadecyl chain existed as only self-aggregate in room temperature, whereas that with hexadecyl and dodecyl chains behaved like polymeric surfactant due to higher chain flexibility. Self-aggregates based on poly(2-hydroxyethyl aspartamide) grafted with octadecyl groups was used for methotrex...