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dc.contributor.advisorDash, Alekhaen_US
dc.contributor.authorJauhari, Saurabhen_US
dc.date.accessioned2014-06-17T13:33:22Z
dc.date.available2017-06-06T08:40:19Z
dc.date.issued2006-08en_US
dc.identifier.urihttp://hdl.handle.net/10504/55686
dc.description.abstractMUC1 gene encodes a transmembrane mucin glycoprotein that is over expressed in human breast cancer and colon cancer. The underlying hypothesis of this investigation was that a mucoadhesive in situ gel delivery system containing paclitaxel (PTX) can be targeted to the cancer cells where MUC 1 gene is over expressed as compared to normal cells. The objective of this study was to develop an in situ gel delivery system containing PTX and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX.|A sensitive LC method was developed and validated for the analysis of the drug. The chromatographic separation was achieved using a ZORBAX SB C-18 column (150x4.6 mm, 5p). Mobile phase consisted of acetonitrile:methanol:0.1M ammonium acetate (48.5:16.5:35, v/v/v). The within day and day-to-day precision, relative standard deviation (RSD) for this assay range from 0.66 to 8.04% and 4.14 to 10.6%, respectively. The critical level, the detection level and the determination level for this method were, 0.02±0.01 pg/mL (mean±S.D, n=6), 0.04±0.02 pg/mL (mean±S.D, n=6), and 0.11±0.05 pg/mL. (mean±S.D, n=6), respectively. This method was successfully used in the evaluation of the in vitro release characteristics, homogeneity of PTX in gel formulation, and in the quantitation of PTX during transport studies.|The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18, 0 30, and 0.54% (w/w), in Sorensen’s phosphate buffer (pH=7.4) at 37°C. The in vitro release studies were carried out under sink condition. For determining the drug load, one mL of the delivery system was added to 50 mL of Sorensen’s phosphate buffer, or appropriate solvent, and sonicated over a period of 10-15 minutes. The solution was filtered through a Nylon syringe filter (0.45 jam) and the concentration of drug in the solution was measured by HPLC. In vitro release studies revealed that within four hours, only 7.61 ±0.19, 12.0±0.98, 31.7±0.40% of PTX were released from 0.18, 0.30, and 0.54% PTX loaded gel formulation, respectively in absence of Tween 80. However, in the presence of the surfactant (0.05% w/v) in the dissolution medium, PTX release were 28.1±4.35, 44.2± 6.35, and 97.1±1.22%, respectively.|Different mucin producing cell lines (Calu-3>Caco-2) were selected for the PTX transport studies. Transport of PTX from solution and gel delivery system was carried out in side-by-side diffusion chambers from apical to basal (a-b) and basal to apical (b-a) directions. PTX showed a polarized transport in all of the cell monolayers with b-a transport being 2-4 times higher than a-b direction. The highest mucin producing cell line (Calu-3) has shown the least PTX transport from gels as compared to Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by mucin producing capability of cell.|The future goals of this investigation will be to compare the effectiveness of targeted local in situ gel delivery system versus the systemic delivery and to evaluate the local tissue and organ toxicity of the delivery system. This will include in vitro and in vivo evaluation of taxoi delivery system using a murine breast cancer model (Clone-66) consisting of immunocompetent host and human breast cancer model (MDA-231 and MDA-453) consisting of immunodeficient mice.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_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.subject.meshDrug Delivery Systems--methodsen_US
dc.subject.meshMucous Membrane--metabolismen_US
dc.subject.meshPaclitaxel--administration & dosageen_US
dc.subject.meshPaclitaxel--pharmacokineticsen_US
dc.subject.meshTissue Adhesives--chemistryen_US
dc.titleA Mucoadhesives in Situ Gel Delivery System for Paclitaxel.en_US
dc.typeThesis
dc.rights.holderSaurabh Jauharien_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesxxi, 151 pagesen_US
dc.contributor.cuauthorJauhari, Saurabhen_US
dc.embargo.liftdate2100-01-01
dc.embargo.terms2100-01-01
dc.degree.levelMS (Master of Science)en_US
dc.degree.disciplinePharmaceutical Science (graduate program)en_US
dc.degree.nameM.S. in Pharmaceutical Sciencesen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeMakoid, Michaelen_US
dc.degree.committeeSingh, Somnathen_US


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