Review Nanoparticles as potential oral delivery systems of proteins and vaccines: A mechanistic approach Anne des Rieux a,b , Virginie Fievez a,b , Marie Garinot a , Yves-Jacques Schneider b , Véronique Préat a, ⁎ a Université catholique de Louvain, Unité de Pharmacie Galénique, Avenue E. Mounier, 73-20, 1200 Brussels, Belgium b Université catholique de Louvain, Institut des Sciences de la Vie, Laboratoire de Biochimie cellulaire, Croix du sud, 5, 1348 Louvain-La-Neuve, Belgium Received 21 April 2006; accepted 8 August 2006 Available online 23 August 2006 Abstract Peptides and proteins remain poorly bioavailable upon oral administration. One of the most promising strategies to improve their oral delivery relies on their association with colloidal carriers, e.g. polymeric nanoparticles, stable in gastrointestinal tract, protective for encapsulated substances and able to modulate physicochemical characteristics, drug release and biological behavior. The mechanisms of transport of these nanoparticles across intestinal mucosa are reviewed. In particular, the influence of size and surface properties on their non-specific uptake or their targeted uptake by enterocytes and/or M cells is discussed. Enhancement of their uptake by appropriate cells, i.e. M cells by (i) modeling surface properties to optimize access to and transport by M cells (ii) identifying surface markers specific to human M cell allowing targeting to M cells and nanoparticles transcytosis is illustrated. Encouraging results upon in vivo testing are reported but low bioavailability and lack of control on absorbed dose slow down products development. Vaccines are certainly the most promising applications for orally delivered nanoparticles. © 2006 Elsevier B.V. All rights reserved. Keywords: Nanoparticles; Oral delivery; M cells; Proteins; Vaccines; Biodegradable polymers Contents 1. Introduction ................................................................ 2 2. Nanoparticle formulation and physicochemical properties ........................................ 3 2.1. Different polymers developed to formulate nanoparticles ..................................... 3 2.2. Formulation principles ....................................................... 3 2.3. Formulation parameters influencing nanoparticle properties .................................... 4 2.4. Modification of nanoparticle surface to improve transport across the intestinal mucosa ..................... 4 2.4.1. Modification of nanoparticle surface properties ..................................... 5 2.4.2. Targeted nanoparticles .................................................. 5 3. Transport of nanoparticles across the intestinal mucosa ......................................... 5 3.1. Paracellular transport ....................................................... 6 3.2. Transcellular transport ....................................................... 6 3.2.1. Non-specific uptake of nanoparticles ........................................... 7 3.2.2. Uptake of targeted nanoparticles through the intestinal mucosa ............................ 11 4. Nanoparticles as potential oral delivery systems of peptides and vaccines ................................ 13 4.1. Oral delivery of therapeutic peptides and proteins ....................................... 13 Journal of Controlled Release 116 (2006) 1 – 27 www.elsevier.com/locate/jconrel ⁎ Corresponding author. Tel.: +32 2 764 73 20; fax: +32 2 764 73 98. E-mail address: preat@farg.ucl.ac.be (V. Préat). 0168-3659/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2006.08.013