ORAL DELIVERY AND FATE OF POLY(LACTIC ACID) MICROSPHERE-ENCAPSULATED INTERFERON IN RATS

In the light of previous findings which suggest that particulate mater ial can be absorbed and thence systemically disseminated from the gast rointestinal tract, we have investigated the oral uptake and distribut ion of soluble and microsphere-encapsulated radiolabelled interferon-g amma. For trace-loaded (0.01% w/w interferon) microspheres, a quite di fferent distribution of radioactivity was observed in-vivo 15 and 240 min after oral administration, in comparison with the control group wh ich received equivalent doses of unencapsulated interferon-gamma. Thyr oid gland activity in control animals killed at these times was signif icantly higher than that detected in those rodents receiving trace amo unts of microencapsulated interferon-gamma (P less than or equal to 0. 05). For poly(L-lactide) particles with higher interferon loadings (0. 97% w/w interferon-gamma) the distinction between the two experimental groups was less significant. During incubation in-vitro, the trace-lo aded particles released a significantly lower percentage of interferon -gamma in comparison with 0.97% w/w loaded microspheres (P less than o r equal to 1). Bio-distribution data from rats treated orally with tra ce amounts of unencapsulated and microencapsulated interferon-gamma le ads us to the tentative conclusion that microencapsulation of proteins markedly affects oral uptake, and possibly post-absorption pharmacoki netic parameters also.