Abstract
Strategies to deliver drugs using nanocarriers, which are passively or actively targeted to their alleged site of action might favorably affect benefit–risk profiles of novel therapeutics. Here we tested the hypothesis whether the physico-chemical properties of the cargo as well as the actual conditions during encapsulation interfere during formulation of nanoparticular cargo–carrier systems. On the basis of previous work, a versatile class of nanocarriers is polyether-based ABC triblock terpolymer micelles with diameters below 50 nm. Their tunable chemistry and size allows to systematically vary important parameters. We demonstrate in vivo differences in pharmacokinetics and biodistribution not only dependent on micellar net charge but also on the properties of encapsulated (model) drugs and their localization within the micelles. On the basis of in vitro and in vivo evidence we propose that depending on drug cargo and encapsulation conditions micelles with homogeneous or heterogeneous corona structure are formed, contributing to an altered pharmacokinetic profile as differences in cargo location occur. Thus, these interactions have to be considered when a carrier system is selected to achieve optimal delivery to a given tissue.
Highlights
Strategies to target drugs passively or actively to specific cells or tissues may allow interference with central signaling events in health and disease
Polymer-based nanocarriers are the largest class of non-viral vectors. Their pharmacology and toxicology were shown to depend on size, composition, surface charge and shape; these key factors seemingly determine nanoparticle uptake, immune cell recognition and circulation time.[3,4,5,6,7]
The micelles (ECT and ENT) were prepared according to literature[21] as follows: in total, 50 mg of the corresponding triblock terpolymer was dissolved in 2.5 ml of THF, and 2.0 mg of Nile red (NR) or V19 was added to the solution
Summary
Strategies to target drugs passively or actively to specific cells or tissues may allow interference with central signaling events in health and disease. A broad spectrum of approaches, including viruses and non-viral vectors has been applied for delivery to specific cells, but these strategies are still far from satisfactory. Polymer-based nanocarriers are the largest class of non-viral vectors. Their pharmacology and toxicology were shown to depend on size, composition, surface charge (zeta potential) and shape; these key factors seemingly determine nanoparticle uptake, immune cell recognition and circulation time.[3,4,5,6,7] Often carriers with cationic net charge interact strongly with and are capable of penetrating the cellular membrane, leading to high delivery efficiencies but this is often accompanied by impaired cell viability and clearance by the reticuloendothelial system.[8,9]
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