Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats
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 biodeg...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Saudi Pharmaceutical Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016419301598 |
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| author | Prem Kumar Govindappa Darukeshwara Joladarashi Raghavendra Lakshmana Shetty Hallur Jagadeesh S. Sanganal Ayyalasomayajula Ratna Phani |
| author_facet | Prem Kumar Govindappa Darukeshwara Joladarashi Raghavendra Lakshmana Shetty Hallur Jagadeesh S. Sanganal Ayyalasomayajula Ratna Phani |
| author_sort | Prem Kumar Govindappa |
| collection | DOAJ |
| description | 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. Keywords: 6-Mercaptopurine, Chitosan, Nanoparticle, Anti-cancer, Toxicity |
| first_indexed | 2024-04-13T10:08:43Z |
| format | Article |
| id | doaj.art-8e8413622e7d42b6a45edd1821d15d43 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-04-13T10:08:43Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-8e8413622e7d42b6a45edd1821d15d432022-12-22T02:51:01ZengElsevierSaudi Pharmaceutical Journal1319-01642020-01-01281147154Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in ratsPrem Kumar Govindappa0Darukeshwara Joladarashi1Raghavendra Lakshmana Shetty Hallur2Jagadeesh S. Sanganal3Ayyalasomayajula Ratna Phani4Department of Orthopaedics and Rehabilitation, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA; Department of Veterinary Pharmacology and Toxicology, Veterinary College, Hebbal, Bangalore, Karnataka 560 024, India; Corresponding author at: Department of Orthopaedics and Rehabilitation, The Pennsylvania State University College of Medicine, 500 University Drive, Mail Code H089, Hershey, PA 17033, USA.Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USADepartment of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), CEP18618-687 São Paulo, BrazilDepartment of Veterinary Pharmacology and Toxicology, Veterinary College, Hebbal, Bangalore, Karnataka 560 024, IndiaInnovative Nano and Micro Technologies Private Limited, Mysore Road, Bangalore, Karnataka 5600059, IndiaBackground: 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. Keywords: 6-Mercaptopurine, Chitosan, Nanoparticle, Anti-cancer, Toxicityhttp://www.sciencedirect.com/science/article/pii/S1319016419301598 |
| spellingShingle | Prem Kumar Govindappa Darukeshwara Joladarashi Raghavendra Lakshmana Shetty Hallur Jagadeesh S. Sanganal Ayyalasomayajula Ratna Phani Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats Saudi Pharmaceutical Journal |
| title | Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
| title_full | Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
| title_fullStr | Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
| title_full_unstemmed | Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
| title_short | Toxicity evaluation of 6-mercaptopurine-Chitosan nanoparticles in rats |
| title_sort | toxicity evaluation of 6 mercaptopurine chitosan nanoparticles in rats |
| url | http://www.sciencedirect.com/science/article/pii/S1319016419301598 |
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