Amphiphilic derivatives of a polyaspartamide: their aggregation and solubilization ability.Tensiometric and spectrophotometric studies

Abstract

The self-aggregation and solubilization capability of a series of amphiphilic copolymers obtained by derivatisation of polymeric chain of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) with polyethylene glycols (PEG, being different molecular weight 2000 or 5000 Da, PEG2000 and PEG5000, respectively) and/or hexadecylamine alkyl chain (C16), namely PHEA–PEG2000, PHEA–PEG5000, PHEA–C16, PHEA–PEG2000–C16 and PHEA–PEG5000–C16, have been evidenced by performing systematic tensiometric and spectrophotometric studies. All measurements have been performed at 25.0 °C over a wide copolymer concentration range. The tensiometric results have shown that, for all copolymers studied, the surface tension of the copolymer aqueous solutions significantly depends on both concentration and copolymer nature and, in particular, copolymers bearing both the hydrophilic and hydrophobic moieties PEG and C16 alkyl chain, respectively, are much more surface active than those carrying only the PEG units and are able to self-aggregate. In addition, the hydrophilic portion plays a relevant role in the self aggregation process, in fact, the critical aggregation concentration values of the copolymers significantly increase on increasing molecular weight of PEG units in the copolymers. The spectrophotometric data have evidenced that all the copolymers exert a solubilization capability towards a sparingly water soluble drug, namely Tamoxifen (TAM), which extent depends on the copolymer concentration, copolymer nature and experimental procedure used. In fact, the amount of TAM solubilized significantly increases on increasing copolymer concentration. The drug is better solubilized by the PHEA–C16 copolymer and the solubilization capability decreases following the order PHEA–C16 > PHEA–PEG5000–C16 > PHEA–PEG2000–C16 > PHEA–PEG5000 > PHEA–PEG2000. The presence of the C16 moiety in the PHEA backbone leads to a solubilization ability which is roughly two times higher than that of copolymers bringing only the PEG chain. Moreover, the solubilization capability exerted by the copolymers is higher when the TAM is incorporated into the micelles during the micellization process with respect to that obtained when the drug is added to solutions containing pre-formed polymeric micelles. This trend suggests that the penetration of the drug molecules into the pre-formed micelles is hampered by the steric barrier constituted by the extended hydrophilic shell of the micelle. Further spectrophotometric results have evidenced that the drug loaded micelles are decidedly stable to dilution.