Encapsulation in biodegradable microparticles enhances serum antibody response to parenterally-delivered β-amyloid in mice

Poly(lactide-co-glycolide) (PLG) microspheres were tested as a parenteral delivery system for human R-amyloid (1-42) (A beta), a potential immunotherapeutic undergoing assessment in Phase 1 studies for Alzheimer's disease (AD). A beta was successfully encapsulated in PLG microspheres of average sizes of 3 or 15 mum diameter. Swiss Webster (SW) mice were injected by the sub-cutaneous (s.c.) or intra-peritoneal (i.p.) routes with 3-33 mug A beta. A beta -PLG microparticles (3 mum) induced dose-dependent antibody responses, which were maximal at 33 Vg A beta, while A beta in phosphate-buffered saline (PBS) produced weak antibody responses at the same doses by both routes. Significantly increased antibody responses were seen for both small and large particle formulations given by the i.p. route in comparison to the s.c route. It was previously reported that passive immunisation with A beta -specific antibodies cleared amyloid plaques in a mouse model of AD (Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta -peptide enter the nervous system and reduce pathology in a mouse model of Alzheimer disease. Nature Med 2000;6:916-19), an indication that induction of serum antibody is a prerequisite for efficacy. (C) 2001 Elsevier Science Ltd. All rights reserved.