Nano-Assemblies from Amphiphilic PnBA-b-POEGA Copolymers as Drug Nanocarriers.

Angeliki Chroni,Stergios Pispas,Thomas Mavromoustakos

doi:10.3390/polym13071164

Abstract

The focus of this study is the development of highly stable losartan potassium (LSR) polymeric nanocarriers. Two novel amphiphilic poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) copolymers with different molecular weight (Mw) of PnBA are synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization, followed by the encapsulation of LSR into both PnBA-b-POEGA micelles. Based on dynamic light scattering (DLS), the PnBA30-b-POEGA70 and PnBA27-b-POEGA73 (where the subscripts denote wt.% composition of the components) copolymers formed micelles of 10 nm and 24 nm in water. The LSR-loaded PnBA-b-POEGA nanocarriers presented increased size and greater mass nanostructures compared to empty micelles, implying the successful loading of LSR into the inner hydrophobic domains. A thorough NMR (nuclear magnetic resonance) characterization of the LSR-loaded PnBA-b-POEGA nanocarriers was conducted. Strong intermolecular interactions between the biphenyl ring and the butyl chain of LSR with the methylene signals of PnBA were evidenced by 2D-NOESY experiments. The highest hydrophobicity of the PnBA27-b-POEGA73 micelles contributed to an efficient encapsulation of LSR into the micelles exhibiting a greater value of %EE compared to PnBA30-b-POEGA70 + 50% LSR nanocarriers. Ultrasound release profiles of LSR signified that a great amount of the encapsulated LSR is strongly attached to both PnBA30-b-POEGA70 and PnBA27-b-POEGA73 micelles.

Highlights

Nano-drug delivery systems (NDDSs) have revolutionized drug delivery in the last few decades, endowing drugs with increased stability and water solubility, prolonging the cycle time, enhancing the uptake rate of target cells or tissues, reducing enzyme degradation, and controlling the release of the drug [1,2,3,4].The NDDSs used in modern biomedicine concern supramolecular self-assembled structures divided into organic, inorganic, and composite materials
Two amphiphilic PnBA30-b-POEGA70 and PnBA27-b-POEGA73 diblock copolymers were synthesized with different molecular weight (Mw) of a PnBA block
A representative size exclusion chromatography (SEC) chromatogram of 4000 g/mol PnBA and PnBA30-b-POEGA70 diblock is depicted in Figure 1, highlighting the increase in Mw after the addition of POEGA

Summary

Introduction

Nano-drug delivery systems (NDDSs) have revolutionized drug delivery in the last few decades, endowing drugs with increased stability and water solubility, prolonging the cycle time, enhancing the uptake rate of target cells or tissues, reducing enzyme degradation, and controlling the release of the drug [1,2,3,4]. The NDDSs used in modern biomedicine concern supramolecular self-assembled structures divided into organic, inorganic, and composite materials. The delivery of drugs, proteins, and nucleotides is possible via AmBCs self-assembled into biocompatible nanostructured multifunctional structures such as micelles, polymer containing liposomes, or polymeric nanoparticles [9]. The unique core-shell architecture of AmBC nanoassemblies enables a physical encapsulation of drug molecules into their hydrophobic micellar core, conferring an enhanced drug solubility and reduced toxicity. The hydrophilic shell stabilizes the core, ameliorates drug pharmacokinetics, and facilitates drug accumulation in tumors through the enhanced permeability and retention (EPR) effect [13,14]

Methods

Results

Conclusion