Functionalized injectable hydrogels for controlled insulin delivery.

The concept of this research is using poly(beta-amino ester) (PAE) as a duo-functional group for synthesis of the novel sensitive injectable hydrogel for controlled drug/protein delivery. Firstly, PAE made of 1,4-butanediol diacrylate and 4,4'-trimethylene dipiperidine is used as a pH-sensitive moiety to conjugate to the temperature-sensitive biodegradable triblock copolymer of poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) to manufacture pH/temperature-sensitive injectable hydrogel of pentablock copolymer PAE-PCL-PEG-PCL-PAE. Furthermore, the cationic nature of PAE is used as the second function to make the ionic complexes with anionic biomolecule loaded into the hydrogel such as insulin. As a result, the release of drug/protein from this hydrogel device can be controlled by the degradation of copolymer. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymer was investigated; the results showed that the aqueous media of the pentablock copolymer changed from a sol to a gel phase with increasing temperature and pH. The effect of anionic biomolecule such as insulin on sol-gel phase transition, degradation of the complex gel of the material with insulin was studied in vitro. Then the schematic of the ionic complexes between positive charges in PAE and the negatively charges in protein was simulated. In addition, the mechanism of controlled release behavior of insulin from the complex gel was supposed, which includes the chemically-controlled and diffusion-controlled stages. To prove the simulations, the cumulative release of the protein from the complex gel was investigated in vitro with different methods. Furthermore, the pharmacokinetic release of insulin from the complex gel in vivo on male Sprague-Dawley (SD) rats was compared with that from triblock copolymer hydrogel of PCL-PEG-PCL.

Sodium dodecyl sulfate-capillary gel electrophoresis of polyethylene glycolylated interferon alpha.

Sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE) using a hydrophilic replaceable polymer network matrix was applied to characterize the polyethylene glycol(PEG)ylated interferon alpha (PEG-IFN). The SDS-CGE method resulted in a clearer resolution in both the PEG-IFN species and the native IFN species. The distribution profile of PEGylation determined by SDS-CGE was consistent with that obtained by SDS-polyacrylamide gel electrophoresis (PAGE) with Coomassie blue or barium iodide staining. The result was also compared using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. SDS-CGE was also useful for monitoring the PEGylation reaction to optimize the reaction conditions, such as reaction molar ratio. This study shows the potential of SDS-CGE as a new method for characterizing the PEGylated proteins with advantages of speed, minimal sample consumption and high resolution.

Pharmacokinetic scaling of SJ-8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, by species-invariant time methods.

This study examined the pharmacokinetic disposition of SJ-8029, a novel anticancer agent possessing microtubule and topoisomerase inhibiting activities, in mice, rats, rabbits and dogs after i.v. administration. The serum concentration-time curves of SJ-8029 were best described by tri-exponential equations in all these animal species. The mean Cl, V(ss) and t(1/2) were 0.3 l/h, 0.1 l and 63.2 min in mice, 1.5 l/h, 1.6 l and 247.7 min in rats, 13.8 l/h, 39.6 l and 245.9 min in rabbits, and 29.2 l/h, 44.6 l and 117.4 min in dogs, respectively. Based on animal data, the pharmacokinetics of SJ-8029 were predicted in humans using simple allometry and also by several species-invariant time transformations using kallynochron, apolysichron and dienetichron times. The human pharmacokinetic parameters of Cl, V(ss) and t(1/2) predicted by the simple allometry and various species-invariant time methods were 50.4-145.0 l/h, 369.0-579.8 l and 242.0-1448.3 min, respectively. These preliminary parameter values may be useful in designing early pharmacokinetic studies of SJ-8029 in humans.