Facile Method to Prepare pH-Sensitive PEI-Functionalized Carbon Nanotubes as Rationally Designed Vehicles for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Delivery

Vassilis Tangoulis,Nikolia Lalioti,George Psomas,Eugenia Valsami-Jones,Nathan Langford,Vlasoula Bekiari,Chrisoula Kakoulidou,John Parthenios

doi:10.3390/c6040062

Abstract

A new pH-sensitive system designed for drug-delivery purposes and based on functionalized multiwall magnetic carbon nanotubes (Mag-CNTs) was synthesized for the effective incorporation of non-steroidal anti-inflammatory drugs (NSAIDs), aiming at drug release in characteristic acidic conditions close to the actual conditions of inflamed tissues. Cationic hyperbranched polyethyleneimine (PEI) was immobilized on the surface of Mag-CNTs via electrostatic interactions between the positively charged protonated amines within the polymer and the carboxyl groups on the chemically oxidized Mag-CNT surface. The addition of the NSAID with a carboxylate donor, Naproxen (NAP), was achieved by indirect coupling through the amino groups of the intermediate linker PEI. FT-IR, Raman, and UV–vis spectroscopy were employed to fully characterize the synthesized nanocarrier and its functionalization procedure. The interaction of the designed nanocarrier with bovine serum albumin (BSA) was studied in vitro by fluorescence emission spectroscopy while its in vitro interaction with calf-thymus (CT) DNA was monitored by UV–vis spectroscopy and viscosity measurements and via competitive studies with ethidium bromide. The calculated binding constants were compared to those of free NAP revealing a higher binding affinity for BSA and CT DNA. Finally, drug-release studies were performed, revealing that the electrostatic linkage ensures an effective release of the drug in the acidic pH typical of inflamed cells, while maintaining the multiwall nanotubes (MWNTs)–drug conjugates stable at the typical bloodstream.

Highlights

A fascinating category of nanomaterials possessing unique physical, chemical, and physiological properties is carbon nanotubes (CNTs) [1,2,3,4,5,6]
Samples were filtered by employing a vacuum filter funnel of pore size number 3, and either hydrophobic polytetrafluoroethylene (PTFE) membrane filters (0.45 μm pore size) or cellulose nitrate membrane filters (0.45 μm pore size). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, (EDC, >98.0%, Triethylamine (Et3N, ≥99.5%) and N- hydroxysuccinimide (NHS, 98.0%), trisodium citrate, NaCl, calf-thymus (CT) DNA, bovine serum albumin (BSA) and ethidium bromide (EB)
Mag-CNTs could be functionalized with groups containing oxygen, such as –OH and –COOH, mainly at the outer sidewall ends where several defects are introduced during the oxidation procedure

Summary

Introduction

A fascinating category of nanomaterials possessing unique physical, chemical, and physiological properties is carbon nanotubes (CNTs) [1,2,3,4,5,6] Their chemical modification has attracted increasing attention over recent years in order to improve their solubility and compatibility, tailor their structures and properties, and open a whole new world of novel CNT-based nanostructures and. As a matter of fact, CNTs possess many intriguing features that make them attractive drug-delivery carriers such as: (a) An enhanced permeability and retention (EPR) effect. As a matter of fact, CNTs possess are a direct consequence of the existence of magnetic interactions, possible crystal structure disorders many intriguing features that make them attractive drug-delivery carriers such as: a) An enhanced and intrinsic negative spin polarization [55,56]

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Conclusion