Nanoparticulate tablet dosage form of lisofylline-linoleic acid conjugate for type 1 diabetes: in situ single-pass intestinal perfusion (SPIP) studies and pharmacokinetics in rat

As nano-sizing is becoming a more common approach for pharmaceutical product development, researchers are taking advantage of the unique inherent properties of nanoparticles for a wide variety of applications. This article reviews the physical and chemical stability of drug nanoparticles, including their mechanisms and corresponding characterization techniques. A few common strategies to overcome stability issues are also discussed. Published by Elsevier B.V.

The oral route is a preferred method of drug administration, though achieving effective drug delivery and minimizing off-target side effects is often challenging. Formulation into nanoparticles can improve drug stability in the harsh gastrointestinal (GI) tract environment, providing opportunities for targeting specific sites in the GI tract, increasing drug solubility and bioavailability, and providing sustained release in the GI tract. However, the unique and diverse physiology throughout the GI tract, including wide variation in pH, mucus that varies in thickness and structure, numerous cell types, and various physiological functions are both a barrier to effective delivery and an opportunity for nanoparticle design. Here, nanoparticle design aspects to improve delivery to particular sites in the GI tract are discussed. We then review new methods for evaluating oral nanoparticle formulations, including a short commentary on data interpretation and translation. Finally, the state-of-the-art in preclinical targeted nanoparticle design is reviewed.

Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.