Alkylated poly(l-lysine citramide) as models to investigate the ability of amphiphilic macromolecular drug carriers to physically entrap lipophilic compounds in aqueous media

Poly(l-lysine citramide) was synthesized to serve as a polymeric bioresorbable drug carrier. It was previously shown that low molecular weight poly(l-lysine citramide) hydrophobized with heptyl and lauryl side chains (PLCA-C7p with p=43 and 60%; and PLCA-C12p, with p=68, 75 and 100%) formed aggregates in aqueous media. The size of these aggregates was found to depend on the balance between repulsive electrostatic charges and attractive hydrophobic interactions, on the degree of ionization, and on the ionic strength. In this paper, the formation of these aggregates was further investigated by fluorescence probing, using two polarity sensitive molecules, pyrene and Nile Red, which were physically entrapped within the lipophilic core of the aggregates. In contrast to other micellar structures formed by surfactants and amphiphilic block copolymers, aggregates were observed even at very low polymer concentrations. The capacity of the hydrophobic domains to accommodate lipophilic molecules via physical entrapment was demonstrated with progesterone.