Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles
Background: Cisplatin is a widely-used potent anti-cancer drug having severe side-effects precluding its sustained use. Objectives: Poly (lactide-co-glycolide) (PLGA)-nanoparticles loaded Boldine, an antioxidant ingredient of ethanolic extract of Boldo plant (Peumus boldus) was tested in cancer mice...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Journal of Ayurveda and Integrative Medicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0975947617303352 |
| _version_ | 1818475291943632896 |
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| author | Jesmin Mondal Mousumi Patra Ashis Kumar Panigrahi Anisur Rahman Khuda-Bukhsh |
| author_facet | Jesmin Mondal Mousumi Patra Ashis Kumar Panigrahi Anisur Rahman Khuda-Bukhsh |
| author_sort | Jesmin Mondal |
| collection | DOAJ |
| description | Background: Cisplatin is a widely-used potent anti-cancer drug having severe side-effects precluding its sustained use. Objectives: Poly (lactide-co-glycolide) (PLGA)-nanoparticles loaded Boldine, an antioxidant ingredient of ethanolic extract of Boldo plant (Peumus boldus) was tested in cancer mice model, Mus musculus to examine if it could reduce unwanted Cisplatin-induced toxicity in normal tissue. Material and methods: Nano-encapsulation of Boldine was done by following the standardized solvent displacement method. Physico-chemical characterization of PLGA-encapsulated nano-Boldine (NBol) was accomplished through analyses of various spectroscopic techniques. Status of major antioxidant enzymes, functional markers, and lipid peroxidation (LPO) was also determined in certain tissue and serum samples. Percentage of cells undergoing cytotoxic death, Reactive oxygen species (ROS) accumulation and mitochondrial functioning were analyzed in both normal and cancer mice. Nanoscale changes in chromatin organization were assessed by Transmission electron microscopy (TEM). mRNA and protein expressions of Top II, Bax, Bcl-2, Cyt c, caspase 3 were studied by RT-PCR, immunoblot and immunofluorescence. Results: NBol had faster mobility, site-specific action and ability of sustained particle release. NBol readily entered cells, prevented Cisplatin to intercalate with dsDNA resulting in reduction of chromatin condensation, with corresponding changes in ROS levels, mitochondrial functioning and antioxidant enzyme activities, leading to reduction in Deoxyribose nucleic acid (DNA) damage and cytotoxic cell death. Expression pattern of apoptotic genes like Top II, p53, Bax, Bcl-2, cytochrome c and caspase-3 suggested greater cytoprotective potentials of NBol in normal tissues. Conclusions: Compared to Boldine (Bol), NBol had better ability of drug carriage and protective potentials (29.00% approximately) against Cisplatin-induced toxicity. Combinational therapeutic use of PLGA-NBol can reduce unwanted Cisplatin-induced cellular toxicity facilitating use of Cisplatin. Keywords: PLGA-nano-encapsulation, Boldine, Cisplatin, Multiorgan-toxicity, DNA-targeting, Signalling-pathway |
| first_indexed | 2024-12-10T09:11:02Z |
| format | Article |
| id | doaj.art-cec2041b23a342fa82655c1d39f7838b |
| institution | Directory Open Access Journal |
| issn | 0975-9476 |
| language | English |
| last_indexed | 2024-12-10T09:11:02Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ayurveda and Integrative Medicine |
| spelling | doaj.art-cec2041b23a342fa82655c1d39f7838b2022-12-22T01:55:01ZengElsevierJournal of Ayurveda and Integrative Medicine0975-94762020-01-011112436Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticlesJesmin Mondal0Mousumi Patra1Ashis Kumar Panigrahi2Anisur Rahman Khuda-Bukhsh3Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, IndiaMolecular Biology Laboratory, Department of Biochemistry and Biophysics, University of Kalyani, Kalyani 741235, IndiaFisheries and Aquaculture Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, IndiaCytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India; Corresponding author.Background: Cisplatin is a widely-used potent anti-cancer drug having severe side-effects precluding its sustained use. Objectives: Poly (lactide-co-glycolide) (PLGA)-nanoparticles loaded Boldine, an antioxidant ingredient of ethanolic extract of Boldo plant (Peumus boldus) was tested in cancer mice model, Mus musculus to examine if it could reduce unwanted Cisplatin-induced toxicity in normal tissue. Material and methods: Nano-encapsulation of Boldine was done by following the standardized solvent displacement method. Physico-chemical characterization of PLGA-encapsulated nano-Boldine (NBol) was accomplished through analyses of various spectroscopic techniques. Status of major antioxidant enzymes, functional markers, and lipid peroxidation (LPO) was also determined in certain tissue and serum samples. Percentage of cells undergoing cytotoxic death, Reactive oxygen species (ROS) accumulation and mitochondrial functioning were analyzed in both normal and cancer mice. Nanoscale changes in chromatin organization were assessed by Transmission electron microscopy (TEM). mRNA and protein expressions of Top II, Bax, Bcl-2, Cyt c, caspase 3 were studied by RT-PCR, immunoblot and immunofluorescence. Results: NBol had faster mobility, site-specific action and ability of sustained particle release. NBol readily entered cells, prevented Cisplatin to intercalate with dsDNA resulting in reduction of chromatin condensation, with corresponding changes in ROS levels, mitochondrial functioning and antioxidant enzyme activities, leading to reduction in Deoxyribose nucleic acid (DNA) damage and cytotoxic cell death. Expression pattern of apoptotic genes like Top II, p53, Bax, Bcl-2, cytochrome c and caspase-3 suggested greater cytoprotective potentials of NBol in normal tissues. Conclusions: Compared to Boldine (Bol), NBol had better ability of drug carriage and protective potentials (29.00% approximately) against Cisplatin-induced toxicity. Combinational therapeutic use of PLGA-NBol can reduce unwanted Cisplatin-induced cellular toxicity facilitating use of Cisplatin. Keywords: PLGA-nano-encapsulation, Boldine, Cisplatin, Multiorgan-toxicity, DNA-targeting, Signalling-pathwayhttp://www.sciencedirect.com/science/article/pii/S0975947617303352 |
| spellingShingle | Jesmin Mondal Mousumi Patra Ashis Kumar Panigrahi Anisur Rahman Khuda-Bukhsh Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles Journal of Ayurveda and Integrative Medicine |
| title | Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles |
| title_full | Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles |
| title_fullStr | Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles |
| title_full_unstemmed | Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles |
| title_short | Improved drug carriage and protective potential against Cisplatin-induced toxicity using Boldine-loaded PLGA nanoparticles |
| title_sort | improved drug carriage and protective potential against cisplatin induced toxicity using boldine loaded plga nanoparticles |
| url | http://www.sciencedirect.com/science/article/pii/S0975947617303352 |
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