The protein delivery properties of polymer supramolecular assemblies were investigated by using recombinant human growth hormone (rh-GH) and two polyhydroxyethylaspartamide (PHEA) derivatives: (a) PHEA-C16 obtained by PHEA random grafting with hexadecylalkylamine; (b) PHEA-PEG 5000-C16 obtained by PHEA random co-grafting with hexadecylalkylamine and 5 kDa poly(ethylene glycol). The two polymers possessed similar self-assembling properties: critical micelle concentration (CMC) and particle size. The protein loading (protein/polymer, w/w, %) was 12.1+/-1.3% and 8.5+/-0.4% with PHEA-C16 and PHEA-PEG 5000-C16, respectively. The rh-GH/polymer association constant calculated by Scatchard analysis was 1.87 x 10(5)M(-1) with PHEA-C(16) and 0.27 x 10(5)M(-1) with PHEA-PEG 5000-C16. The Klotz analysis showed that 5 PHEA-C16 and 9 PHEA-PEG 5000-C16 polymer chains associated with one protein molecule. The protein dissociation from the PHEA-C16 and PHEA-PEG 5000-C16 supramolecular complexes was complete in about 350-450 and 450-550 h, respectively. With both polymers, the protein release was faster as the protein/polymer ratio increased. Pharmacokinetic studies were performed by subcutaneous administration to rats of protein/polymer solutions at different w/w ratios (1:75 and 1:150). Both polymer formulations slowed the protein absorption. The protein bioavailability increased as the protein/polymer complex stability decreased and the protein/polymer w/w ratio increased indicating that efficient protein delivery can be achieved by proper polymer choice and formulation composition.