TY - JOUR
T1 - Mesoporous silica nanoparticles capped with chitosan-glucuronic acid conjugate for pH-responsive targeted delivery of 5-fluorouracil
AU - Narayan, Reema
AU - Gadag, Shivaprasad
AU - Mudakavi, Rajeev J.
AU - Garg, Sanjay
AU - Raichur, Ashok M.
AU - Nayak, Yogendra
AU - Kini, Suvarna G.
AU - Pai, Karkala Sreedhara Ranganath
AU - Nayak, Usha Y.
N1 - Funding Information:
The authors acknowledge the TEM facility, funded by a TPF Nanomission, GOI project at Centre for Nano and Soft Matter Sciences, Bengaluru.
Funding Information:
This project was partially funded by the Science and Engineering Research Board, India (Ref. No. EMR/2016/007006 ).
Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - In the present work, we designed mesoporous silica nanoparticles (MSNs) capped with chitosan-glucuronic acid (CHS-GCA) conjugate for pH-responsive targeted delivery of 5-fluorouracil (5-FU). The influence of the synthesis parameters on the shape and particle size of the MSNs was investigated. The size and morphology of the MSNs were found to be dependent on the amount of surfactant and inorganic silica source. 5-FU was encapsulated within the mesopores by utilizing three different techniques such as solvent immersion, impregnation and incipient wetness impregnation. A higher loading capacity of 172.5 ± 1.49 mg/g was obtained by the impregnation method. To ensure the controlled release of 5-FU, pH-sensitive chitosan was conjugated with glucuronic acid for enhanced uptake by lectin receptors. The developed 5-FU loaded MSNs coated with CHS-GCA showed a higher release of 82.46 ± 3.45% in pH 5.5 by the end of 72 h as compared to 63.84 ± 1.47% in pH 6.8, suggesting a pH-responsive release. Moreover, the CHS-GCA coated MSNs also showed a sustained release profile in colonic pH. Caecal contents further increased the release rate, which is evident from the higher rate constant. The IC50 of the developed formulations was found to be lower than that of pure 5-FU as observed from the cytotoxicity studies. Thus, we envision that the developed MSNs with a higher 5-FU payload might ensure targeted, controlled delivery of 5-FU to the tumor cells, thus reducing the dose and dose-associated toxicities.
AB - In the present work, we designed mesoporous silica nanoparticles (MSNs) capped with chitosan-glucuronic acid (CHS-GCA) conjugate for pH-responsive targeted delivery of 5-fluorouracil (5-FU). The influence of the synthesis parameters on the shape and particle size of the MSNs was investigated. The size and morphology of the MSNs were found to be dependent on the amount of surfactant and inorganic silica source. 5-FU was encapsulated within the mesopores by utilizing three different techniques such as solvent immersion, impregnation and incipient wetness impregnation. A higher loading capacity of 172.5 ± 1.49 mg/g was obtained by the impregnation method. To ensure the controlled release of 5-FU, pH-sensitive chitosan was conjugated with glucuronic acid for enhanced uptake by lectin receptors. The developed 5-FU loaded MSNs coated with CHS-GCA showed a higher release of 82.46 ± 3.45% in pH 5.5 by the end of 72 h as compared to 63.84 ± 1.47% in pH 6.8, suggesting a pH-responsive release. Moreover, the CHS-GCA coated MSNs also showed a sustained release profile in colonic pH. Caecal contents further increased the release rate, which is evident from the higher rate constant. The IC50 of the developed formulations was found to be lower than that of pure 5-FU as observed from the cytotoxicity studies. Thus, we envision that the developed MSNs with a higher 5-FU payload might ensure targeted, controlled delivery of 5-FU to the tumor cells, thus reducing the dose and dose-associated toxicities.
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U2 - 10.1016/j.jddst.2021.102472
DO - 10.1016/j.jddst.2021.102472
M3 - Article
AN - SCOPUS:85103137717
VL - 63
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
SN - 1773-2247
M1 - 102472
ER -