Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.757475
Title: Curcumin containing chitosan-pectinate nanoparticulate drug delivery system for colon cancer treatment
Author: Alkhader, Enas Ali
ISNI:       0000 0004 7430 2925
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2018
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Abstract:
Curcumin, the active constituent of the rhizome Curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is constrained due to poor absorption, rapid metabolism, degradation in acidic media and consequently, low oral bioavailability. In the present study, we aim to formulate a curcumin-containing mucoadhesive nanoparticulate delivery system that offers protection to curcumin from the degradative effects of the upper digestive tract system but capable of releasing the payload in the colon for the localised treatment of colorectal cancer. Such a system should have a good surface coverage locally at the tumour site and ideally, capable of traversing the tumour. Thus, nanopariculate delivery is most suited to achieve this objective. The latter was formulated using chitosan and pectin as polymers due to their biodegradability and non-toxicity. The objectives of this study were (i) to fabricate, optimize and characterize the curcumin-containing delivery system; (ii) to evaluate the mucoadhesive propensity, release of curcumin from the carrier, and stability of the formulation in various milieu; (iii) to investigate the in vitro antiproliferative efficacy of the formulation as well as the cellular uptake profiles; and (iv) to proof the concept of the formulation using animal modules. The formulated nanoparticulate system had a z-average of 206.0 nm (± 6.6 nm), zeta potential of +32.8 mV (±0.5 mV), and encapsulation efficiency of 64%. The nanoparticles were more mucoadhesive at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in simulated colonic medium as opposed to negligible release in simulated gastric and intestinal fluids, respectively. The nanoparticles were taken-up by HT-29 colorectal cancer cells which ultimately resulted in a tremendous reduction in cell propagation. This anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not affect the anticancer efficacy of curcumin. The bioavailability of curcumin from the nanoparticles was enhanced by 4-folds after oral administration after 6 hr of treatment. Moreover, the half-life, Cmax, and AUC of curcumin were significantly improved. A lower elimination rate was observed from the formulation compared to equivalent doses of free curcumin. These findings are a strong indication of the potential of the studied formulation for the possible treatment of colon cancer via oral administration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.757475  DOI: Not available
Keywords: RM Therapeutics. Pharmacology
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