In vitro and in vivo release of albumin using a biodegradable MPEG-PCL diblock copolymer as an in situ gel-forming carrier.
An MPEG-PCL diblock copolymer was synthesized as an in situ gel carrier, and its phase transition behavior in aqueous solutions was examined. For comparison, aqueous solutions of Pluronic F-127, a widely used injectable gel-forming solution, were also studied. Both MPEG-PCL copolymer and Pluronic aqueous solutions were sols at room temperature. As the temperature was increased above room temperature, the diblock copolymer and Pluronic solutions underwent a sol-to-gel phase transition, which manifested as an increase in viscosity indicative of the formation of a gel. All of the copolymer solutions became gels at body temperature, although the gel viscosity increased with the increasing concentration of the MPEG-PCL diblock copolymer in the solution. In in vitro experiments, in which the gels were exposed to PBS, the MPEG-PCL gels maintained their structural integrity for more than 28 days, whereas the Pluronic gel disappeared within 2 days. The same results were observed when the polymer solutions were subcutaneously injected into rats. The MPEG-PCL gels maintained their structural integrity longer than 30 days, while the Pluronic gel could not be observed after 2 days. The ability of the gels as drug carriers was studied by measuring the release of fluorescein isothiocyanate-labeled bovine serum albumin (BSA-FITC) from MPEG-PCL diblock copolymer gels in vitro as well as in vivo. In vitro, BSA release was sustained above 20 days, with a greater release at lower diblock copolymer concentration; by contrast, Pluronic gels exhibited almost complete release of BSA-FITC within 1 day. When the BSA-FITC-loaded diblock copolymer and Pluronic solutions were subcutaneously injected into rats, they immediately transformed into a gel. In vivo, sustained release of BSA-FITC over 30 days was observed from the MPEG-PCL gel, whereas BSA-FITC release from the Pluronic gel ceased within 3 days. Collectively, the present findings show that MPEG-PCL diblock copolymer solutions are thermo-responsive and maintain their structural integrity under physiological conditions, indicating that they are suitable for use as injectable drug carriers.
Hyun
Hoon
H
Medicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejeon 305-600, Korea.
Kim
Yu Han
YH
Song
In Bum
IB
Lee
Jung Won
JW
Kim
Moon Suk
MS
Khang
Gilson
G
Park
Kinam
K
Lee
Hai Bang
HB
D000418:Albumins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005782:Gels / Q000737:chemistry; D007279:Injections, Subcutaneous; D044367:Phase Transition; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011091:Polyesters / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014783:Viscosity; D014867:Water / Q000737:chemistry
D000418:Albumins; D004337:Drug Carriers; D005782:Gels; D011091:Polyesters; D012996:Solutions; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D014867:Water; D020442:Poloxamer; D011092:Polyethylene Glycols