Chitosan-Alginate Microcapsules Provide Gastric Protection and Intestinal Release of ICAM-1-Targeting Nanocarriers, Enabling GI Targeting In Vivo.

When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve oral delivery of NCs to treat gastrointestinal (GI) pathologies or for systemic absoption. However, GI instability of targeting moieties compromises this strategy. We explored whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NCs release and targeting in intestinal conditions. We used nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or non-specific IgG. NCs (~160-nm) were encapsulated in ~180-μm microcapsules with an alginate core, in the absence or presence of a chitosan shell. We found >95% NC encapsulation within microcapsules and <10% NC release from microcapsules in storage. There was minimal NC release at gastric pH (<10%) and burst release at intestinal pH (75-85%), slightly attenuated by chitosan. Encapsulated NCs afforded increased protection against degradation (3-4 fold) and increased cell targeting (8-20 fold) after release vs. non-encapsulated NCs. Mouse oral gavage showed that microencapsulation provided 38-65% greater protection of anti-ICAM NCs in the GI tract, 40% lower gastric retention, and 4-9-fold enhanced intestinal biodistribution vs. non-encapsulated NCs. Therefore, microencapsulation of antibody-targeted NCs may enable active targeting strategies to be effective in the context of oral drug delivery.