Poly-hydroxyethylaspartamide supramolucular system for prolonged rh-GH delivery.

Purpose: Two PHEA self-assembling derivatives were developed for parenteral administration of rh-GH. Results: PHEA-C16 and PHEA-PEG5-C16 yielded 12.1±1.3% and 8.5±0.4% protein/polymer (w/w) loading, respectively. The Scatchard and Klotz analysis showed that rh-GH associates more tightly and is released more slowly from PHEA-C16 as compared to PHEA-PEG5-C16. In vivo, the polymer association prolonged the drug absorption (tmax) and increased the bioavailability (AUC) as compared to the free protein. The protein bioavailability obtained with PHEA-PEG5-C16 was higher than that obtained with PHEA-C16 and increased as the protein/polymer ratio increased. Conclusions: amphiphilic PHEAs can be successfully exploited to yield sustained protein delivery. Modulation of the polymer composition and protein/polymer ratio allows the optimisation of the protein association and release kinetic to yield effective protein delivery.