Vijay Kumar1, Ankita Leekha1, Aakriti Tyagi1, Ankur Kaul2, Anil Kumar Mishra2, Anita Kamra Verma3. 1. Nano Biotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India. 2. Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, 110054, India. 3. Nano Biotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India. akamra23@hotmail.com.
Abstract
PURPOSE: The study purposes to evaluate nanocrystalline biopolymeric nanoparticles encapsulating methotrexate and dexamethasone with high biocompatibility, enhanced therapeutic efficacy and reduced toxicity. METHODS: Chitosan nanoparticles were prepared by ionic gelation, and Methotrexate (MTX) and Dexamethasone (DEX) were loaded during the preparation and screened for their in vitro efficacy in HEK and RAW264.7 cells, ex vivo and in vivo efficacy. RESULTS: FTIR confirmed the involvement of phosphoric group of sTPP with amine groups of chitosan and also role of hydrogen bonding involved in the preparation of MTXCHNP and DEXCHNP. Controlled release patterns coupled with diffusion of drug were observed in two different buffers (PBS) at pH 7.4 and pH 5.8. The IC50 for MTXCHNP for HEK was 26.1 μg/ml and 7.7 μg/ml for RAW 264.7 cells. In DEXCHNP, the IC50 was 20.12 μg/ml for HEK and 7.37 μg/ml for RAW264.7 cells. Enhanced uptake of FITC-CHNP by RAW cells indicated internalization of nanoparticles by phagocytosis. The enhanced release of drug at lower pH justified increased cytotoxicity. Negligible ex-vivo hemolysis indicated the higher biocompatibility of the nanoparticles. 99mTc-CHNP exhibited maximum absorption in blood circulation in 3 h, followed by hepatic metabolism and renal clearance. Higher in-vivo anti-arthritic activity and antioxidant activity was observed post-intraperitoneal (i.p.) injections by both MTXCHNP and DEXCHNP when compared to MTX (0.75 mg/Kg by i.p. route) and DEX (0.2 mg/Kg/i.p./daily) per se. CONCLUSION: The nanocrystalline biopolymeric nanoparticles were stable, biocompatible and have potential to be administered through i.p. route with minimal toxicity and high efficacy.
PURPOSE: The study purposes to evaluate nanocrystalline biopolymeric nanoparticles encapsulating methotrexate and dexamethasone with high biocompatibility, enhanced therapeutic efficacy and reduced toxicity. METHODS: Chitosan nanoparticles were prepared by ionic gelation, and Methotrexate (MTX) and Dexamethasone (DEX) were loaded during the preparation and screened for their in vitro efficacy in HEK and RAW264.7 cells, ex vivo and in vivo efficacy. RESULTS: FTIR confirmed the involvement of phosphoric group of sTPP with amine groups of chitosan and also role of hydrogen bonding involved in the preparation of MTXCHNP and DEXCHNP. Controlled release patterns coupled with diffusion of drug were observed in two different buffers (PBS) at pH 7.4 and pH 5.8. The IC50 for MTXCHNP for HEK was 26.1 μg/ml and 7.7 μg/ml for RAW 264.7 cells. In DEXCHNP, the IC50 was 20.12 μg/ml for HEK and 7.37 μg/ml for RAW264.7 cells. Enhanced uptake of FITC-CHNP by RAW cells indicated internalization of nanoparticles by phagocytosis. The enhanced release of drug at lower pH justified increased cytotoxicity. Negligible ex-vivo hemolysis indicated the higher biocompatibility of the nanoparticles. 99mTc-CHNP exhibited maximum absorption in blood circulation in 3 h, followed by hepatic metabolism and renal clearance. Higher in-vivo anti-arthritic activity and antioxidant activity was observed post-intraperitoneal (i.p.) injections by both MTXCHNP and DEXCHNP when compared to MTX (0.75 mg/Kg by i.p. route) and DEX (0.2 mg/Kg/i.p./daily) per se. CONCLUSION: The nanocrystalline biopolymeric nanoparticles were stable, biocompatible and have potential to be administered through i.p. route with minimal toxicity and high efficacy.
Authors: Pradip Kumar; Ramavtar Meena; R Paulraj; A Chanchal; A K Verma; H B Bohidar Journal: Colloids Surf B Biointerfaces Date: 2011-10-25 Impact factor: 5.268
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