OctoDex(TM) is one of OctoPlus' proprietary microsphere delivery systems for the controlled release of therapeutic proteins. The delivery system is based on hydrogel microspheres, consisting of degradable networks of crosslinked dextrans. In the latest issue of Pharmaceutical Research, OctoPlus reveals information about in vitro-in vivo correlations (IVIVC) of hGH-loaded OctoDex(TM) microspheres in Pit-1 deficient Snell dwarf mice and in healthy human volunteers.

Various batches of microspheres were aseptically produced at two different scales. Briefly, aqueous solutions of hydroxyethyl methacrylate derivatized dextran (dex-HEMA) with a degree of HEMA substitution of 16, poly(ethylene glycol) (PEG) and the protein were emulsified and allowed to polymerize to form microspheres.

IVIVC calculations were performed using a one-compartment linear model, where it is assumed that the absorption and the elimination of hGH follow first order kinetics. The authors ultimately compared the calculated hGH serum concentration time data to the measured hGH serum concentration time data.

In mice, the pharmacodynamic effect (i.e. an increase in body lenght of the mice) was found to correlate well with the in vitro release curves. Serum hGH concentration in male volunteers after s.c. administration of hGH-loaded dex-HEMA microspheres was also in good agreement with the calculated serum concentrations using the mentioned pharmacokinetic model.

Source: Vlugt-Wensink KDF, de Vrueh R, Gresnigt MG, Hoogerbrugge CM, van Buul-Offers SC, de Leede LGJ, Sterkman LGW, Crommelin DJA, Hennink WE, Verrijk R. Pharmaceutical Research 24(12) (2007) 2239-2248