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Chitosan-Folate Coated Mesoporous Silica Nanoparticles As a Smart and Ph-Sensitive System for Curcumin Delivery Publisher



Daryasari MP1 ; Akhgar MR1 ; Mamashli F2 ; Bigdeli B2 ; Khoobi M3, 4
Authors
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Authors Affiliations
  1. 1. Department of Chemistry, Kerman Branch, Islamic Azad University, Kerman, Iran
  2. 2. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
  3. 3. Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutical Biomaterials, Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: RSC Advances Published:2016


Abstract

In this work, normal and large pore size mesoporous silica nanoparticles (NMSNs and LMSNs) were prepared by co-condensation method and coated with (3-aminopropyl)triethoxysilane (APTES) to prepare amine functionalized MSNs (MSN-NH2). They were then conjugated with succinic anhydride (SA) to obtain carboxylic acid functionalized MSNs (MSN-COOH). Curcumin (CUR) as a hydrophobic drug was loaded into the synthesized MSNs with two different pore sizes to compare the loading capacity and efficiency. The results showed that LMSNs had 2-fold larger loading efficiency and capacity for CUR than NMSNs. Chitosan (CS), as a pH-sensitive polymer, was also conjugated to folic acid (FA) as an active targeting agent and then coated on the surface of carboxylic acid enriched MSNs via electrostatic interaction. The MSNs were fully characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential analysis, dynamic light scattering (DLS), nitrogen adsorption/desorption analysis, thermo gravimetric analysis (TGA), XRD analysis, NMR and UV-visible spectroscopies. The mechanism of CUR release from CS-FA coated LMSNs was pH-sensitive and in vitro release modeling revealed that CUR is released via Korsmeyer-Peppas mechanism. No significant toxicity was observed for CUR free MSNs, while the CUR loaded MSNs inhibited proliferation of HeLa and NIH-3T3 cell lines, showing more cytotoxic effect on cancerous HeLa cells. Moreover, the selective cellular uptake of CUR loaded LMSNs-COOH@CS-FA by folate receptor-positive HeLa cells was assessed and confirmed. Hemocompatibility and protein corona of the target carrier were also studied to show negligible hemolytic activity and suitable protein-target LMSNs interactions. © The Royal Society of Chemistry.