期刊
DRUG DELIVERY
卷 22, 期 3, 页码 375-382出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10717544.2014.891272
关键词
In situ gel; intramuscular injection; macromolecular drug; poloxamer; sustained-release
资金
- Program for New Century Excellent Talents in University [NCET-13-0906]
- National Natural Science Foundation of China [81073065]
- Key Discipline Project of Shanghai Education Committee [J50302]
- 085'' Project [085ZY1219]
- Xinglin Scholar Program of Shanghai University of TCM
This study is aimed to investigate the applicability of poloxamer 407 (P407) and 188 (P188)-based temperature-sensitive in situ hydrogel (TSHG) in sustained delivery of hydrophilic macromolecules following intramuscular administration. Polyethylene glycols (PEGs) with molecular weight of 5-, 20-, and 40-kDa were used as model drugs, which can represent the common size range of hydrophilic macromolecular drugs using TSHG. The correlation between the level of poloxamers and thermogelling transition temperatures (Tsol-gel) was established and two formulations 20% P407/10% P188'' and 24% P407/10% P188'' were chosen for further study. The results showed that the release kinetics of PEGs was close to zero order. Sustained in vivo behaviors were achieved by both of the two formulations for all the PEGs though variations were seen. Lower molecular weight PEG showed more remarkable pharmacokinetic improvements. No significant differences in pharmacokinetics were observed between the two formulations for the same PEG. This suggested that 20-24% P407/10% P188 formulations, with accordingly Tsol-gel in the range of 24.6 degrees C-31.7 degrees C, might be freely chosen to achieve comparable pharmacokinetics for hydrophilic macromolecular drugs after intramuscular injection.
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