Drug Delivery and Translational Research - Featured Article: May 2024
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This study aimed to address the challenges associated with oral administration of therapeutic proteins, such as degradation and poor absorption. It proposed a novel approach combining mucus-permeating nanoparticles (NPs) with permeation enhancers for oral delivery of the monoclonal antibody bevacizumab. Bevacizumab forming a hydrophobic complex with sodium deoxycholate (DS), or sodium docusate (DOCU) was encapsulated in pegylated-coated albumin NPs. DOCU-loaded NPs showed reduced mucus diffusion compared to DS. In a C. elegans model, both DS and DOCU (free or nanoencapsulated) disrupted intestinal integrity without affecting overall survival. In rats, bevacizumab's relative oral bioavailability in polyethylene glycol-coated NPs complexed with DS was significantly increased (3.7 %), a 1000-fold improvement over free bevacizumab in NPs. DS effectiveness may be attributed to its ability to disrupt tight junctions, increase membrane fluidity, and inhibit certain enzymes. This strategy shows promise for enabling the therapeutic use of orally administered proteins, including monoclonal antibodies.
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