Development of novel formulations for mucosal delivery of protein ...

More documents

Recommendations

Info

ACKNOWLEDGEMENTS First and foremost, I would like to take this opportunity to thank the almighty God for His loving kindness and faithfulness in sustaining my life all these years. I am nothing without you my Lord and saviour Jesus Christ. I love you with my heart, mind and soul. Thanks to Dr. Joshua Boateng for your patience, understanding and guidance, not just as a supervisor but as a brother. You always knew what I needed and when. You understood the tension between family and school and never faltered. Thanks Boss. Prof. J. Mitchell, I greatly appreciate the fatherly manner you have guided me through my PhD experience. Thank you for being there when it mattered most. A big thank you to my research group members; Dr. Farnoosh Kianfar, Dr. Concetta Giovino and Mr. Harshavardhan Pawar for all your guidance and support. Harsh, thank you for your selfless help during the latter parts of my work. I am also grateful to Dr. Ian Slipper for all the SEM and XRPD techniques. Thanks and love to Olivia my wife for representing constant love and support for the last 8 years of my life. I love you. Thanks to Irene and Kezia for your smiles and understanding of what it means when ‘daddy has to do his passion’ and for giving me the good reasons to stop when it was time to read the Bible, your story books and to listen to your readings. I have cherished every moment we’ve shared together as a family. You all deserve this PhD award and I therefore dedicate this piece of work to you; Olivia, Irene, Kezia and to our unborn child (Little Olivia). I would want to thank my family and that of my wife for the inspiration and belief. I cannot fail to mention the spiritual support of friends at Kingdom Exchange Ministries. Pastor Emmanuel Oladipo and family, Dr. Bernasko and family, Mr. Josiah Reindorf and Family, Mr Kwarshie-Annang and Family, Mr. Emmanuel Asiedu, Mr. David Larkai and Miss Jemima Wiafe -thank you all for your care and encouragement. Finally I would like to thank the Commonwealth Scholarships Commission for fully sponsoring the entire doctoral studies in addition to paying my stipend and family allowances. I am also grateful to the School of Science, University of Greenwich for the top-up bursary during the latter stages of my studies and KNUST for the study leave.
ABBREVIATIONS ATR-FT-IR (attenuated total reflection-Fourier transform infra-red); APR (aprotinin); BSA (bovine serum albumin); CD (circular dichroism); DSC (differential scanning calorimetry); DTT (dithiothreitol); EDAC (N-(3-Dimethylaminopropyl)-N-ethyl carbodiimide hydrochloride); EI (enzyme inhibitor); GPC (gel permeation chromatography); GSH (reduced glutathione); HPLC (high-performance liquid chromatography); ICH (International Conference on Harmonisation); INS (insulin) NaAc (sodium acetate); NMR (nuclear magnetic resonance); PAF (peak adhesive force); PBS (phosphate buffered saline); PE (permeation enhancer); RH (relative humidity); SEM (scanning electron microscopy); TA (texture analyser); TGA (thermo-gravimetric analysis); TG (thioglycolic acid); TWA (total work of adhesion); XRPD (X-ray powder diffraction)
Page 1 and 2: Greenwich Academic Literature Archi
Page 3: DECLARATION “I certify that this
Page 7 and 8: CONTENTS DECLARATION ..............
Page 9 and 10: CHAPTER TWO .......................
Page 11 and 12: CHAPTER FOUR ......................
Page 13 and 14: TABLES Table 1.1: Relationship of i
Page 15 and 16: FIGURES Figure 1.1: Molecular model
Page 17 and 18: [Accessed; 24/05/2012]. ...........
Page 19 and 20: Figure 4.2: In-vitro mucoadhesion m
Page 21 and 22: CHAPTER ONE INTRODUCTION AND LITERA
Page 23 and 24: freezing rate at the start of a lyo
Page 25 and 26: aggregates may lead to an immunogen
Page 27 and 28: Figure 1.1: Molecular model of seru
Page 29 and 30: One of the greatest milestones in m
Page 31 and 32: limited success. INS released in a
Page 33 and 34: composition of the delivery system
Page 35 and 36: ioavailability of proteins using pe
Page 37 and 38: 1.3.3.2 Factors affecting mucoadhes
Page 39 and 40: Human salivary glands secrete 1000-
Page 41 and 42: 1.4.2 The nasal route Nasal protein
Page 43 and 44: 1.4.3 The pulmonary route The lungs
Page 45 and 46: and enzymes from foods and beverage
Page 47 and 48: (Veuillez et al., 2001; Nagai, 1986
Page 49 and 50: 1.6.1 Chitosan Chitosan together wi
Page 51 and 52: 1.6.3 Chitosan derivatives The exce
Page 53 and 54: with increasing amounts of immobili
Page 55 and 56:
1.6.6.3 Thiolated chitosans as matr
Page 57 and 58:
stability studies among others can
Page 59 and 60:
the product matrix, the vacuum of t
Page 61 and 62:
an oven at an appropriate temperatu
Page 63 and 64:
Several analytical procedures have
Page 65 and 66:
transmitting crystal with a high re
Page 67 and 68:
1.8.4.2 Powder diffraction Powder X
Page 69 and 70:
1.8.5.1 Interpreting DSC thermogram
Page 71 and 72:
(absorption in the range 260 to 320
Page 73 and 74:
Figure 1.26: Representation of SEM.
Page 75 and 76:
CHAPTER TWO FORMULATION DEVELOPMENT
Page 77 and 78:
have recommended annealing time of
Page 79 and 80:
Figure 2.1: Chemical structure of c
Page 81 and 82:
model proteins for buccal delivery.
Page 83 and 84:
microemulsion formulation containin
Page 85 and 86:
Table 2.2: Details of consumables u
Page 87 and 88:
chitosan was stirred continuously f
Page 89 and 90:
Table 2.5: Lyophilisation cycles wi
Page 91 and 92:
a b c d Figure 2.6: Photographs of
Page 93 and 94:
simple one step coupling reaction i
Page 95 and 96:
2.3.5 Lyophilisation The primary dr
Page 97 and 98:
The foremost implication of these f
Page 99 and 100:
3.2 Materials and methods 3.2.1 Mat
Page 101 and 102:
were analysed with Agilent Chemstat
Page 103 and 104:
previously tarred 70 µl aluminium
Page 105 and 106:
3.2.13.2 Assay of BSA and INS conte
Page 107 and 108:
A H1 (GluNAc) H3 -H6 NAc H2 (GluNH
Page 109 and 110:
V o V e Intensity ElutionTime (min)
Page 111 and 112:
c c r er % Transmittance 110 90 70
Page 113 and 114:
during the xerogel preparation proc
Page 115 and 116:
and without APR respectively. The r
Page 117 and 118:
3.3.7 Physical stability of BSA and
Page 119 and 120:
15 Circular dichroism (mdeg) 10 5 0
Page 121 and 122:
Since no product melt-back was obse
Page 123 and 124:
0.8 Absorbance ratio 595/450 0.7 0.
Page 125 and 126:
A B Dialysed chitosan-BSA 100 µm 1
Page 127 and 128:
High magnification SEM micrograph o
Page 129 and 130:
BSA content (%) 100.0 80.0 60.0 40.
Page 131 and 132:
conditions leads to protein hydroly
Page 133 and 134:
3.4 Conclusions Analytical characte
Page 135 and 136:
CHAPTER FOUR HYDRATION CAPACITY AND
Page 137 and 138:
4.2.2.1 Effect of formulation proce
Page 139 and 140:
substrate in order to select the op
Page 141 and 142:
Table 4.3 Hydration capacity of xer
Page 143 and 144:
4.3.2.1 Factors affecting mucoadhes
Page 145 and 146:
impacted on the mucoadhesive proper
Page 147 and 148:
and TG-chitosan xerogels. The chito
Page 149 and 150:
PAF (N) TWA (mJ) Cohesiveness (mm)
Page 151 and 152:
Annealed TG-chitosan xerogel simila
Page 153 and 154:
that each model makes assumptions t
Page 155 and 156:
independent difference and similari
Page 157 and 158:
elease profiles plotted. Blank cont
Page 159 and 160:
the second phase of the release pro
Page 161 and 162:
100 Cummulative BSA Release (%) 80
Page 163 and 164:
controlled drug release has been de
Page 165 and 166:
Cummulative INS release (%) 100 80
Page 167 and 168:
that of non-annealed dialysed chito
Page 169 and 170:
Table 5.5: Release parameters obtai
Page 171 and 172:
The effect of formulation processes
Page 173 and 174:
Table 5.9: Model independent differ
Page 175 and 176:
CHAPTER SIX PERMEATION STUDIES USIN
Page 177 and 178:
6.2 Materials and Methods 6.2.1 Mat
Page 179 and 180:
Permeation studies were conducted f
Page 181 and 182:
fold increase in transport of BSA f
Page 183 and 184:
Cumulative INS permeated (g/cm 2 )
Page 185 and 186:
Average percentage viability was pl
Page 187 and 188:
5.5 A TG-chitosan-INS permeation (E
Page 189 and 190:
CHAPTER SEVEN SUMMARY CONCLUSIONS A
Page 191 and 192:
was observed for dialysed and annea
Page 193 and 194:
2. The long-term stability evaluati
Page 195 and 196:
drug delivery systems via the bucca
Page 197 and 198:
33. Bunte, H., Drooge, D.J., Ottjes
Page 199 and 200:
56. Engles, L. 2005. Review and app
Page 201 and 202:
(chitooligosaccharide derivatives)
Page 203 and 204:
of single-point mutants of an amylo
Page 205 and 206:
121. Koschier, F., Kostrubsky, V.,
Page 207 and 208:
142. Liu, W., Wang, D.Q., Nail, S.
Page 209 and 210:
160. Modi, P., Mihic, M. And Lewin,
Page 211 and 212:
180. Pastore, A., Piemonte, F., Loc
Page 213 and 214:
204. Robinson, J., R. 1990. Rationa
Page 215 and 216:
224. Silva, C.A., Nobre, T.M., Pavi
Page 217 and 218:
245. Tamburic, S., Graig, D.Q.M. 19
Page 219 and 220:
265. Wang W. 2000. Lyophilisation a
Page 221 and 222:
285. Zor, T., Selinger, Z. 1996. Li
Page 223 and 224:
APPENDIX B: Manuscripts in preparat
Page 225 and 226:
2. Accepted abstract for podium and
Page 227 and 228:
4. Abstract # 43 awarded podium and
Page 229 and 230:
6. Published abstract M1144 (2011).
Page 231:
8. Published abstract W1470 (2010).
show all

Development of novel formulations for mucosal delivery of protein ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?