title: Poloxamer-based in situ hydrogels for controlled delivery of hydrophilic macromolecules after intramuscular injection in rats.
abstract: 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 °C-31.7 °C, might be freely chosen to achieve comparable pharmacokinetics for hydrophilic macromolecular drugs after intramuscular injection.
authors.affiliation: College of Chinese Materia Medica and.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: XiaoLi
authors.initials: X
authors.lastname: Shi
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.forename: ChunXia
authors.initials: C
authors.lastname: Yao
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Feng
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry* / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D007273:Injections, Intramuscular; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008970:Molecular Weight; D044367:Phase Transition; D020442:Poloxamer / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D046911:Macromolecular Substances; D020442:Poloxamer
keywords: In situ gel; intramuscular injection; macromolecular drug; poloxamer; sustained-release