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Title: Investigations on scale up and shelf-stability of curcumin encapsulated polymer nanoparticles for treating inflammatory and vascular diseases
Author: Grama, Charitra Nagesh
ISNI:       0000 0004 2746 4905
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2013
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Curcumin, a natural spice of Indian origin is the active principle present in the yellow spice turmeric. However, this molecule is under-utilized due to its poor peroral bioavailability. Very recently, we have demonstrated that encapsulation of curcumin in biodegradable nanoparticles improve oral bioavailability of curcumin. This study reports scale-up and shelf-stability of curcumin encapsulated poly (lactic acid-coglycolic acid) (PLGA) nanoparticles (nCUR). The nCUR were prepared by emulsification solvent evaporation/diffusion method and by varying the process parameters such as homogenisation duration we could successfully prepare large quantities nCUR. The particle size decreased as the homogenisation duration increased from 5 min to 30 min and the particles were spherical. The particle characteristics of large scale preparation (particle size 288.7 ± 3.4 nm and curcumin entrapment efficiency of 52.5 ± 4.3%) were similar to those obtained by lab-scale preparation. The freeze dried nCUR were subjected to six-month ICH shelf-stability conditions suitable for room temperature and refrigerated storage. The nCUR were found to retain the stability over test period as determined by particle characteristics and curcumin integrity using AFM, zeta sizer and XRD analysis. Curcumin has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Therefore, attempts were made to evaluate the potential of nCUR in models of diabetic cataract, stroke and cancer. In diabetic cataract model, oral administration of 2 mg/day nCUR was significantly more effective than curcumin in delaying cataract progression independent of its glucose lowering ability but with significant effect on aldose reductase pathway reducing sorbitol levels and osmotic pressure. The nCUR was found to be very effective in acute ischemic stroke and the activity was mediated via prevention of oxidative stress, inflammation and MMPs over expression. However, nCUR was not as effective as reported in the literature in ovarian cancer xenograft, but a slight reduction towards 18-19 days post implantion but was not significant. On the other hand, nCUR was ineffective in B16 F0 orthotopic xenograft lung tumour model. Together, this data indicate the potential of curcumin in treating a variety of diseases and nCUR was superior due to its ability to improve peroral bioavailability.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available