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Control of rhGH Release Profile from PEG-PAF Thermogel

Title
Control of rhGH Release Profile from PEG-PAF Thermogel
Authors
Shinde, Usha PramodMoon, Hyo JungKo, Du YoungJung, Bo KyongJeong, Byeongmoon
Ewha Authors
정병문
SCOPUS Author ID
정병문scopus
Issue Date
2015
Journal Title
BIOMACROMOLECULES
ISSN
1525-7797JCR Link1526-4602JCR Link
Citation
vol. 16, no. 5, pp. 1461 - 1469
Publisher
AMER CHEMICAL SOC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Poly(ethylene glycol)-poly(L-alanine-co-L-phenyl alanine) diblodk copolymers (PEG-PAF) of 2000-990 Da (P2K) and 50002530 Da (P5K) with the different molecular weights of PEGs, but having a similar molecular weight ratio of hydrophobic block to hydrophilic block were synthesized to compare their solution behavior and corresponding protein drug release profiles from their in situ formed thermogels. The PEG-PAF aqueous solutions underwent heat-induced sol-to-gel transition in a concentration range of 18.0-24.0 wt % and 8.0-12.0 wt % for P2K and P5K, respectively. 125K formed bigger micelles than P2K, of a broad distribution, whereas the PAP blocks of P5K developed richer in alpha-helix than those of P2K in the core of the micelles. As the temperature increased, the micelles underwent dehydration of the PEG, which led to the aggregation of micelles, while the secondary structure of PAP was slightly affected during the sol-to-gel transition. The P5K exhibited higher tendency to aggregate and formed a tighter gel than P2K. Upon injection into the subcutaneous layer of rats, both polymer aqueous solutions formed a biocompatible gel with typical mild inflammatory tissue responses. Recombinant human growth hormone (rhGH) maintained its stability without forming any aggregates in both sol (4 degrees C) and gel (37 degrees C) states of the PEG-PAFs. Even though P2K and P5K have a similar molecular weight ratio of hydrophobic block to hydrophilic block, the P5K system exhibited a reduced initial burst release, improved bioavailability, and prolonged therapeutic duration of the rhGH, compared to the P2K system. The current research suggests that a drug release profile is a complex function of self-assembling carriers and incorporated drugs, and thus, a promising protein delivery system could be designed by adjusting the molecular parameters of a thermogel.
DOI
10.1021/acs.biomac.5b00325
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자연과학대학 > 화학·나노과학전공 > Journal papers
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