Abstract
A potential sustained-release recombinant interleukin-2 (rIL-2) formulation was evaluated following intramuscular (i.m.) injection in rats. Poloxamer 407 (Pluronic® F-127) is a block copolymer comprised of polyoxyethylene and polyoxypropylene segments which exhibits the property of reverse thermal gelation. Thus, an rIL-2/poloxamer 407 preparation was injected i.m. in rats as a viscous mobile solution with subsequent gelation in vivo. Resultant plasma rIL-2 concentration-time data indicated absorption rate-limited disposition of rIL-2 following i.m. injection. The mean values of the absorption rate constant ( k clim were 0.64 ± 0.073 and 0.21 ± 0.019 h −1 following i.m. injection of an rIL-2 aqueous solution and the HL-2 gel formulation, respectively. The mean values of the elimination rate constant (k elim) were 1.76 ± 0.22 and 1.21 ±0.079 h −1 following administration of rIL-2 as an aqueous solution or gel formulation, respectively. The blood sampling time point at which the greatest plasma rIL-2 concentration (C max .) was observed was 2 h for rats injected i.m. with rIL-2 formulated in poloxamer 407 compared to 1 h for rats injected i.m. with an rIL-2 aqueous solution. The mean value of the C max. was significantly ( p < 0.05) less in rats injected i.m. with the rIL-2 gel formulation ( C max= 12500 ± 1450 pg/ml) compared to rats injected i.m. with an aqueous solution of rIL-2 ( C max = 19 600 ± 2650 pg/ml). The bioavailability of rIL-2 when injected i.m. as an rIL-2/poloxamer gel formulation relative to an i.m. injection of an rIL-2 aqueous solution was approx. 1.0. Cumulative amounts of rIL-2 recovered in the urine 48 h after an i.m. injection of either an rIL-2 aqueous solution or rIL-2 gel formulation were less than 1 percent of the administered dose. Since the rIL-2/poloxamer formulation evaluated in this study resulted in a decrease in the maximum blood concentration of rIL-2 achieved and an increase in the time required to reach a maximum blood concentration, without a reduction in the bioavailability of the protein, the rIL-2 gel formulation may represent an alternative, sustained-release mode of rIL-2 administration.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
