Multifunctional Dendrimers for Drug Nanocarriers

Introduction

In the recent years, significant progress has been achieved in the field of nanotechnology, especially in drug delivery (Shi, Votruba, Farokhzad, & Langer, 2010; Elsabahy & Wooley, 2012; Markman, Rekechenetskiy, Holler, & Ljubimova, 2013). Some traditional drugs have to face the drawbacks, such as poor aqueous solubility, undesired side-effects and low bioavailability (Allen & Cullis, 2013; Patel, Zhou, Piepmeier, & Saltzman, 2012), which dramatically decrease their applications in clinic. With the quick development of nanotechnology, numerous nanocarriers have been employed to solve these problems, because of their outstanding performance with targeting, delayed release, high solubility and dispensability. Most widely used nanocarriers based on polymers such as nanoparticles, micelles and liposomes are efficient, while they are metastable in vivo for the self-assembled nanocarriers and it is difficult to precisely control the size, structure and the surface properties of the nanocarriers (Markman et al., 2013; Torchilin, 2014). Furthermore, conventional polymers are typically polydisperse in molecular weight, resulting in poorly controlled the physicochemical properties of nanocarriers, which inevitably cause serious issues in pharmacokinetic study in clinical trials.

Contrast to the conventional polymers, dendrimers are nanosized, monodisperse, highly branched polymers with well-defined topological structure which have attracted much attention for drug delivery applications (Astruc, Boisselier, & Ornelas, 2010; Mintzer & Grinstaff, 2011). Most of them can improve the aqueous solubility and bioavailability of drugs by physically encapsulating in the voids or covalently attaching to the surface groups (D'Emanuele & Attwood, 2005). Dendrimers also have other advantages in drug delivery, such as stable structure, passive tumor targeting by enhanced penetration and retention (EPR) effect, large number of peripheral functional groups, monodisperse size, reproducible synthesis and hydrophobic interiors for drug encapsulation (Cheng, Zhao, Li, & Xu, 2011; Lee, MacKay, Fréchet, & Szoka, 2005; Medina & El-Sayed, 2009). In addition, the dendrimers are feasible modified by functional groups such as active targeting moieties, drugs, imaging agents and stimuli-sensitive elements (Cheng et al., 2011; Singh, Gupta, Asthana, & Jain, 2008). More importantly, the use of dendrimers as drug carriers has reproducible pharmacokinetics which plays a vital role for the drug delivery system in clinical application (Cheng et al., 2011).