Nanoparticle Drug Delivery: Focusing on The Therapeutic Cargo

Abstract

preferentially accumulate in areas of leaky vasculature through the enhanced permeability and retention (EPR) effect. This unique property allows NP therapeutics to target disease processes such as cancer and inflammatory diseases. NPs also possess other properties that are favorable for drug delivery. First, NPs are generally cleared by the monocyte phagocytic system and its cargo is cleared by hepatic clearance. This clearance mechanism is very different than that of most small molecules, which is via the kidneys. Hepatic clearance can be a favorable characteristic as it can potentially lower toxicity. Poor renal function is relatively common among the ill and the elderly. Druginduced nephrotoxicity has been a significant problem that has limited the use of many therapeutics [4]. For example, many cancer patients cannot receive cisplatin therapy owing to poor renal function. In comparison, most patients have normal hepatic function, and hepatotoxicity is much less common than nephrotoxicity [5]. Thus, NP delivery can potentially mitigate a therapeutic’s nephrotoxicity and increase its clinical use. Although recent publications have demonstrated the proof-of-principle of this approach in nanomedicine, it has not been fully explored [6]. Another property of NPs is their low distribution in normal organs, such as the heart and lungs. For therapeutics with cardiac or pulmonary toxicities as dose-limiting toxicities, NP delivery of these drugs can lower their toxicity profile. Indeed, the success of liposomal doxorubicin lies in its ability to limit drug distribution to the heart, which in turn lowers cardiac toxicity [7]. Using the same strategy, one can reduce the pulmonary toxicity of therapeutics, such as bleomycin, with NP formulations. The biodistribution of NPs can also lead to novel therapeutic applications. For Current efforts in nanoparticle drug delivery Nanoparticle (NP) drug delivery has garnered intense academic as well as commercial interest in recent years. Today, there are more than 20 clinically approved NP therapeutics with many more in clinical and preclinical development [1]. Most of the research efforts thus far have focused on the engineering and development of novel NP platforms. By contrast, there has been less attention devoted to studying the types of therapeutic cargo that NPs can deliver and their potential applications. Using the development of NP chemotherapeutics as an example, many of the preclinical and clinical investigations focused on the delivery of four drugs: doxorubicin, daunorubicin, paclitaxel and docetaxel. These drugs account for only two classes of chemotherapeutics, the anthracyclines and the taxanes [2]. Given that NP formulations of all four chemotherapeutics have been translated clinically, it is unlikely that additional research will result in the clinical development of new NP therapeutics containing these drugs. Another rationale to study NP delivery of these therapeutics is to compare a novel NP platform to an existing NP. However, a NP platform that is an excellent delivery vehicle for one drug may be a poor delivery vehicle for another. For example, liposomes are excellent for the delivery of hydrophilic anthracyclines, but efforts to use liposomes to deliver similarly hydrophilic platinum drugs have failed [3]. Therefore, there is a strong need to focus nanomedicine research on identifying potential therapeutics that will benefit from NP delivery.