title: Orally active-targeted drug delivery systems for proteins and peptides.
abstract: BACKGROUND
  In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption.
  
  
  METHODS
  This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed.
  
  
  CONCLUSIONS
  ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai, 201203 , China +86 21 20231000 1424 ; +86 21 20231000 1425 ; simm2122@vip.sina.com.
authors: Xiuying
authors: X
authors: Li
authors: Miaorong
authors: M
authors: Yu
authors: Weiwei
authors: W
authors: Fan
authors: Yong
authors: Y
authors: Gan
authors: Lars
authors: L
authors: Hovgaard
authors: Mingshi
authors: M
authors: Yang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010539:Permeability; D011485:Protein Binding; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D008024:Ligands; D010455:Peptides; D011506:Proteins
keywords: IgG-Fc receptor; active-targeted drug delivery systems; intercellular adhesion molecule-1; oral protein and peptide delivery; proton-coupled folate transporter; recombinant fusion protein; transferrin receptor