Orally administered liposomal formulations for colon targeted drug delivery

Colon targeted drug delivery is an active area of research for diseases affecting the colon, as it shows promise in improving the efficacy of therapeutics and reducing systemic toxicity. Improved oral drug delivery design has unequivocally improved the bioavailability of drugs to the colon. The oral route of administration is the most common method of drug delivery. It is the preferred route of administration because of increased patient convenience and reduced invasiveness. Rectal formulations may seem ideal for colon targeted drug delivery; however in addition to the issues surrounding patient administration, the efficacy of these formulations is limited to conditions affecting the distal colon and rectum. They are not effective for the treatment of more widespread inflammation of the colon, which occurs in conditions such as Inflammatory Bowel Disease (IBD). Oral formulations can be designed to achieve either a local or systemic delivery of therapeutics. Local treatment requires that the drug will be delivered to the site of action within the gastrointestinal (GI) tract to have a localized effect, but will not be absorbed or only poorly absorbed. Systemic delivery for orally administered drugs requires systemic absorption occurring within the intestines prior to distribution of drug around the body. For conditions involving localized inflammation to the tissues of the colon, the ideal formulation would be one that (i) is administered orally, (ii) is able to reach the colon, (iii) delivers high concentrations of drug at the site of inflammation, and (iv) is not systemically absorbed. Current formulations have limited effect on specificity of targeting to diseased colon tissue vs. healthy colon tissue. In addition, despite coverage to the surface of the colon (including diseased tissue), there is no guarantee that the drug is effectively taken up into the tissue and cells at the site of inflammation. Therefore, the use of nanotechnology in formulation design has been investigated as a way to further improve the efficacy of therapeutics by allowing specific targeting and uptake into inflamed tissue within the colon (Jani et al., 1989, 1990). Nanoformulations have been developed for the targeted treatment of a number of pathological conditions, including IBD, cancers, and infections (Vingerhoeds et al., 1994; Singh, 1999; Maruyama, 2002). For the purpose of GI tract targeting, liposomes can be manipulated by the inclusion of polymer coatings on the liposomal surface. These coatings allow oral liposomal formulations to resist degradation in the hostile environment of the GI tract, which include bile salts and enzymes (e.g., pancreatic lipases) that would normally dissolve the lipid bilayer (Iwanaga et al., 1999; Takeuchi et al., 2003; Karn et al., 2011). This article will briefly discuss strategies which have been investigated for targeting drug-encapsulated liposomes to the colon.