Clemencia Pinilla

Targeting approaches to oral drug delivery

Delivery of pharmaceuticals, particularly biotechnology products such as proteins, peptides, genes, oligonucleotides and vaccines, via the oral route remains problematic to this day. Instability in the gastrointestinal environment and poor permeability across the intestinal epithelial cell barrier contribute to poor oral bioavailability for many of these compounds. Current targeting strategies to overcome these issues are focused on three-part systems in which the drug (i) is loaded into a protective particulate carrier (ii) which is coated with target-specific ligands (iii) which mediate site-specific delivery of the drug-carrier complex. Protection from gastrointestinal degradative processes combined with site-specific delivery to absorptive regions of the intestinal tract is purported to yield high local concentrations of the drug of choice in close proximity with the epithelial cell layer and hence, transport across that barrier through a variety of mechanisms. This review examines the impact of cutting-edge technologies such as genomics and combinatorial chemistry on targeted oral drug delivery strategies. The explosion in rate of identification of new targets using genomics, together with high-throughput screening for target-specific ligands using combinatorial chemistry and phage display, has the potential to revolutionise this field. Particular reference is made to advances associated with targeted delivery of vaccines to M-cells or antigen-presenting cells in gut-associated lymphoid tissues.

Successful identification of novel agents to control infectious diseases from screening mixture‐based peptide combinatorial libraries in complex cell‐based bioassays

Mixture‐based peptide synthetic combinatorial libraries (SCLs) represent a valuable source for the development of novel agents to control infectious diseases. Indeed, a number of studies have now proven the ability of identifying active peptides from libraries composed of thousands to millions of peptides in cell‐based biosystems of varying complexity. Furthermore, progressing knowledge on the importance of endogenous peptides in various immune responses lead to a regain in importance for peptides as potential therapeutic agents. This article is aimed at providing recent studies in our laboratory for the development of antimicrobial or antiviral peptides derived from mixture‐based SCLs using cell‐based assays, as well as a short review of the importance of such peptides in the control of infectious diseases. Furthermore, the use of positional scanning (PS) SCL‐based biometrical analyses for the identification of native optimal epitopes specific to HIV‐1 proteins is also presented.