Drug Delivery System Based on pH-Sensitive Biocompatible Poly(2-vinyl pyridine)-b-poly(ethylene oxide) Nanomicelles Loaded with Curcumin and 5-Fluorouracil.

Camelia-Elena Iurciuc-Tincu,Marcel Popa,Lacramioara Ochiuz,Monica Stamate Cretan,Violeta Purcar,Leonard Ionut Atanase,Oana Maria Daraba

doi:10.3390/polym12071450

Abstract

Smart polymeric micelles (PMs) are of practical interest as nanocarriers for the encapsulation and controlled release of hydrophobic drugs. Two hydrophobic drugs, naturally-based curcumin (Cur) and synthetic 5-fluorouracil (5-FU), were loaded into the PMs formed by a well-defined pH-sensitive poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP90-b-PEO398) block copolymer. The influence of the drug loading on the micellar sizes was investigated by dynamic light scattering (DLS) and it appears that the size of the PMs increases from around 60 to 100 nm when Cur is loaded. On the contrary, the loading of the 5-FU has a smaller effect on the micellar sizes. This difference can be attributed to higher molar mass of Cur with respect to 5-FU but also to higher loading efficiency of Cur, 6.4%, compared to that of 5-FU, 5.8%. In vitro drug release was studied at pH 2, 6.8, and 7.4, and it was observed that the pH controls the release of both drugs. At pH 2, where the P2VP sequences from the “frozen-in” micellar core are protonated, the drug release efficiencies exceed 90%. Moreover, it was demonstrated, by in vitro assays, that these PMs are hemocompatible and biocompatible. Furthermore, the PMs protect the Cur against the photo-degradation, whereas the non-ionic PEO corona limits the adsorption of bovine serum albumin (BSA) protein on the surface. This study demonstrates that these pH-sensitive PMs are suitable for practical utilization as human-safe and smart, injectable drug delivery systems.

Highlights

The emergence of nanotechnology has had a profound impact on clinical therapeutics in the last two decades
It was of interest to investigate the behavior of this micellar system, as a smart drug delivery system, as it was concluded that the micellization process is pH-dependent and starts at pH values higher than 4.5, which is the pKa of the P2VP sequence [24]
By dynamic light scattering (DLS), it was demonstrated that the micellar sizes of the drug-loaded systems are higher than that of the drug-free polymeric micelles (PMs) and that this increase is correlated with the molar mass of the loaded drugs

Summary

Introduction

The emergence of nanotechnology has had a profound impact on clinical therapeutics in the last two decades. PMs are obtained by the self-assembly of individual polymer chains (unimers) of amphiphilic block or graft copolymers when they are directly dissolved in an aqueous or non-aqueous solution (dissolution method) above a critical micelle concentration (C.M.C) or a critical micelle temperature (C.M.T) [2,5,6,7]. In addition to this basic method, other micellization techniques are described in the literature: film hydration, precipitation, and dialysis methods starting from a common solvent. Micelles can be economically produced on a large scale, which is an important practical advantage [9]

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Conclusion