Chapter 4 - Biopharmaceutical challenges in using lipid nanoparticles for oral chemotherapy

Abstract

Oral chemotherapy has the potential to create “hospitalization-free chemotherapy,” a dream shared by oncologists, formulation scientists, and patients. Such a therapeutic approach will improve patient’s compliance, alleviate patient caregivers’ distress, and significantly reduce treatment costs. Under current clinical practice, intravenous injection or infusion chemotherapy leads to undesired side-effects, such as plasma concentrations beyond maximum safe concentration, rapid body clearing, and decreased bioavailability. Low-aqueous solubility and drug stability, and the presence of biological barriers (e.g., multidrug efflux transporter in the gastrointestinal tract) may be overcome when using nanoparticles for oral administration of chemotherapeutic drugs. Lipid nanoparticles (LNPs), such as solid LNPs, nanostructured lipid carriers, nano-lipid–drug conjugates, mixed micelles, liposomes, and nano-emulsions have shown some promising results for oral drug delivery. Besides acting as absorption enhancers, LNPs also improve the oral drug bioavailability due to their ability to inhibit first-pass metabolism through chylomicron-linked and/or M-cell absorption. LNPs decrease administered drug inter- and intrasubject pharmacokinetic variation. In addition, some classes of phospholipids and surfactants used in LNP formulations inhibit P-glycoprotein efflux. In this chapter we address the biopharmaceutical challenges in oral cancer chemotherapy and how LNPs can overcome these challenges. The effect of a GI tract environment on LNPs as well as some pharmacokinetics are also discussed.