Nitric oxide (NO), a free radical gas molecule, functions as a potent antimicrobial agent in the innate immune system and plays an important role in the regulation of multiple physiological processes. For the first time in this work, a biocompatible platform based on halloysite nanotubes (HNTs) is developed for controlled delivery of NO. HNTs are natural aluminosilicate clay with a unique hollow tubular structure, good biocompatibility, high mechanical strength, and extensive functionality that make them ideal candidates as drug/therapeutics delivery systems. HNTs were first hydroxylated and modified with an aminosilane crosslinker, (3-aminopropyl) trimethoxysilane (APTMS), to enable the covalent attachment of a NO donor precursor, N-acetyl-d-penicillamine (NAP). HNT-NAP particles were then converted to NO-releasing S-nitroso-N-acetyl-penicillamine HNT-SNAP by nitrosation. A total of 0.10 ± 0.07 μmol/mg NO were loaded on HNTs which could be released at a tunable rate under different stimuli such as heat and light. The successful modification of HNTs was confirmed through different qualitative (Fourier-transform infrared spectroscopy and Nuclear magnetic resonance) and quantitative (Ninhydrin and Ellman) analyses. Transmission and scanning electron microscopies were also used to examine the morphology of the HNTs before and after modification. HNT-SNAP demonstrated concentration-dependent antibacterial effects against Gram-positive Staphylococcus aureus, with 99.6% bacteria reduction efficiency at a concentration of 10 mg/mL and showed no significant cytotoxicity toward 3T3 mouse fibroblast at concentrations equal or below 2 mg/mL. The SNAP-functionalized HNTs represent a novel and efficient NO delivery system with great flexibility to be incorporated into a variety of products, imparting NO release properties to a wide range of biomedical polymers without affecting the polymer’s backbone chemistry or crosslinking process and therefore can be used for several biomedical applications such as implants, catheters, tissue engineering scaffolds, wound dressings, and medical device coatings.

Sama Ghalei

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