Sreekanth Reddy Obireddy1,2, Wing-Fu Lai2. 1. Department of Chemistry, Sri Krishnadevaraya University, Anantapur, 515003, India. 2. Ciechanover Institute of Precision and Regenerative Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen, 518172, People's Republic of China.
Abstract
PURPOSE: Magnetic nanoparticles have been used in diverse pharmaceutical applications because they can potentially be used to target specific sites. In the present work, a new type of nanocomposites is designed as a carrier of controlled bioactive agent delivery. METHODS: Amine-functionalized magnetic nanoparticles (amine-MNPs) are coupled with carboxymethyl chitosan (CMC) to generate the nanocomposites, namely MNPs-CMC, which can be further loaded with doxorubicin (DOX) to produce MNPs-CMC-DOX. The generated nanocomposites are characterized by using various techniques (including FTIR, 1H-NMR, DSC, TGA, SEM, TEM and XRD). In vitro drug release studies are conducted in PBS with different pH values (1.2 and 6.8) at different temperatures (25°C and 37°C). The toxicity of the nanocomposites is tested in MCF-7 and 3T3 cells. The ROS-generating capacity of the nanocomposites is determined in treated cells using 2',7'-dichlorodihydrofluorescein diacetate. RESULTS: The structures of MNPs, CMC, and nanocomposites are confirmed by FTIR, XRD, and 1H-NMR data reveals the formation of CMC from chitosan (CS). The size of MNPs is estimated by TEM to be around 25 nm. After conjugation with CMC, the size of the nanocomposites increases to 46-57 nm. Based on the release profiles of MNPs-CMC-DOX, our nanocomposites are pH-responsive. In addition, our nanocomposites show reactive oxygen species (ROS)-generating capacity and cell type-dependent toxicity. CONCLUSION: Our nanocomposites show high potential for use in bioactive agent delivery. Along with their ROS-generating capacity, they warrant further development as pH-responsive carriers for therapeutic applications.
PURPOSE: Magnetic nanoparticles have been used in diverse pharmaceutical applications because they can potentially be used to target specific sites. In the present work, a new type of nanocomposites is designed as a carrier of controlled bioactive agent delivery. METHODS: Amine-functionalized magnetic nanoparticles (amine-MNPs) are coupled with carboxymethyl chitosan (CMC) to generate the nanocomposites, namely MNPs-CMC, which can be further loaded with doxorubicin (DOX) to produce MNPs-CMC-DOX. The generated nanocomposites are characterized by using various techniques (including FTIR, 1H-NMR, DSC, TGA, SEM, TEM and XRD). In vitro drug release studies are conducted in PBS with different pH values (1.2 and 6.8) at different temperatures (25°C and 37°C). The toxicity of the nanocomposites is tested in MCF-7 and 3T3 cells. The ROS-generating capacity of the nanocomposites is determined in treated cells using 2',7'-dichlorodihydrofluorescein diacetate. RESULTS: The structures of MNPs, CMC, and nanocomposites are confirmed by FTIR, XRD, and 1H-NMR data reveals the formation of CMC from chitosan (CS). The size of MNPs is estimated by TEM to be around 25 nm. After conjugation with CMC, the size of the nanocomposites increases to 46-57 nm. Based on the release profiles of MNPs-CMC-DOX, our nanocomposites are pH-responsive. In addition, our nanocomposites show reactive oxygen species (ROS)-generating capacity and cell type-dependent toxicity. CONCLUSION: Our nanocomposites show high potential for use in bioactive agent delivery. Along with their ROS-generating capacity, they warrant further development as pH-responsive carriers for therapeutic applications.
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