Drug Targeting Organ-Specific Strategies

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3.9 Inspiratory Pressure and Relevant Flow Parameters 75 where Φ V is the volumetric flow rate, ρ A is the density of the air (upstream of the flow constriction) and Fu(A) is a function of the cross-section of the flow constriction. Several authors use a simplification of this formula, written in terms of driving force (√∆P), airflow resistance (R E) and volumetric airflow (Φ V) (e.g. references [22,100]). √∆P = R E x Φ V (3.2a) In this equation, R E is the reciprocal of Fu(A) x √(2/ρ A). If there is no interaction between the flow through the inhaler and the flow in the respiratory tract, total resistance (R TOT) may be written as R TOT 2 = RI 2 + RE 2 . It has been reported that a high external resistance influences the shape and width of the human pharynx and larynx in a manner favourable for deep lung deposition [101]. The resistance of dry powder inhalers can be calculated by measuring the volumetric flow rate and the pressure drop across the device simultaneously and applying Eq. 3.2a for the calculation. Values for some marketed DPIs are given in Table 3.7, showing that there are remarkable differences between devices. Table 3.7. Airflow resistances of some marketed dry powder inhalers in kPa 0.5 min l –1 . Reference [100] [144] [145] Mean Glaxo Rotahaler 0.013 0.013 0.014 0.0133 Fisons Spinhaler 0.016 0.015 0.015 0.0153 Pharbita Cyclohalera 0.017 0.018 0.018 0.0177 Sofotec Novolizer – – 0.026 0.0260 Glaxo Diskhalerc 0.021 0.018 0.030 0.0230 Glaxo Diskus – – 0.032 0.0320 Astra Turbuhaler 0.031 0.039 0.040 0.0367 Inhalator Ingelheimb 0.056 0.053 0.048–0.058 0.0540 Chiesi Inhaler – 0.093 – 0.0930 a Also known as ISF inhaler and Novartis (Foradil) Inhaler. b The range in reference [145] is a consequence of poor reproducibility in capsule piercing. c The spread for the Glaxo Diskhaler may come from the use of two different devices: four-dose [145] and eight-dose [100, 144]. 1 technical bar equals 1000 mbar = 105 Pa (N m-2 or kg s-2 m-1 ) = 102 kPa Resistances have been (re-)calculated for standard liters per minute (at 20 °C: LS min-1 = 1,0733*LN min –1 ). 3.9 Inspiratory Pressure and Relevant Flow Parameters Several authors measured attainable pressure drops as a function of the external resistance for different groups of volunteers. Healthy male subjects (during maximal inspiration) are able to create a pressure drop (on average) of 6.7 kPa through an airflow resistance of 0.038 kPa 0.5 min l –1 , (which is in the range of that of marketed DPIs, see Table 3.7), whereas females are able to create a pressure drop of 3.8 kPa under the same resistance [22]. Differences between different groups of patients depend on the degree to which pulmonary func-
76 3 Pulmonary <strong>Drug</strong> Delivery: Delivery To and Through the Lung Figure 3.5. The effect of external resistance and clinical conditions on the pressure drop generated at maximum inhalation effort. The area between the dashed lines represents the 95% confidence interval.
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Drug Targeting Organ-Specific Strat
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Preface Drug Targeting Organ-Specif
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Foreword Drug Targeting Organ-Speci
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X List of Contributors Henderik W.
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XII List of Contributors Grietje Mo
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Contents Drug Targeting Organ-Speci
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Contents XVII 3 Pulmonary Drug Deli
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Contents XIX 5.2.1.6 Identification
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Contents XXI 7.5 In Vitro Technique
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Contents XXIII 9.4 Tumour Vasculatu
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Contents XXV 12.8. Tissue Slices fr
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Dexa dexamethasone DIVEMA divinyl e
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LRP lung resistance related protein
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ROS reactive oxygen species RSV res
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Index a ADEPT 217, 224, 268, 291 ad
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e E. coli expression system 292 eff
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polymers, soluble 4, 218 - dendrime
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2 1 Drug Targeting: Basic Concepts
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Page 61 and 62: 24 2 Brain-Specific Drug Targeting
Page 91 and 92: 54 3 Pulmonary Drug Delivery: Deliv
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Page 125 and 126: 4 Cell Specific Delivery of Anti-In
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Page 129 and 130: 4.2.2.2 Phagocytosis and Transcytos
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Page 133 and 134: 4.3 Hepatic Inflammation and Fibros
Page 135 and 136: process is not yet available. Sever
Page 137 and 138: this carrier to the KCs.When the ma
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Page 141 and 142: y the transcriptional regulatory pr
Page 143 and 144: 4.8 Testing Liver Targeting Prepara
Page 145 and 146: 4.8 Testing Liver Targeting Prepara
Page 147 and 148: 4.9 Targeting of Anti-inflammatory
Page 149 and 150: 4.9 Targeting of Anti-inflammatory
Page 151 and 152: with monoclonal and bispecific anti
Page 153 and 154: References 117 [50] Coleman DL, Eur
Page 155 and 156: References 119 [133] Cronstein BN,
Page 157 and 158: 5 Delivery of Drugs and Antisense O
Page 159 and 160: 5.1 Introduction 123 convoluted tub
Page 161 and 162: treatment of the targeted cell and
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CL uptake (ml/min/g) centration pro
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5.2.1.4 Specific Binding of Alkylgl
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5.2 Renal Delivery Using Pro-Drugs
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5.2 Renal Delivery Using Pro-Drugs
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5.3 Renal Delivery Using Macromolec
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5.4 Renal Delivary of Antisense Oli
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5.4 Renal Delivery of Antisense Oli
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5.4.8 Benefits and Limitations of A
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via reabsorption from the luminal s
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References 153 [66] Franssen EJF, M
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References 155 [145] Van Zwieten PA
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158 6 A Practical Approach in the D
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172 7 Vascular Endothelium in Infla
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8 Strategies for Specific Drug Targ
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8.2.2 Histogenesis The traditional
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may become obstructed and compresse
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8.5 Strategies to Deliver Drugs to
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8.5 Strategies to Deliver Drugs to
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larly cytotoxic immune effector cel
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contributes to limited tumour penet
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ples onto anti-EGP-2 scFv. Biologic
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In the case of drug-monoclonal anti
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cells, the presence of co-stimulato
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Monomethoxy-polyethylene glycol CH
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e efficiently loaded into the lipos
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8.6 Clinical Studies 223 Table 8.5.
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8.6.3 (Synthetic) (co)Polymers Solu
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8.8 Conclusions and Future Perspect
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References 229 [43] Chaouchi NA, Va
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References 231 [126] Czuczman MS, G
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234 9 Tumour Vasculature Targeting
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256 10 Phage Display Technology for
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11 Development of Proteinaceous Dru
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carrier is an homogenous product. I
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11.3 The Homing Device 11.3 The Hom
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malian cell lines that have acquire
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jugates for the delivery of other a
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11.5 The Linkage Between Drug and C
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actions are directed towards these
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11.5 The Linkage Between Drug and C
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homing potential if the antigen rec
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ly used promoters include T7 RNA po
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the baculovirus expression vector,
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11.8 Recombinant DNA Constructs 297
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11.8 Recombinant DNA Constructs 299
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toxic activity. Anthrax and tetanus
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11.9 Recombinant Domains as Buildin
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References 305 [16] Milstein C, Wal
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References 307 [99] Verma R, Boleti
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12 Use of Human Tissue Slices in Dr
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are also extensively used in a vari
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Meanwhile many incubation systems h
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12.3 Incubation and Culture of Live
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to investigate the effect of differ
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The mechanisms of uptake and excret
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12.6 The Use of Liver Slices in Dru
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12.7 Efficacy Testing of the Drug T
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NO x µM 80 60 40 20 * * 12.7 Effic
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TNFα ng/ml 1.5 1 0.5 0 * Human (n=
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References 329 [33] Ikejima K, Enom
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References 331 [109] Dutt A, Priebe
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334 13 Pharmacokinetic/Pharmacodyna
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372 14 Drug Targeting Strategy: Scr
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374 14 Drug Targeting Strategy: Scr
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Drug Targeting Organ-Specific Strategies

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