Nanoparticles have received enormous attention as a promising tool to enhance target-specific drug delivery and diagnosis. Various in vitro and in vivo techniques are used to characterize a new system and predict its clinical efficacy. These techniques enable efficient comparison across nanoparticles and facilitate a product optimization process. On the other hand, we recognize their limitations as a prediction tool, which owe to inadequate applications and overly simplified test conditions. This article provides a critical review of in vitro and in vivo techniques currently used for evaluation of nanoparticles and introduces emerging techniques and models that may be used complementarily.

In vitro drug release kinetics studies are routinely performed to examine the ability of new drug formulations to modulate drug release. The underlying assumption is that the studies are performed in a sufficiently dilute solution, where the drug release is not limited by the solubility and the difference in release kinetics profile reflects the performance of a drug carrier in vivo. This condition is, however, difficult to meet with poorly water-soluble drug formulations, as it requires a very large volume of release medium relative to the formulation mass, which makes it challenging to measure the drug concentration accurately. These difficulties are aggravated with nanoparticle (NP) formulations, which are hard to separate from the release medium and thus require a dialysis bag or repeated high-speed centrifugation for sampling. Perhaps for these reasons, drug release kinetics studies of NPs of poorly water-soluble drugs are often performed in suboptimal conditions in which the NPs are not sufficiently diluted. However, such a practice can potentially underestimate drug release from NPs, leading to an inaccurate prediction that the NPs will attenuate the drug activity in vivo. Here we perform release kinetics studies of two different NP formulations of paclitaxel, a representative poorly water-soluble drug, according to common practices in the literature. We find that the drug release from NPs can be substantially underestimated depending on the choice of the release medium, NP/medium ratio, and handling of release samples. We discuss potential consequences of underestimating drug release, ending with suggestions for future studies with NP formulations of poorly water-soluble drugs.

Polymeric nanoparticles (NPs) are decorated with various types of molecules to control their functions and interactions with specific cells. We previously used polydopamine (pD) to prime-coat poly(lactic-co-glycolic acid) (PLGA) NPs and conjugated functional ligands onto the NPs via the pD coating. In this study, we report tannic acid (TA) as an alternative prime coating that is functionally comparable to pD but does not have drawbacks of pD such as optical properties and interference of ligand characterization. TA forms a stable and optically inert coating on PLGA NPs, which can accommodate albumin, chitosan, and folate-terminated polyethylene glycol to control the cell-NP interactions. Moreover, TA coating allows for surface loading of polycyclic planar aromatic compounds. TA is a promising reactive intermediate for surface functionalization of polymeric NPs.

For years, injectable polymeric nanoparticles (NPs) have been developed for delivering therapeutic agents to the tumors. Frequently, NPs surface have been modified with different moieties and/or ligands to impart stealth effect and/or elicit specific cellular interactions, both known to dramatically affect the in vivo fate and efficacy of these NPs. Areas covered: We discuss different types of ligands and molecules used for surface functionalization of polymeric NPs for tumor drug delivery. First, we summarize methods used through the literature for surface modification of polymeric NPs, then discuss challenges that face researchers either in decorating NPs with desired surface functionalities, characterizing functionalized surfaces or achieving intended cellular interactions and in vivo effects. Expert opinion: Modification of NP surfaces dramatically alters their behavior and favorably enhances their therapeutic efficacy. Choice of surface ligand/functionality should be based on intended therapeutic outcomes, taking into consideration the potential of clinical translation and scale up of the developed systems.