Index

Acid hydrolysis, activation energy for, 270

Acid-labile formulations for lipoplexes, synthesis and advantages of, 139

Acid-labile system, mechanism, 159 Acid-sensitive lipoplexes pH-degradable cationic lipids, 142 pH-degradable polyethylene glycol

lipids, 149-155 Acid-triggered content leakage assay, 174 Acylhydrazone linker, 156 Acylhydrazone-linked guanidinium

cationic lipids, 176 Adenovirus (AV) vector, 98 Aeroneb Pro, 80, 82 Aerosols impingers for, 72-74 nebulizer-produced, 69 non-respirable, 78 production and characterization

of, 72 respirable, 78 size measurement, 72, 75

Agarose gel electrophoresis, 105 Aggregation/micellization and

deaggregation/demicellization enthalpy, 214

Air-blast nebulizers. See Jet nebulizers Air-jet nebulizers. See Jet nebulizers

Alcohol-based proliposomes, 71 nebulization of, 80-81

Alcohol injection method, 42 advantages of, 43

a-Amino-x-methoxy-PEG, 150 a-Hemolysin, 188 Ambisome1, 122, 261, 306 median diameter of, 309 titration of, 307 See also Liposomal amphotericin

B product Amine-influenced hydrolysis, 289 Amphiphiles, pH-sensitive, 169 Amphiphiles, self-assembly of, 197-198 Anhydrobiosis, 261 Anion exchange high performance

liquid chromatography (AIEX-HPLC), 105

Antigen delivery by virosomes, 85, 89-90

Antigen-presenting cells (APC), 85 Arbutin, 266 inhibition of PLA2 activity

by, 272-273 Artificial virus, 188-191 efficient gene transfer by, 189 formation of, 189 sequential assembly of, 189-191 transfection activity of, 189

B-cell epitopes, advantages of, 89 Bafilomycin A, 148 b-Mercaptoethanol, 177 BGBHcholest-4-enone, pH-labile, 156 Bilayer permeability, effect of hydrolysis

on, 289 Bilayer stability, effect of hydrolysis

on, 289 Bilayer stabilization, 14 Bilayered phospholipids fragments

(BPFs), 209 visualization of, 217

Bile salt, as masking agent, 48 Bile salt micelles, solubilization

effect, 234 Bioresponsive liposomes, 165 definition of, 166 multifunctional, 189-191

Brownian collisions, 298

Caelyx1, 122 Calcein diffusion of, 248 oil solution formulations, 49 release from oil phase, 50

Camptothecin, cytostatic, 289 Caprylic/capric triglyceride

(MCT), 44 Carboplatin, 248 Cationic lipid-based gene delivery

systems, 108-109 Cationic lipid/DNA complex fluorescence resonance energy transfer

(FRET) technique in, 109 formation, 109

Cationic lipids, pH-labile, 141-142, 155-157

chemistry, 142-143 degradation studies, 145-147 DNA compaction in, 143-145 DNA liberation by, 144 physicochemistry of, 143 and stable analogs, 142-143 synthesis and synthetic pathways

of, 142-145 transfection experiments in, 147

Cationic lipids, pH-sensitive synthesis of, 169

Cellular immune response, 90-91 of virosomes, 87

Cernevit1MM, 234 Cetrorelix1, 248 Cetyl poly(ethylenimine) amphiphiles,

202 Chinese hamster ovary (CHO) cells, 185 Chitosan, 200 Chlorofluorocarbons (CFCs), 69 Cholesterol-based reducible cationic

lipids, 179 Cholesterol-based reduction-responsive

lipids, 184 Cholesterol phosphate derivatives,

187-188 Cholesteryl chloroformate, 150 Cholesteryl PEG, 150 Chromobacterium viscosum lipase, 15 CMC. See Critical micelle concentration Coacervation method, in liposome

preparation, 22-24, 31-32 CONTIN program, 227 Critical aggregation concentration. See

Micelles, critical micelle concentration

Critical concentration of vesicle formation (CVC), 2

Critical micelle concentration (CMC), 211

of detergents, 183, 214 sodium oleate, 215

Cryo-TEM. See Cryo-transmission electron microscopy

Cryo-transmission electron microscopy (cryo-TEM)

in mixed lipid-detergent systems, 210 to visualize CMMs, 217

Cryoprotectants, 115 Cylindrical mixed micelles (CCMs),

209, 217 Cystic fibrosis (CF), 120 Cytomegalovirus (CMV), 143 Cytotoxic T cell (CTL) epitopes, 90 immune response, 91

D/max 2400 Diffractometer, 37 DaunoXome1, 42, 122 Demicellization/deaggregation

protocol, 211-212 Deoxycholate-amphotericin B

suspension and AmBisome, comparison, 306-307

dePEGylation strategy, 187 dePEGylation triggering, 168 Detergent(s) concentration, 220 electrostatic shielding effect of, 222 lipids and water, 210 partition coefficient of, 217 calculation of, 221 definition of, 218 surface potential and, 220 thermodynamic parameters for, 221

Detergent dialysis techniques, 56 Detergent partitioning into vesicles,

217-223 Detergent-versus-lipid phase

diagram, 229 dFdC a anticancer agent, 254 antitumoral activity of, 254 half-life of, 254 liposomal entrapment of, 254

Diacyl phosphatidylcholine vesicles, 1 fatty acid vesicles and, 2

Diarachidoyl PC (DAPC), 63 Differential scanning calorimetry (DSC),

112, 272 Dimyristoyl phosphatidylcholine

(DMPC), 232 Diol-silica columns, 286 1,2-Dioleoyl glycero-3-phospha-

tidylcholine (DOPC), 185 transgene expression enhancement

by, 185 1,2-Dioleoyl-3-trimethylammonium-

propane (DOTAP), 176 1,2-Dioleoyl-sn-glycero-3-phospha-

tidylethanolamine (DOPE) liposomes, 168

colipid, 143 fusogenic lipid, 187

Dioxazocinium ortho esters, 169 hydrolysis of, 172-173

Dipalmitoyl phosphatidylcholine (DPPC), 37, 73, 221-222

phase diagrams for solubilization of, 231

1,6-Diphenyl-1,3,5-hexatriene (DPH), 223

Diphtheria toxin-neutralizing antibodies, 88

Diphtheria-virosomes, 88 Distamycin, 190 Disulfide linkage, 178 Disulfide-linked gemini cationic

lipids, 179 Dithiobis(succinimidyl propionate), 178 Dithiothreitol (DTT), 177 reduction of disulfides by, 184 as thiolytic reagent, 183

DNA compaction, 144 endosome release, 177 minor-groove-binding reagent, 190

Dodecylmaltoside (water), demicellization of, 215

Domains in dry state, maintenance of, 274-278

DOPE. See 1,2-dioleoyl-sn-glycero-3phosphatidylethanolamine

DOPE/DPPC vesicles, 289 DOPE/lipid combination, 289 DOTAP/DOPE, DOPE hydrolysis

in, 289 Doxil, 301. See Liposomal doxorubicin

(DOX) product Doxil1, 122 Doxil1/Caelyx1, 42 Doxorubicin, 94, 206 DPPC. See 1,2-dipalmitoyl-sn-glycero-3-

phosphocholine DPPC/chol liposomes, 73 hydrophilic, 43 loading approach of, 41-42 release behavior, 49

Drug delivery systems, pulmonary, 67 to respiratory tract by, 67-68

[Drug delivery] dry powder inhalers, 69 nebulizers, 69 pressurized metered dose

inhalers, 69 Drug-lipid complexes, 122 Drug-loaded liposomes, 285 polyethyleneglycol (PEG)-coated

liposomes in, 287 Dry powder inhalers (DPIs), 69 Dynamic light scattering. See Photon

correlation spectroscopy

Effective edge tension, 216-217 Egg PC. See Egg phosphatidylcholine Egg phosphatidylcholine (Egg PC) liposomes, 72, 78 MLV, 59 multilamellar liposome, 60

Elastase-responsive liposomes, 187 Ellipsoidal mixed micelles

(EMMs), 209 ELSD. See Evaporative light scattering

detectors Enzyme-responsive liposomes,

186-189 for drug and gene delivery, 188

Epaxal, 91, 93 Escherichia coli cultivation of, 103 fermentation of, 101 host strain, 101 in pDNA manufacture, 101

Ethanol injection technology orientatation of, 28 use of solvent form of, 28 vesicles, 216 liposome preparations, 28, 42

Ethidium bromide (EtBr), 143 Euregenethy 2 network, objectives

of, 124 Evans’ method of liposome

preparation, 42 Evaporative light scattering detectors

(ELSD), 286 Extruder, 56

[Extruder] features of, 56-57 See also Extrusion device

Extrusion applications of, 64 advantages of, 60 biophysical aspects of, 58 device, 56 of diarachidoyl PC (DAPC), 63 distearoyl PC (DSPC), 63 filter surface area, 62, 64 and lipid composition, 61-64 in liposomal drug delivery, 58 liposome, 61, 63 mechanism of, 58 membrane rupture and resealing, 58 of MLV, 56, 62 nitrogen gas in, 56 unilamellar vesicles and,

55-58 vesicle formation, 58

Fatty acid liposomes. See Fatty acid vesicles

Fatty acid/soap bilayers, surface potential of, 2

Fatty acid/soap vesicles, 7 formation of, 6-7 Gibbs phase rule in, 9 titration curves for, 7 transition of aggregates in, 7-9

Fatty acid vesicles, 1 applications of, 15-17 bilayer-monomer equilibrium

of, 14-15 diacyl phospholipid vesicles and, 2 entrapment of water soluble

compounds in, 14-15 experimental conditions for formation

of, 13 formation general conditions for, 6-7 pathways, 10-12

in human skin, 16-17 interaction at solid surfaces, 16 long-chain, 2

[Fatty acid vesicles] matrix effect by, 16 model compartments for protocells,

15-16 physical stabilization of, 14 in prebiotic chemistry, 16 preparation of, 10-12 properties of, 2, 12-15 short-chain, 5 solubility and critical concentration

of, 14 unique characteristics of, 10 vesicle stability of, 12-14

Fluorescence resonance energy transfer (FRET) technique, 109

Fluorescence spectroscopy, 223-225

Fluorophores, 223-224 Folate-PEG-coated vectors, 190 Fourier-transformed infrared

spectroscopy (FTIR), 272 Freeze-dried rehydration vesicles, 216 Freeze drier (FD-1), 37 Freeze drying, 35 of monophase solutions, 35 from TBA/water cosolvent

systems, 36 technique. See Lyophilization

Freeze-etching apparatus, 23 Freeze-fracture electron microscopy

(FFEM) egg phosphatidylcholine

vesicles, 61 egg PC multilamellar liposome, 60 in mixed lipid-detergent systems, 210 self-closing bilayered fragments

analysis by, 217 vesicle lamellarity, 60

Freeze-fracture transmission electron microscopy of VPGs, 245-246

Fusogenic liposomes, 140

Gamma-ray-perturbed angular correlation spectroscopy technique, 301

Gas chromatography method, 44

Gemcitabine, 248, 255 VPG and, 254 dilution of, 255 intratumoral (IT) application of,

255 intravenous (IV) application

of, 255-257 preparation and in vitro

characterization of, 254-255 stability of, 255

GemConv, 255 maximum tolerated dose (MTD)

for, 256 GemLip, 255 area under the curve (AUC) for, 256 maximum tolerated dose (MTD)

for, 256 PK-study of, 256

Gendicine. See Gene therapy Gene therapy clinical trials, 98-99 vectors used in, 99

history of, 97-98 liposome-DNA complexes

used in, 99 Gene transfer system, 98 Gibbs phase rule, 9 Glutathione (GSH), 177, 182 Glycosidic bond hydrolysis of, 270 nonenzymatic browning and stability

of, 269 Good manufacturing practices (GMP) pDNA manufacture, 101 viral transfection systems, 99

Gouy-Chapman-Stern nonlinear approximation model, 289

Green fluorescent protein (GFP), transfection of, 148-149, 186

Hemagglutinin (HA) influenza, 86, 91 polypeptides of, 86 role in virosomes, 86 virosomal fusion activity by, 94

Hepatitis A viruses (HAV), 93

High performance liquid chromatography, 114, 286

High pressure homogenization vesicles, 216

Host-plasmid combination, 101 HPLC. See High performance liquid

chromatography Hudson jet nebulizer, 72 Human aorta endothelium cells

(HAEC), 106 Human bladder cancer BXF 1299T, 255 Human leukocyte antigen (HLA)-A2

transgenic mice, 91 Human smooth muscle cells

(HASMC), 106 Human soft tissue sarcoma SXF 1301,

255 Humoral immune response induction of, 87-90 of virosomes, 87

Hydrazone, 168 Hydrofluoroalkanes (HFAs), 69 Hydrolysis, amine-influenced, 289 Hydrophilic drugs in oil solubilization of, 43 drugs used, 45 experiment in, 43-46 factors affecting, 47-48 formulations, 44 materials used for, 43-44 mechanism of, 48-49 studies on, 44

Hydrophilic polyacrylamide backbone, 199

Hydrophilic spacer, 200 Hydrophobic bile salt, 221 transfer enthalpy of, 222

Hydrophobic ion-paired complexes, 43 Hydrophobic-lipophilic balance of

polymers, 198 Hydrophobic pendant groups, 197, 199

Iatroscan MK-5, 22 Influenza, 86 Insulin, 44 absorption in diabetic rats, 45, 51

[Insulin] analysis of, 45 hypoglycemic effect, 45, 50-51 Wistar rats, 45

in nondiabetic rabbits, 45 solubilization of hydrophilic

drugs, 44 Interferon c (IFNc) release, 91 Isothermal titration calorimetry (ITC),

112-113, 210 critical aggregation/micelle

concentration, 214 derivation of aggregation number, 216 detergent dilution experiment,

212-213 detergent partitioning into vesicles,

217-223 protocol, 221 in thermodynamics of micelle

formation, 211 Isothiuronium-masked cationic

detergent, 179 critical micelle concentration of, 182

Isothiuroniumdetergent 45, 185

Jet nebulizers aerosol output from, 69 conventional liposome delivery, 72

Ketal and pH-sensitive mPEG-lipid

conjugates, 168 and pH-sensitive surfactants, 168 linkage, 167-168

Ketal linkage, pH-sensitive, 167 Konakion1 MM, 234 Kuchinka and Seelig approach, 219

Lactate dehydrogenase (LDH), 71 nebulization, 77 protein, 75

Lamellar fatty acid/soap bilayers, 10 Lamellar fatty acid/soap phase, 1 Lamellar liquid crystalline phase, 5

Lamellarity definition of, 28 of lipid vesicles, 28

Large unilamellar vesicles (LUVs), 10, 38

extrusion and, 55-56 LDH. See Lactate dehydrogenase LipexTM extruder, 57 Lipid(s) binary mixture of, 272-274 phase separated domains in, 274 reducible and nonreducible, 186 transfection efficiency of, 184

Lipid-DNA complexes binding affinity, 114 DC-30 with, 106

Lipid/DNA charge ratio, effect of, 144-145, 147

formation of, 105-108 optimal ratio of, 106 reproducible method of, 108

Lipids, pH-responsive chemistry of, 167-170

Liposomes, pH-responsive for gene delivery, 175-177 hydrolysis of, 170-175

Lipids, pH-sensitive, 167, 169 Liposomes, pH-sensitive, 165-166 Lipids, reduction-sensitive, 179 Lipid-to-plasmid ratio, 106 Lipid vesicles characteristics of, 28 coacervation technique in, 22-24 formation of, 217 freeze-fracture electron micrographs

of, 29-30 particle sizes, 24 effect of added water, 28-29

preparation of, 23, 216 size and lamellarity control, 29 suspension, 23

Lipoic acid-derived cationic amphiphiles, 179-180

Lipoic acid-derived lipids, transfection activity of, 185

Lipoic acid for nonviral gene delivery, 185

Lipoplexes acid-labile formulations, 139 acid-sensitive, 142 aggregation of, 116 analytics, 113-114 atomic force microscopy (AFM)

in, 109 binding of, 112 biophysical characterization

of, 108-113 cryo-TEM images by DAC30

of, 109 dispersion, 108 DNA accessibility, 114 effect of size in, 116-118 electron microscopic techniques, 109 homogeneity determination of, 113 in vitro tests of, 118 infrared spectroscopy and circular

dichroism in, 113 long-term stability of, 117-118 lyophilization of, 114-117 parameters for transfection and

stability of, 108 photon correlation spectroscopy

in, 113 physicochemical characteristics

of, 118 size and biological activity of, 119 structural properties of, 112 transfection activity of, 176 transfection efficiency of, 118-121 X-ray and neutron scattering methods

in, 111-113 Liposomal amikacin, 301 Liposomal amphotericin B product, 306 liposomal amphotericin B product,

concentration (K50) of, 308 Liposomal dispersions, 297 Liposomal doxorubicin (DOX)

product, 301 Liposomal formulation, 299 Liposomal products, 42 Liposomal therapeutics injectable, 298 process development and quality

control of, 297

Liposome(s) airway delivery, 68 autoclaving of, 291-292 bilayer constituents of, 285 bioresponsive, 165 multifunctional, 189-191

conventional, 301 cryoprotectants in, 68 deposited on aerosols, 72 dispersions, 101 size distribution for, 301-303

DNA complexes, 99 1,2-dioleoyl-sn-glycero-3-phospha-

tidylethanolamine (DOPE), 168

drug delivery, advantages of, 67, 139 products, definition, 122

in dry state, 263, 265 enzymatic destabilization, 270-272

eggPC, 72 elastase-responsive, 187 enzymatic activity, 272 enzymatic destabilization of, 270-272 enzyme-responsive, 186-188 Evans’ method, 42 extrusion, 61 ethanol in, 63-64

formation, 39, 100-101 carrier/lipid ratio in, 39 characterization assays for, 101-102 by extrusion technique, 100 lipid composition in, 39 mechanism, 39-41 preparation methods, 100 sterilization procedure of, 101 sucrose in, 41 types of carriers in, 39

formulation of, 68, 299 freeze drying of, 68, 69 effect of trehalose on, 78-79 preparation of, 71

fusogenic, 140 gels. See Vesicular phospholipid gels glass transitions and stability of,

267-268 instability, problems of, 68 lipid composition of, 266

[Liposome(s)] loading, 41, 285 multilamellar and reverse-phase

evaporation, 70 nebulizing, 72, 74 non-freeze-dried, 78 PEG-coated, 287 phase diagram, 23 phase separation of, 272, 276 pH-responsive, 166-177 preparation of, 21, 23, 70-71 alcohol and, 24-27 coacervation method, 22-24 emulsification process, 22 ethanol and, 28 filters used in, 57-58 lamellarity of, 58-59 phosphatides in, 22

protectants used in, 114-115 pyrogen-free submicron, 36 recycling of, 73 reduction-responsive, 177-186 size measurements, 37 Coulter counter or photon

correlation, 71 Fraunhofer diffraction analysis, 71

spray-dried, 69 stability, 285 stabilization of, 261 arbutin in, 266 mechanism for, 265 requirements for, 263

state diagram in, 267-268 sterilization, 291 by autoclaving, 291-292 by gamma irradiation, 292

stress and consequences in, 298-299

structure of, 28-30 by TBA/water cosolvent systems,

36-37 therapeutic index enhancement

of, 299 thermal analysis and x-ray diffraction

of, 37 triggering mechanisms of, 186-187 unilamellar, 100

[Liposome(s)] See also Vesicular self-assemblies

Liposomes reduction-responsive chemistry of, 178-181 for gene delivery, 184-186 properties, 181, 183-184

Lipopolyamines Reductionsensitive, 182

Listeriolysin O (LLO), 188 Luciferase (Luc) reporter gene,

143, 153 Luciferase plasmid DNA, 188 Lyophilization, 35 of lipoplexes, 114-117 See also Freeze drying

Lyoprotectants, 115

Maillard (browning) reaction, 269 Major histocompatibility complex

(MHC) class, 87 Malachite green fixation technique, 23 Malarial parasite, 89 Mass median aerodynamic diameter

(MMAD), 78 Mass spectrometry, in quantifying

phospholipids, 286-287 Micellar solubilization, 224 Micelle(s) critical micelle concentration

(CMC), 211 formation and hydrophobic effect,

210-211 mechanisms, 210-216 thermodynamics, 211

Microencapsulation vesicle (MCV) method, 21

advantages of, 21-22 MiKasome, 301. See also Liposomal

amikacin Mixed lipid-detergent systems formation of, 217 Gibbs phase rule in, 221 Gouy-Chapman theory in, 220 Graham equation in, 219

intermediate structures of, 209 Mixed micelles (MMs), 209, 217

[Mixed micelles (MMs)] for contrast agents development, 234 formation of, 210-216 pharmaceutical aspects of,

233-234 physicochemical characterization of,

223 thermodynamic stability and phase

diagrams of, 229-233 Mixed vesicles (MVs), 209, 216 formation of, 216-217 Gibbs phase rule in, 211 pharmaceutical aspects of,

233-234 phase diagrams of, 229-233 physicochemical characterization

of, 223 Mixed vesicles and mixed micelles

fluorescence spectroscopy, 223-225

formation mechanisms of, 210-217 pharmaceutical aspects of, 233-234 phase diagrams of, 229-233 photon correlation spectroscopy,

225-227 small angle scattering techniques

for, 227-229 physicochemical characterization of transitions of, 223, 229

Multifunctional bioresponsive liposomes, 189-191

formation of, 189 gene transfer by, 189 sequential assembly of, 189-191 transfection activity of, 189

Multilamellar liposomes (MLVs), 38 conversion to SUV, 43 egg phosphatidylcholine, 59 extrusion of, 56, 62 freeze-thaw cycles, 59-60 preparation, 70-71

Multiple-antigen peptide (MAP), 89 Multistage liquid impinger (MSLI),

aerosols produced from, 72 Multivesicular vesicles

(MVVs), 248-249 Myocet1, 42

Nanolipoparticles (NLPs), 177 pH-responsive, 177 POD, 177 TAT-PEG-lipid on, 191 transfection activity of, 177

Nebulization, 72 effect of jet, 75-76 of EggPC/Chol liposomes, 77 LDH activity and, 77 of proliposomes, 79-82 of rehydrated freeze-dried

liposomes, 78 salbutamol sulphate and, 81-82

Nebulizers aerosol output from, 69 cirrus, 73 droplet size selectivity by, 74 jet, 69-70 phospholipid distribution in, 80-81 Respirgard II1, 73 sidestream, 73 ultrasonic, 69-70 vibrating mesh, 70

Neuraminidase (NA), 86 N-methoxysuccinylanlanyl

alanylprolylvalyl-DOPE (MeO-suc-AAPV-DOPE), 187

N-Palmitoyl homocysteine, 140 Nonviral transfection systems, 98-100 Normalized quantitative turbidity

(NQT) technique, 305 NucleporeTM brand membranes, 58 Nuclepore filter, 62

Octanoic acid, 5 Octylglucoside, 217 Oil-based thymopentin

formulation, 50 Oleic acid/sodium oleate, titration

curve, 7-10 Oleic acid vesicles, 2 application of, 16

Oligonucleotides (ODNs), 177 Orthoester cyclic, 175 lipids, 172

[Orthoester] surfactant, 169 synthon, 6, 142, 150

Orthoester-based pH-labile lipid degradation of, 156 tricyclic linker by, 156

Palmitoyl glycol chitosan amphiphiles, 202

Palmitoyl oleoyl phospatidylcholine (POPC), 221-222

phase diagrams for solubilization of, 231-232

p-Toluene sulfonic acid (PTSA) catalysis, 142, 150

in refluxing toluene, 150 Parasite, malarial, 89 Pari Master compressor, 70 pDNA. See Plasmid DNA PEG. See Polyethyleneglycol Pegylated liposomes. See Polyethylene

glycol (PEG) derivatized lipids Peptide epitope-specific immune

response, 89 Peptide protamine (PN), 188 Pharmaceutical guidelines and

regulations, 121 internet addresses for, 123

Phase diagram of coacervate system and effect of

alcohols, 24-27 fatty acid-soap-water

systems, 3 of phospholipid-methanol-water

system, 24-25 of phospholipids-ethanol-water

system, 25-26 of potassium oleate-oleic

acid-water, 5 of 1-propanol-phospholipid-water,

25-26 of 2-propanol-phospholipid-water

systems, 25, 27 of sodium octanoate-octanoic

acid-water, 3-4 Phase separation and domain structure,

Phosphatides analysis of, 22 phospholipid compositions of, 22 refined egg yolk, 22

Phosphatidylcholine (PC), 140, 289, 301

hydrolysis rate of, 288 Phosphatidylglycerol, 289 Phospholipase A2, 188, 271-272 Phospholipase C, 188 Phospholipids (PLs) chemical degradation of, 287 coacervate system of, 24 column materials separation of, 286 detergent mixtures, 221 enzymatic assays for quantifying, 287 HPLC separation of, 286 vesicles formation, 242

hydrolysis of, 285, 287-291 lamellar phases formation, 242

in liposomes, 285 mass spectrometry in

quantifying, 286 quantifying techniques, 286-287 solubility characteristics of, 38 stability monitoring by ELSD, 286 systems, partition coefficients

of, 221-222 triangular diagram of, 24-27 vesicles, 241

Phospholipid-alcohol solutions, 23 Phospholipid-ethanol-water system aggregation, 24-26 coacervation field , 24-26 ternary phase diagram of, 24-26 viscous gel phase, 24-26

Phospholipid-methanol-water system coacervation field, 24 ternary phase diagram of, 24-25 viscous gel phase, 24

Phospholipid-2-propanol-water system, 25

coacervation field, 26-27 ternary phase diagrams of, 26-27 viscous gel phase, 26-27

Phospholipid-water-alcohol systems, 22

Photon correlation spectroscopy (PCS), 113, 223, 225-227, 249

Plasmid, 101 covalently closed circular (CCC),

101, 105 fermentation titer of, 104 open circular (OC), 104-105 production by Escherichia coli,

102-103 stability and quality control, 105 topologies, 101, 104

Plasmid DNA (pDNA) agarose gel electrophoresis, 105 chromatography of, 105 complexed, 101 fermentation of, 101-104 homogeneity of, 101, 103 manufacture of, batch processes, 103

Escherichia coli host strain for, 101

plasmid production in, 102 purification process in, 104-105 quality of, 101, 103 quality control tests and assays,

105-106 impurities extraction, 101 topomers, 103

Plasmodium falciparum, 89. See also Malarial parasite

31P-Nuclear magnetic resonance (31P-NMR), 59

Poly (ethylene glycol) monomethyl ether (mPEG), 167

chain length, 169, 174 Poly (ethylene glycol) monomethyl

ether-diortho ester-lipid conjugate (POD), 169

acid sensitivity of, 174 DOPE liposomes, 174 features of, 175 for gene therapy, 177 gene transfer activity of, 176-177 mPEG chain length, dependence on,

169, 174 nanolipoparticles (NLPs), 177 PE liposomes, 174 synthesis of, 169

Polyethylene glycol lipids pHdegradable

Polyethylene glycol (PEG) lipids pHlabile, 149-150

aggregation kinetic of lipoplexes with, 151

degradation studies of, 150-152 hydrolysis rate of, 150-152 in vitro tests in, 153-155 orthoester linkers, 158 physicochemistry of, 153 preparation from chol PEG, 151 synthesis of, 150

Poly (l-lysine) vesicle system, 202 biological activity of, 205 in gene delivery, 203 polyamine, 200

Polyethyleneglycol (PEG), 301 hydrolysis of PEG, 287 polyamino acid, 200

Polyethyleneglycol-lipid conjugates, 289

Polyethylenimine polymers bilayer arrangement of, 201 biological activity of, 205 in gene delivery, 203

Polymer 1, 197-198 Polymer 2, 199 Polymer 3 (chitosan), 200 Polymer 4 (polyamine), 200 Polymer 5 (polyamine), 200 Polymer 6 (polyamino acid), 200 Polymeric vesicles, 197 carbohydrate, 205-206 drug delivery by, 203-206 enzyme-activated, 205-206 fabrication of, 203 gene delivery systems in, 203 molecular weight parameter in preparation, 202-203

stability of, 199 unilamellarity of, 199

Polysorbate 80, 44 Potassium oleate-oleic acid-water, 5 CMC for, 5 phases of, 5-6 ternary phase diagram for, 5

Pressurized metered dose inhalers (pMDIs), 69

Proliposomes alcohol-based, 68, 71 nebulization of, 79-82 particulate-based, 68, 71

Protocell model, by fatty acid vesicles, 15-16

2,20-Pyridyl disulfide, 178, 181

Rafts. See Phase separated domains, 276 Rat pharmacokinetics of conventional PC:chol and PEG

PC:chol, 300 of Doxil, 301-302 of MiKasome, 301-302 of VesCan, 300

Reporter fluorophore, 223 Respirgard II1 nebulizer, 73 Reticuloendothelial system (RES)

clearance, 298 Reverse-phase evaporation

methods, 56 Reverse-phase evaporation vesicles

(REVs), 71, 216 Rotational viscometer, 246

Salbutamol sulphate (albuterol sulphate), 71

Sarcoplasmic reticulum (SR) membranes, 263

Scanning electron micrographs (SEM) of lipid vesicles, 24, 30-31 by Malachite green fixation

technique, 23 surface topography of lipid vesicles

by, 30 Sephadex G-50 gel, 248 Severe combined immunodeficiency

syndrome (SCID), 98 Size-exclusion chromatography (SEC),

248 SKnSH cells, 185 Small angle neutron scattering (SANS),

223, 227-229

Small angle X-ray scattering (SAXS), 223, 227-229

Small unilamellar vesicles (SUVs), 43, 241

dispersion, 248, 304 interaction of, 298 liposome structure, 298

Sodium cholate (NaC), 221-222 aggregation number of, 216 See also Hydrophobic bile salt

Sodium cromoglicate (cromolyn sodium), 71

Sodium deoxycholate (NaDC), 216, 222

for dissolution of fat, 234 See also Hydrophobic bile salt

Sodium dodecylbenzenesulfonate (SDBS), 13

Sodium dodecylsulphate (SDS) solution, 212

Sodium octanoate-octanoic acid-water, 3

CMC for, 4 isotropic liquid phases of, 4-5 lamellar liquid crystalline phase of, 5 phase diagram of, 4-5 ternary phase diagrams for, 3-5

Solvent hydrophilicity and phospholipid-alcohol-water ratio, 29

Sonicated small (unilamellar) vesicles [S(U)Vs], 216

Soybean phosphatidylcholine (SBPC), 221-222

phase diagrams for solubilization of, 231-232

Soybean phosphatidylcholine (SPC), 37 as masking agent, 44-45, 47-48

Soybean phosphatidylglycerol (SPG), 37

Soybean phosphatidylserine (SPS), 37 Spermine, 142 Spherical mixed micelles (SMMs), 209 Sphingomyelinase, 188 Stabilized plasmid-lipid nanoparticles

(SPLP) pH-insensitive, 177

[Stabilized plasmid-lipid nanoparticles (SPLP)]

POD, 176 Streptavidin, 88 Sucrose, in liposome formation, 40 Surfactants pH-sensitive, 167-168 ketal based, 168

T helper epitopes, 90-91 Tertiary butyl alcohol (TBA), 35, 40 measurement of, 44 phase diagram of, 38

water cosolvent systems, 35 and freeze drying, 36

water-volume ratio, 39 Tethering molecules, 178-179 Thermogravimetric analysis (TGA), 44 Thin-layer chromatography with

flame-ionization detection (TLCFID), 22

Thiocholesterol-based cationic lipids (TCL), 181

comparison of transfection activity of, 185

lipoplexes, 184 Thiol cationic detergents, 179, 181 critical micelle concentration

of, 182 Thymopentin (TP5), 44 Trans-orthoesterification, 141 Trehalose, 268 and biostability, 262 browning in, 269-270 during storage, 270-271 dry eye syndrome, 262 glycosidic bonds linking in, 267 liposomes, freeze-dried without, 78 phase separation, 275-276 properties of, 267

TritonTM X-100, 224, 227 Two-stage (twin) impinger (TI), 72 liposomes deposited in, 78-79

Unilamellar and oligolamellar vesicles (LUVs, OLVs), 216

Vaccines synthetic peptide-based, 91 Valium1 MM, 234 Vectors adenovirus, 98 BGTC, 156 viral, 189

VesCan injection of, 301 in vivo tumor diagnostic agent, 301

Vesicle(s) formation cholesterol in, 202 detergent depletion method

in, 216-217 hydrophilic spacer in, 200 mechanism of, 216-217

glycol chitosan, 205 hydrodynamic diameter, 202 polymeric, 197-199 preparation, 202-203

Vesicle-micelle transition, 2 Vesicular phospholipid gels (VPGs) ball-mill dispersion of, 249-251 carboxyfluorescein and, 252

characteristics of, 241, 245-246 sustained drug release,

246, 248 concept of, 257 definition, 241 calcein diffusion, 248 diluted, 249 drug entrapment

in, 243-244, 245 drug loading, 243-244 empty (drug-free), 244 encapsulation efficiency of,

251-252 freeze-fracture transmission electron

microscopy of, 245-246 Gemcitabine-containing, 254 liposomal preparation of, 254

[Vesicular phospholipid gels (VPGs)] liposomes dispersions of, 250 PCS analysis, 249 pharmaceutical applications of, 254 preparation of, 243 size electronmicroscopic analysis,

249, 251 sterilization of, 245 SUV dispersions, 248-249

Vesicular self-assemblies, 197, 199-202

hydrophilic spacer for, 200 polymer-specific factors impacting,

198 Vibrating-mesh nebulizer, 79 Vincristine, 248 Viral transfection systems, 98-99,100 Viral vectors, 189 Viral versus nonviral transfection

systems, 99-100 Virosomal hepatitis A vaccine. See

Epaxal Virosomes action of, 87 adjuvant capabilities of, 85 antigen delivery by, 85, 89-90 and antigen processing, 88 antimalaria peptide epitopes, 89 based vaccines, 85, 91-93 as carrier, 89-90 CD8T cell response to, 90 characteristics of, 86 cytokines and, 85 for drug delivery, 94 effect of, adjuvant, 88 immune response to, 87-89 glycoprotein and, 86 hemagglutinin, 86 synthetic peptide vaccine, 89 T cell response by, 91

Virus, artificial. See Artificial virus