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

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.

pH-Sensitive Gold Nanorods for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Delivery and DNA-Binding Studies

“…Given the molecular mass of NAP (230.2 g/mol), the corresponding constants could be expressed in mg/mL and are much higher than those of AuNRs@PEG@NAP. In addition, the constant of AuNRs@PEG@NAP could be considered comparable with those of a previously reported carbon nanotube and spin-crossover nanoparticle loaded with naproxen [43,44].…”

“…This may suggest that the incorporation of naproxen in the AuNRs@PEG may lead to a tighter interaction with CT DNA than the free NAP. A comparison of the DNA-binding constant of AuNRs@PEG@NAP with the reported metal-naproxen complexes may reveal that AuNRs@PEG@NAP is a slightly tighter DNA-binder than the Co(II) [37], Cu(II) [38], and most Mn(II) [35,36] complexes of naproxen, and similar to Sn(IV) [41] and Ag(I) [42] complexes, while the polyethyleneimine-functionalized carbon nanotube hosting naproxen [43], the water-soluble silica hybrid spin-crossover nanoparticle loaded with naproxen [44], and the reported Ni(II)-naproxen complexes present higher K b values [39] than AuNRs@PEG@NAP.…”

Cytotoxicity of Carbon Nanotubes, Graphene, Fullerenes, and Dots

“…Raman spectroscopy investigations of carbon nanomaterials for cytotoxic studies were performed in Refs. [43,75]. Figure 1e shows the Raman spectra of the NL001 sample that belongs to the sample pristine sample, the NL002 samples that are the pristine material functionalized by -COOH groups, and the NL004 sample that is functionalized by polyethyleneimine@Naproxen.…”

“…Figure 8a shows the drug release from the PEI-functionalized carbon nanotubes at different pH [43]. It is visible that the release of drugs is maximal at pH 4.1.…”

“…The toxicology issues are connected with drug delivery and bioimaging. The drug delivery is controlled by water solubility, biocompatibility, blood circulation time, targeting, and accumulation of therapeutics in diseased cells and tissues for carbon nanotubes [39][40][41][42][43][44][45][46][47][48][49], graphene [50][51][52][53][54][55][56][57][58][59][60][61][62], fullerenes [63], dots [64][65][66][67]. The diagnostic method, bioimaging, is connected with the penetration of drugs and diagnostic agents into tissues and cells and the sensitivity of detection.…”