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

被引:15
作者
KHAN, MZI
TUCKER, IG
OPDEBEECK, JP
机构
[1] UNIV QUEENSLAND,DEPT PHARM,BRISBANE,QLD 4072,AUSTRALIA
[2] UNIV QUEENSLAND,DEPT PARASITOL,BRISBANE,QLD 4072,AUSTRALIA
[3] UNIV OTAGO,SCH PHARM,DUNEDIN,NEW ZEALAND
基金
澳大利亚研究理事会;
关键词
BIODEGRADABLE LIPID IMPLANT; SUSTAINED RELEASE; ANTIGEN DELIVERY; PEPTIDE DELIVERY; ANTIBODY RESPONSE; CHOLESTEROL; LECITHIN; SINGLE-SHOT IMMUNIZATION;
D O I
10.1016/0378-5173(93)90198-O
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 implanting 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 administration. An initial burst release of BSA was observed within 2 days of implantation followed by a trickle delivery over 7 months. During the first 5 days, the rate of release of BSA from C pellets (without PC) was 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 content of the pellets. The implants containing BSA induced anti-BSA antibodies at 2 months and maintained the same levels of antibodies for up to 10 months. BSA delivered in the form of three injections produced the same level of antibodies as C-PC pellets of 1:2 ratio (w/w), but a significantly 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 rate.
引用
收藏
页码:255 / 262
页数:8
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