Cargo–carrier interactions significantly contribute to micellar conformation and biodistribution

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.

Advances in PEG-based ABC terpolymers and their applications

“…Cargo-carrier interactions signicantly contributed to the properties of encapsulated drugs and their localization within the micelles. 91…”

Deterioration of Organ Function As a Hallmark in Sepsis: The Cellular Perspective

“…Whereas inhibition of PI3Kγ could be a strategy to counter liver failure, the same signaling molecule might confer protection in other organs, e.g., in the heart ( 20 ). This highlights the need to achieve organ and cell-specific targeting of these processes in multi-organ dysfunction ( 21 , 22 ).…”

“…Hence, before signaling mediators can be used therapeutically, it will be necessary to overcome the significant hurdles posed by these multifunctional signaling molecules. Nanoparticle-based targeted drug-delivery ( 21 , 22 , 59 ) might help to specifically tackle this problem.…”

Analysis of Dissolution of Salicylamide from Carrageenan Based Hard-Shell Capsules: A Study of the Drug-Matrix Interaction

“…Unfortunately, there is minimum information discussing the effect of interaction between a drug and its matrix to its release profile, specifically for the matrix in the form of a hard-shell capsule. Press et al [2] reported that polyether-based triblock tricopolymer micelles act as an agent to give the effect to the physicochemical properties of the matrix as well as the actual conditions during encapsulation interfere during the formulation of nanoparticular drug-matrix systems. On the other hand, drug molecules may directly interact with matrix molecules, lowering their solubility and/or retarding their release from the matrixes [1,3].…”