Autor(es): Govindappa, Prem Kumar ; Joladarashi, Darukeshwara ; Hallur, Raghavendra Lakshmana Shetty [UNESP] ; Sanganal, Jagadeesh S. ; Phani, Ayyalasomayajula Ratna
Data: 2020
Identificador Persistente: http://hdl.handle.net/11449/199875
Origem: Oasisbr
Assunto(s): 6-Mercaptopurine; Anti-cancer; Chitosan; Nanoparticle; Toxicity; 6-Mercaptopurine; 6-Mercaptopurine; Anti-cancer; Anti-cancer; Chitosan; Chitosan; Nanoparticle; Nanoparticle; Toxicity; Toxicity
Made available in DSpace on 2020-12-12T01:51:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01
H2020 LEIT Nanotechnologies
Background: The 6-mercaptopurine (6-MP) is an effective immunosuppressant and anti-cancer drug. However, the usage of 6-MP is limited due to its well-known side effects, such as myelotoxicity and hepato-renal toxicity. To curtail the potential toxic effects, we have used chitosan as a natural biodegradable and biocompatible polysaccharide to synthesize 6-Mercaptopurine-Chitosan Nanoparticles (6-MP-CNPs). Methods: The 6-MP-CNPssize, morphology, physicochemical interactions, and thermal stability were characterized using Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC), respectively. The loading efficiency of the 6-MP in CNPs was estimated using LCMS/MS. Then, the 6-MP-CNPs were subjected to in vivo acute and sub-acute oral toxicity evaluations. Results: The DLS and SEM analysis respectively indicated size (70.0 nm to 400.0 nm), polydispersity index (0.462), and zeta potential (54.9 mV) with improved morphology of 6-MP-CNPs. The FTIR and DSC results showed the efficient interactive and stable nature of the 6-MP-CNPs, which sustained the drug-delivery process. The loading efficiency of 6-MP-CNPs was found to be 25.23%. The chitosan improved the lethal dose (LD50 cut off) of 6-MP-CNPs (1000 mg/kg b.w) against 6-MP (500 mg/kg b.w) and also significantly (p ≤ 0.05) reduces the toxic adverse effect (28-day repeated oral dose) on hemato-biochemical and hepato-renal histological profiles. Conclusion: The findings suggest that chitosan, as a prime drug-delivery carrier, significantly alleviates the acute and sub-acute toxic effects of 6-MP.
Department of Orthopaedics and Rehabilitation College of Medicine The Pennsylvania State University
Department of Veterinary Pharmacology and Toxicology Veterinary College, Hebbal
Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida
Department of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP)
Innovative Nano and Micro Technologies Private Limited, Mysore Road
Department of Gynecology and Obstetrics Botucatu Medical School (FMB) São Paulo State University (UNESP)
