Wang, Shu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 119-139). / Abstracts in English and Chinese. / Table of contents --- p.i / Abstract --- p.v / 摘要 --- p.viii / Acknowledgements --- p.x / List of tables --- p.xi / List of figures --- p.xiii / List of abbreviations --- p.xvi / Chapter Chapter One. --- Introduction --- p.1 / Chapter 1.1 --- Overview of nasal drug delivery --- p.2 / Chapter 1.1.1 --- Structure and permeability of the nasal mucosa --- p.3 / Chapter 1.1.2 --- Pathways of drug permeation across nasal mucosa --- p.6 / Chapter 1.1.3 --- Models for nasal drug permeation studies --- p.7 / Chapter 1.1.3.1 --- In vitro models --- p.7 / Chapter 1.1.3.2 --- In situ models --- p.13 / Chapter 1.1.3.3 --- In vivo animal models --- p.16 / Chapter 1.1.4 --- Factors affecting drug absorption across nasal mucosa --- p.19 / Chapter 1.1.4.1 --- Biological factors --- p.20 / Chapter 1.1.4.2 --- Physicochemical properties of drugs --- p.25 / Chapter 1.1.4.3 --- Formulation factors --- p.29 / Chapter 1.1.5 --- Profile of a suitable drug candidate for nasal delivery --- p.33 / Chapter 1.2 --- Physicochemical properties and human pharmacokinetics of the four drug candidates --- p.35 / Chapter 1.2.1 --- Rizatriptan --- p.35 / Chapter 1.2.2 --- Meloxicam --- p.37 / Chapter 1.2.3 --- Lomoxicam --- p.39 / Chapter 1.2.4 --- Nebivolol --- p.40 / Chapter 1.3 --- Scope of the current study --- p.44 / Chapter Chapter Two. --- Preliminary validation of Calu-3 cell line model as an in vitro model for nasal drug permeation screening --- p.45 / Chapter 2.1 --- Introduction --- p.45 / Chapter 2.2 --- Materials --- p.46 / Chapter 2.2.1 --- Chemicals --- p.46 / Chapter 2.2.2 --- Materials for cell culture --- p.46 / Chapter 2.2.3 --- Instruments --- p.47 / Chapter 2.3 --- Methods --- p.47 / Chapter 2.3.1 --- Cell culture --- p.47 / Chapter 2.3.2 --- Cytotoxicity studies by MTS/PES assay --- p.48 / Chapter 2.3.2.1 --- Optimization of MTS/PES assay for the initial cell seeding density and the incubation time --- p.49 / Chapter 2.3.2.2 --- Cytotoxicity studies of non-physiological pH and osmolarity on Calu-3 cells by MTS/PES assay --- p.49 / Chapter 2.3.3 --- Integrity of Calu-3 cell monolayers --- p.50 / Chapter 2.3.3.1 --- Transepithelial electrical resistance (TEER) --- p.50 / Chapter 2.3.3.2 --- Permeabilities of marker compounds --- p.51 / Chapter 2.3.3.3 --- Effect of osmolarity on the Calu-3 cell monolayers --- p.53 / Chapter 2.3.4 --- Inter-passage variation --- p.53 / Chapter 2.3.5 --- Statistical analysis --- p.54 / Chapter 2.4 --- Results and discussions --- p.54 / Chapter 2.4.1 --- Cell culture --- p.54 / Chapter 2.4.2 --- Cytotoxicity studies by MTS/PES assay --- p.55 / Chapter 2.4.2.1 --- Optimization of MTS/PES assay for the initial cell seeding density and the incubation time --- p.55 / Chapter 2.4.2.2 --- Cytotoxicity studies of non-physiological pH and osmolarity on Calu-3 cells by MTS/PES assay --- p.57 / Chapter 2.4.3 --- Integrity of Calu-3 cell monolayers --- p.58 / Chapter 2.4.3.1 --- Transepithelial electrical resistance (TEER) --- p.59 / Chapter 2.4.3.2 --- Permeabilities of marker compounds --- p.60 / Chapter 2.4.3.3 --- Effect of osmolarity on the Calu-3 cell monolayer --- p.63 / Chapter 2.4.4 --- Inter-passage variation --- p.65 / Chapter 2.5 --- Conclusion --- p.66 / Chapter Chapter Three. --- Permeation studies of selected drug candidates using the Calu-3 cell line model --- p.68 / Chapter 3.1 --- Introduction --- p.68 / Chapter 3.2 --- Materials --- p.69 / Chapter 3.2.1 --- Chemicals --- p.69 / Chapter 3.2.2 --- Materials for cell culture --- p.69 / Chapter 3.2.3 --- Instruments --- p.69 / Chapter 3.3 --- Methods --- p.70 / Chapter 3.3.1 --- HPLC assay development and validation for the drug candidates --- p.70 / Chapter 3.3.2 --- Stabilities of the drug candidates in loading solutions at different pHs --- p.71 / Chapter 3.3.3 --- Cell culture --- p.71 / Chapter 3.3.4 --- Cytotoxic effects of the drug candidates on Calu-3 cells by MTS/PES assay --- p.71 / Chapter 3.3.5 --- Permeation studies of drug candidates using Calu-3 cell line model --- p.72 / Chapter 3.3.5.1 --- Effect of concentration on the permeabilities of drug candidates across Calu-3 cell line model --- p.72 / Chapter 3.3.5.2 --- Effect of pH on the permeabilities of drug candidates across Calu-3 cell line model --- p.73 / Chapter 3.3.5.3 --- Effect of osmolarity on the permeabilities of drug candidates across Calu-3 cell line model --- p.73 / Chapter 3.3.6 --- Permeation studies of drug candidates in artificial membrane model at different pHs --- p.73 / Chapter 3.3.7 --- Correlation of the permeabilities of drug candidates between Calu-3 cell line model and artificial membrane model --- p.74 / Chapter 3.3.8 --- Statistical analysis --- p.75 / Chapter 3.4 --- Results and discussions --- p.75 / Chapter 3.4.1 --- HPLC methods for the drug candidates --- p.75 / Chapter 3.4.2 --- Stabilities of the drug candidates in loading solutions at different pHs --- p.75 / Chapter 3.4.3 --- Cytotoxic effects of the drug candidates on Calu-3 cells by MTS/PES assay --- p.76 / Chapter 3.4.4 --- Permeation studies of drug candidates in Calu-3 cell line model --- p.81 / Chapter 3.4.4.1 --- Effect of concentration on the permeabilities of drug candidates across Calu-3 cell line model --- p.81 / Chapter 3.4.4.2 --- Effect of pH on the permeabilities of drug candidates across Calu-3 cell line model --- p.84 / Chapter 3.4.4.3 --- Effect of osmolarity on the permeabilities of drug candidates across Calu-3 cell line model --- p.87 / Chapter 3.4.5 --- Permeation studies of drug candidates in artificial membrane model at different pHs --- p.88 / Chapter 3.4.6 --- Correlation of the permeabilities of drug candidates between Calu-3 cell line model and the artificial membrane model --- p.92 / Chapter 3.5 --- Selection of drug candidate for further in vivo studies --- p.93 / Chapter 3.6 --- Conclusion --- p.93 / Chapter Chapter Four. --- In vivo absorption studies of the most promising drug candidate --- p.95 / Chapter 4.1 --- Introduction --- p.95 / Chapter 4.2 --- Materials --- p.96 / Chapter 4.2.1 --- Chemicals --- p.96 / Chapter 4.2.2 --- Instruments --- p.96 / Chapter 4.3 --- Methods --- p.97 / Chapter 4.3.1 --- HPLC conditions --- p.97 / Chapter 4.3.2 --- Preparation of standard solutions --- p.97 / Chapter 4.3.3 --- Calibration curves --- p.98 / Chapter 4.3.4 --- Sample preparations --- p.98 / Chapter 4.3.5 --- Validation of the assay method --- p.98 / Chapter 4.3.5.1 --- Specificity --- p.98 / Chapter 4.3.5.2 --- Precision and accuracy --- p.99 / Chapter 4.3.5.3 --- Recovery --- p.99 / Chapter 4.3.5.4 --- Sensitivity --- p.99 / Chapter 4.3.5.5 --- Stability --- p.99 / Chapter 4.3.6 --- Animals --- p.100 / Chapter 4.3.7 --- Drug administration --- p.102 / Chapter 4.3.8 --- Data analysis --- p.102 / Chapter 4.4 --- Results and discussions --- p.103 / Chapter 4.4.1 --- Validation of the assay method --- p.103 / Chapter 4.4.1.1 --- Specificity --- p.103 / Chapter 4.4.1.2 --- "Precision, accuracy and linearity" --- p.105 / Chapter 4.4.1.3 --- Recovery --- p.106 / Chapter 4.4.1.4 --- Sensitivity --- p.107 / Chapter 4.4.1.5 --- Stability --- p.108 / Chapter 4.4.2 --- "In vivo absorption studies through the nasal, intravenous and oral routes in rat model" --- p.108 / Chapter 4.4.3 --- Preliminary correlation between permeabilities of compounds in Calu-3 cell line model and their nasal bioavailabilities in animal models --- p.111 / Chapter 4.5 --- Conclusion --- p.113 / Chapter Chapter Five. --- Overall conclusion --- p.114 / Chapter Chapter Six. --- Future studies --- p.117 / References --- p.119
Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_326669 |
Date | January 2009 |
Contributors | Wang, Shu., Chinese University of Hong Kong Graduate School. Division of Pharmacy. |
Source Sets | The Chinese University of Hong Kong |
Language | English, Chinese |
Detected Language | English |
Type | Text, bibliography |
Format | print, xvi, 139 leaves : col. ill. ; 30 cm. |
Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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