Surface Modified Solid Lipid Curcumin Nanoparticles For Oral Delivery

dc.contributor.advisorDash, Alekha K.en_US
dc.contributor.authorMistry, Pinalen_US
dc.contributor.cuauthorMistry, Pinalen_US, Somnathen_US, Justin A.en_US Science (graduate program)en_US Schoolen_US (Master of Science)en_US in Pharmaceutical Sciencesen_US
dc.description.abstractCurcumin is a naturally available polyphenolic compound that has demonstrated chemotherapeutic effects in several carcinogenic models as well as pre-clinical trials. However, its poor oral bioavailability due to extremely low aqueous solubility, poor permeability and extensive pre-systemic metabolism has been the major limitation for its use as a chemotherapeutic agent. Solid lipid nanoparticulate formulations have been successfully used to enhance the oral bioavailability of several poorly soluble drugs. The objective of the present research was to develop and characterize solid lipid nanoparticles for oral delivery of curcumin using GMO/chitosan based nanoparticulate system containing two different stabilizers. |The oil/water nanoemulsions were prepared by sonication and high pressure homogenization (HPH) using GMO/chitosan system. Two different stabilizers namely, PVA and poloxamer 407 were used for this purpose. The particles size (PS) and zeta potential (ZP) of nanoemulsion were determined at different stages of preparation using zetameter. The physical stability of the nanoemulsion was studied at 25⁰C over a period of 60 days by determining its PS and ZP. The blank and curcumin loaded nanoemulsions of both PVA as well as poloxamer containing formulations were further lyophilized and characterized for PS and ZP. The surface morphology of drug loaded nanostructures was determined using scanning electron microscopy. The weight loss of these formulations on heating was investigated using thermogravimetry while the moisture content was determined using Karl Fischer titrimetry. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis was performed to determine the physical state of the drug in the nanostructures. An UPLC method was developed and validated for the analysis of curcumin. The in vitro release of curcumin from the nanostructures was evaluated at 37⁰C in pH 7.4 buffer containing 0.5% (w/v) Tween 80 by using UPLC. The cellular uptake of curcumin from the solution as well as nanostructures was investigated in Caco-2 cells after 30, 60 and 90 minutes of treatment. |The process of HPH effectively reduced the particle size of the curcumin loaded GMO/chitosan nanoemulsions by 50 to 65% after three cycles. Loading the GMO/chitosan system with a hydrophobic drug caused an increase in its particle size. Poloxamer 407 was found to be a more efficient stabilizer as compared to PVA to stabilize the GMO/chitosan nanostructures because it gives stable nanoemulsions at a % (w/v) concentration five times less than PVA. The DSC and XRD studies confirmed the crystalline nature of drug in the nanostructures and showed that the absence of visible thermal events in the DSC thermograms could be misleading if two opposite thermal events occur at the same temperature range. Use of poloxamer as a stabilizer sustained the curcumin release from the nanostructures when compared with PVA. The percent cumulative release of curcumin from the nanoparticulate formulation with PVA and poloxamer after 171 hours was found to be 73.93 ± 5.25 and 53.15 ± 5.84, respectively. The cellular uptake of curcumin was 2.5-fold higher in nanostructures containing PVA as compared to poloxamer, at all the time points tested. Appropriate selection of stabilizer for the fabrication of GMO/chitosan nanoparticulate system can affect its ZP, surface morphology, rates of release and cellular uptake in Caco-2 cells. However, the PS, moisture content, and physical state of the drug in the system, was unaffected by the type of stabilizers tested.en_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxvii, 82 pagesen_US
dc.identifier.otherPinal Mistry Final thesis.pdf
dc.publisherCreighton Universityen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.rights.holderPinal Mistryen_US
dc.subject.meshCurcumin--administration & dosageen_US
dc.subject.meshAntineoplastic Agents--administration & dosageen_US
dc.subject.meshDrug Carriers--chemistryen_US
dc.titleSurface Modified Solid Lipid Curcumin Nanoparticles For Oral Deliveryen_US
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