Oral delivery and fate of poly(lactic acid) microsphere-encapsulated interferon in rats

In the light of previous findings which suggest that particulate material can be absorbed and thence systemically disseminated from the gastrointestinal tract, we have investigated the oral uptake and distribution of soluble and microsphere-encapsulated radiolabelled interferon-gamma. For trace-loaded (0.01% w/w interferon) microspheres, a quite different distribution of radioactivity was observed in-vivo 15 and 240 min after oral administration, in comparison with the control group which received equivalent doses of unencapsulated interferon-gamma. Thyroid gland activity in control animals killed at these times was significantly higher than that detected in those rodents receiving trace amounts 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-loaded particles released a significantly lower percentage of interferon-gamma in comparison with 0.97% w/w loaded microspheres (P less than or equal to 1). Bio-distribution data from rats treated orally with trace amounts of unencapsulated and microencapsulated interferon-gamma leads us to the tentative conclusion that microencapsulation of proteins markedly affects oral uptake, and possibly post-absorption pharmacokinetic parameters also.