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PEGylated Single-Walled Carbon Nanotubes as Nanocarriers for Cyclosporin A Delivery

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Abstract

Single-walled carbon nanotubes (SWCNTs) have attracted the attention of many researchers due to their remarkable physicochemical features and have been found to be a new family of nanovectors for the delivery of therapeutic molecules. The ability of these nanostructures to load large amounts of drug molecules on their outer surface has been considered as the main advantage by many investigators. Here, we report the development of a PEGylated SWCNT-mediated delivery system for cyclosporin A (CsA) as a potent immunosuppressive agent. The available OH group in the CsA structure was first linked to a bi-functional linker (i.e., succinic anhydride) in order to provide a COOH terminal group. CsA succinylation process was optimized by using the modified simplex method. The resulting compound, CsA–CO–(CH2)2–COOH, was then grafted onto the exterior surface of SWCNTs, previously PEGylated with phospholipid–PEG5000–NH2 conjugates, through the formation of an amide bond with the free amine group of PEGylated SWCNTs. Drug loading, stability of the PEGylated SWCNT–CsA complex, and in vitro release of the drug were evaluated. Loading efficiencies of almost 72% and 68% were achieved by UV spectrophotometry and elemental analysis methods, respectively. It was observed that 57.3% of cyclosporine was released from CsA–Pl–PEG5000–SWCNTs after 3 days. In this investigation, we conjugated CsA to an amine-terminated phospholipid–polyethylene glycol chain attached on SWCNTs via a cleavable ester bond and demonstrated the possible potential of PEGylated SWCNT-based systems for CsA delivery.

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ACKNOWLEDGMENTS

The authors would like to thank Iran National Science Foundation (INSF) and Research Deputy of Shahid Beheshti University of Medical Sciences in Iran for the financial support of this research. This study is a part of the Ph.D. thesis of N. Hadidi, proposed and approved by the School of Pharmacy, Shahid Beheshti University of Medical Sciences (Iran).

Conflict of Interest

The authors report no conflicts of interest in this work.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Vali Asr Avenue, Niayesh Junction, Tehran, PO Box: 14155-6153, 1991953381, Iran

    Naghmeh Hadidi & Reza Aboofazeli

  2. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Farzad Kobarfard

  3. Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nastaran Nafissi-Varcheh

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  1. Naghmeh Hadidi
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  2. Farzad Kobarfard
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  4. Reza Aboofazeli
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Correspondence to Reza Aboofazeli.

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Hadidi, N., Kobarfard, F., Nafissi-Varcheh, N. et al. PEGylated Single-Walled Carbon Nanotubes as Nanocarriers for Cyclosporin A Delivery. AAPS PharmSciTech 14, 593–600 (2013). https://doi.org/10.1208/s12249-013-9944-2

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