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Sol-gel transition of PEG-PAF aqueous solution and its application for hGH sustained release

Sol-gel transition of PEG-PAF aqueous solution and its application for hGH sustained release
Shinde U.P.Joo M.K.Moon H.J.Jeong B.
Ewha Authors
Issue Date
Journal Title
Journal of Materials Chemistry
0959-9428JCR Link
vol. 22, no. 13, pp. 6072 - 6079
We report a poly(ethylene glycol)-poly(l-alanine-co-l-phenylalanine) (PEG-PAF) aqueous solution as a polypeptide-based thermogelling system and its application as an injectable sustained release system for human growth hormone (hGH). The PEG-PAF aqueous solution underwent sol-to-gel transition at 16-34 °C in a polymer concentration range of 6.0-14.0 wt% as the temperature increased. Dynamic light scattering, circular dichroism, FTIR, and 13C-NMR spectra indicated that the secondary structure of PAF was preserved, however, PEG was dehydrated in the sol-to-gel transition temperature range. A micelle aggregation model was suggested for the sol-to-gel transition of the current PEG-PAF, similar to previous polyesters. The polymer was quite stable in water, and therefore, the molecular weight of the polymer did not significantly change and pH of the aqueous polymer solution was maintained at 7.2-7.8 during the 1 month storage of the polymer as an aqueous solution at room temperature. This point is clearly distinguished from previous thermogelling polymers based on polyesters, polyorthoesters, polyphosphazenes, poly(β-aminoester urethane)s, and polyanhydrides, which generate acid degradation products or can be degraded during storage as an aqueous polymer solution. Therefore, the current system can be used as a ready-to-use injectable implant for biomedical applications. When the polymer aqueous solution (0.5 mL) was injected into the subcutaneous layer of rats, the gel was formed by temperature-sensitive sol-to-gel transition, and the gel was completely eliminated from the implanted site in <15 days. A haematoxylin and eosin (H&E) staining study suggests the good histocompatibility of the gel in the subcutaneous layer of rats. As a sustained release formulation for hGH, the PEG-PAF showed a 4 day release profile with a pharmacological effective concentration range of >1-5 ng mL -1in vivo, suggesting that the system is promising as a once-per-week delivery system for the hGH. This journal is © The Royal Society of Chemistry 2012.
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