Drug Release by Direct Jump from Poly(ethylene-glycol-b-ε-caprolactone) Nano-Vector to Cell Membrane.

Ugo Till,Laure Gibot,Christophe Mingotaud,Alix Poinso,Frédéric Violleau,Anne-Françoise Mingotaud,Jérôme Ehrhart,Jean-Pierre Souchard,Marie-Pierre Rols,Luc Wasungu,Patricia Vicendo

doi:10.3390/molecules21121643

Abstract

Drug delivery by nanovectors involves numerous processes, one of the most important being its release from the carrier. This point still remains unclear. The current work focuses on this point using poly(ethyleneglycol-b-ε-caprolactone) micelles containing either pheophorbide-a (Pheo-a) as a fluorescent probe and a phototoxic agent or fluorescent copolymers. This study showed that the cellular uptake and the phototoxicity of loaded Pheo-a are ten times higher than those of the free drug and revealed a very low cellular penetration of the fluorescence-labeled micelles. Neither loaded nor free Pheo-a displayed the same cellular localization as the labeled micelles. These results imply that the drug entered the cells without its carrier and probably without a disruption, as suggested by their stability in cell culture medium. These data allowed us to propose that Pheo-a directly migrates from the micelle to the cell without disruption of the vector. This mechanism will be discussed.

Highlights

Amphiphilic block copolymer micelles are nano-sized self-assembled particles with diameters between 10 and 100 nm [1,2]
The average diameter determined by Transmission Electron Microscopy (TEM) was smaller than the hydrodynamical diameter measured in solution
A few teams have examined the mechanisms of action involved in the drug release from copolymer micelles

Summary

Introduction

Amphiphilic block copolymer micelles are nano-sized self-assembled particles with diameters between 10 and 100 nm [1,2] These particles can increase the solubility of hydrophobic molecules due to their unique structural composition, which includes a hydrophobic core surrounded by a hydrophilic corona [3,4,5,6,7]. The hydrophilic corona ensures colloidal stability and biodispersity of the micelle These nanocarriers can be designed to escape opsonization and the mononuclear phagocytic system [9], which is one of the most important biological barriers to controlled drug delivery. This results in increased plasma half-life [10] and extended circulation time [11,12]. These nanocarriers can benefit from the enhanced permeability and retention effect, resulting in drug accumulation in cancerous tissues [13,14]

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