In vitro/in vivo correlation for 14C-methylated lysozyme release from poly(ether-ester) microspheres.
OBJECTIVE
The purpose of this study was to obtain an in vitro/in vivo correlation for the sustained release of a protein from poly(ethylene glycol) terephthalate (PEGT)/poly(butylene terephthalate) (PBT) microspheres.


METHODS
Radiolabeled lysozyme was encapsulated in PEGT/PBT microspheres via a water-in-oil-in-water emulsion. Three microsphere formulations varying in copolymer composition were administered subcutaneously to rats. The blood plasma was analyzed for radioactivity content representing released lysozyme at various time points post-dose. The in vitro release was studied in phosphate-buffered saline.


RESULTS
The encapsulation efficiency, calculated from the radioactivity in the outer water phase of the emulsion, varied from 60-87%. Depending on the PEG segment length and wt% PEGT, the lysozyme was released completely in vitro within 14 to 28 days without initial burst. 14C-methylated lysozyme could be detected in the plasma over the same time courses. The in vitro/in vivo correlation coefficients obtained from point-to-point analysis were greater than 0.96 for all microsphere formulations. In addition, less then 10% of administered radioactivity remained at dose site at 28 days for the microsphere formulations, indicating no notable retention of the protein at the injection site.


CONCLUSIONS
The in vitro release in phosphate-buffered saline and the in vivo release in rats showed an excellent congruence independent of the release rate of 14C-methylated lysozyme from PEGT/PBT microspheres.
van Dijkhuizen-Radersma
R
R
Chienna B.V., Prof. Bronkhorstlaan 10-D, 3723 MB Bilthoven, The Netherlands. riemke.van.dijkhuizen@chienna.com
Wright
S J
SJ
Taylor
L M
LM
John
B A
BA
de Groot
K
K
Bezemer
J M
JM
D000818:Animals; D004986:Ether; D004987:Ethers; D008863:Microspheres; D009113:Muramidase / Q000008:administration & dosage; D011091:Polyesters; D011108:Polymers
D004987:Ethers; D011091:Polyesters; D011108:Polymers; D004986:Ether; D009113:Muramidase