EVALUATION OF CHOLESTEROL-LECITHIN IMPLANTS FOR SUSTAINED DELIVERY OFANTIGEN - RELEASE INVIVO AND SINGLE-STEP IMMUNIZATION OF MICE

Bovine serum albumin (BSA), a model antigen, was delivered from matrix systems (pellets) prepared from cholesterol (C) alone, and from C and hydrogenated egg lecithin (PC) in various C-PC ratios, to mice by imp lanting the pellets subcutaneously. The in vivo release profile of BSA from these pellets and the antibody responses to BSA were studied at intervals over a period of 10 months following a single-dose administr ation. An initial burst release of BSA was observed within 2 days of i mplantation followed by a trickle delivery over 7 months. During the f irst 5 days, the rate of release of BSA from C pellets (without PC) wa s significantly slower than from C-PC pellets of 4:1 and 8:1 ratios (w /w). At day 9, the differences became insignificant. The concentration of BSA retained in the pellets increased with an increase in PC conte nt of the pellets. The implants containing BSA induced anti-BSA antibo dies at 2 months and maintained the same levels of antibodies for up t o 10 months. BSA delivered in the form of three injections produced th e same level of antibodies as C-PC pellets of 1:2 ratio (w/w), but a s ignificantly lower level than that produced by the C pellets and C-PC pellets of 1:1, 2:1, 4: 1 and 8:1 ratios (w/w) (P < 0.04). Bioerosion of the C-PC pellets (at less-than-or-equal-to 4:1, w/w) was noticeable and an increase in PC content of the pellets increased the erosion ra te.