Encapsulation in biodegradable microparticles enhances serum antibody response to parenterally-delivered β-amyloid in mice
摘要
Poly(lactide-co-glycolide) (PLG) microspheres were tested as a parenteral delivery system for human β-amyloid (1–42) (Aβ), a potential immunotherapeutic undergoing assessment in Phase 1 studies for Alzheimer's disease (AD). Aβ was successfully encapsulated in PLG microspheres of average sizes of 3 or 15 μm diameter. Swiss Webster (SW) mice were injected by the sub-cutaneous (s.c.) or intra-peritoneal (i.p.) routes with 3–33 μg Aβ. Aβ-PLG microparticles (3 μm) induced dose-dependent antibody responses, which were maximal at 33 μg Aβ, while Aβ 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 Aβ-specific antibodies cleared amyloid plaques in a mouse model of AD (Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid β-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.