- •Drug Product Development for the Back of the Eye
- •Preface
- •Contents
- •Contributors
- •1.1 Introduction
- •1.2 A Strategic Overview of Drug Delivery Systems
- •1.3 Specific Approaches to Drug Delivery for the Posterior Segment
- •1.3.1 The Influence of Physicochemical Properties on Drug Delivery and Pharmacokinetics
- •1.3.2 The Chosen Route of Administration
- •1.3.3 Location of the Target Tissue
- •1.3.4 Potency of the Drug
- •1.3.5 Need for Continuous or Pulsatile Delivery
- •1.3.6 Duration of Drug Delivery Necessary to Induce and Maintain Efficacy
- •1.3.7 Type of Drug Delivery System Selected
- •1.3.8 Pharmacokinetic (PK) Properties of the Drug
- •1.3.9 Local and Systemic Toxicity of the Drug and its Metabolites
- •1.3.10 Previous Ocular Use of Excipients
- •1.3.11 Development and Strategic Team Input
- •References
- •2.1 Introduction
- •2.2 Posterior Segment as a Sampling Site
- •2.3 Principle of Microdialysis
- •2.3.1 Extraction Efficiency/Recovery
- •2.4.1 Anesthetized Animal Models
- •2.4.2 Conscious Animal Model
- •2.5 Vitreal Pharmacokinetics in Animals Other than Rabbits
- •2.6 Summary
- •References
- •3.1 Commercial Fluorophotometer
- •3.2 Normal Human Subject and Rabbit Ocular Fluorescence
- •3.3 Fluorophotometry Applications
- •3.3.1 Tear Turnover Rate (%/min)
- •3.3.2 Corneal Epithelial Cell Layer Permeability Methodologies
- •3.3.3 Eye Bath Technique
- •3.3.4 Single Drop Technique to Measure Epithelial Permeability
- •3.3.5 Eye Bath Technique to Measure Epithelial Permeability
- •3.4 Clinical Applications of Fluorophotometry
- •3.5.1 Transscleral Pathways
- •3.5.2 Suprachoroidal Injection
- •3.6 Retrobulbar Fluorescein Injection
- •3.7 Intravenous Fluorescein Injection In Vivo
- •3.8 Ocular Uptake of Fluorescein from Topical Eye Drops
- •References
- •4.1 Introduction
- •4.1.1 Role of the Blood-Retinal Barrier as a Dynamic Interface
- •4.1.2 Potential Approach of Blood-Retinal Barrier-Targeted Systemic Drug Delivery to the Retina
- •4.2.1 Amino Acid-Mimetic Drugs
- •4.2.2 Monocarboxylic Drugs
- •4.2.3 Nucleoside Analogs
- •4.2.4 Folate Analogs
- •4.2.5 Organic Cationic Drugs
- •4.2.6 Opioid Peptides and Peptidomimetic Drugs
- •4.2.7 Antioxidants
- •4.2.7.1 Vitamin C
- •4.2.7.2 Vitamin E
- •4.2.7.3 Cystine
- •4.2.8 Miscellaneous Protective Compounds
- •4.2.8.1 Creatine
- •4.2.8.2 Taurine
- •4.3.1 Organic Anion Transporter 3 (OAT3, SLC22A8)
- •4.3.3 P-Glycoprotein (ABCB1)
- •4.3.4 Multidrug Resistance-Associated Proteins (ABCCs)
- •4.3.6 ABCAs
- •4.4 Conclusions and Perspectives
- •References
- •5.1 Introduction
- •5.2 Drug Distribution
- •5.2.1 Drug Distribution from the Anterior Ocular Surface to the Posterior Segment
- •5.2.2 Studies of Trans-Corneal and Periocular Drug Delivery to the Retina
- •5.2.2.1 The Uvea-Scleral Route
- •5.3 Eye Drops for Posterior Segment Diseases in the Clinic
- •5.4 Summary
- •References
- •6.1 Introduction
- •6.2 Vitreous Anatomy
- •6.2.1 The Inner Limiting Membrane
- •6.3 The Vitreous As a Drug Reservoir
- •6.4 Flow Processes in the Vitreous
- •6.4.1 Flow Patterns
- •6.4.2 Injection and Hydrostatic Effects
- •6.4.3 Diffusion
- •6.4.4 Convective Flow
- •6.5 Clearance Pathways from the Vitreous Compartment
- •6.5.1 Charge and Collagen Interaction
- •6.5.2 Aqueous Clearance
- •6.5.3 Retinal Clearance
- •6.6 Transfer Through the Vitreoretinal Border
- •6.6.1 The Role of the Blood–Retinal Barrier
- •6.6.1.1 Amino Acid Transport
- •6.6.1.2 P-Glycoprotein
- •6.6.1.3 Organic Cationic Transporters
- •6.6.1.4 Organic Anion Transporters
- •6.6.1.5 Other Transporters
- •6.7 The Ageing Vitreous
- •6.7.1 Underlying Mechanisms of Vitreous Degeneration
- •6.7.2 Physical Changes Involved in the Ageing Vitreous
- •6.7.2.1 Pre-Clinical Model of Ageing Vitreous
- •6.7.2.2 Effects of Vitreous Liquefaction on Intravitreal Drug Delivery
- •6.7.3 Vitrectomised Eyes
- •6.7.3.1 Intravitreal Drug Distribution and Clearance in Silicone Oil
- •6.7.4 Role of Ocular Movements in Disordered Vitreous
- •6.8 Concluding Remarks
- •References
- •7.1 Introduction
- •7.2 Drug Delivery to Posterior Segment Ocular Tissues
- •7.3 Scleral Structure and Drug Delivery
- •7.4 Scleral Permeability: Initial Studies
- •7.5 Sustained-Release Delivery In Vitro
- •7.6 In Vivo Studies
- •7.7 Conclusions and Future Directions
- •References
- •8.1 Introduction
- •8.2 Background
- •8.3 Posterior Segment Delivery
- •8.4 Transscleral and Intrascleral Drug Delivery
- •8.5 Suprachoroidal Drug Delivery
- •8.6 Summary
- •References
- •9.1 Introduction
- •9.2 Nonbiodegradable Ocular Drug Delivery Systems
- •9.2.1 Retisert
- •9.2.2 Ocusert
- •9.2.3 Vitrasert
- •9.2.4 I-vation
- •9.2.5 Iluvien
- •9.2.6 Nonbiodegradable Matrix Implants
- •9.2.6.2 Punctal Plugs
- •9.3 Medical Applications for Biodegradable Polymers
- •9.3.3 Poly(Ortho Esters)
- •9.3.4 Polyanhydrides
- •9.5.1 Ozurdex™
- •9.5.2 Surodex
- •9.5.3 Verisome
- •9.5.4 Lacrisert
- •9.6.1 Poly(Lactic Acid)-Based Implants
- •9.6.2 PLGA-Based Implants
- •9.6.5 Poly(Ortho Ester)-Based Implants
- •9.6.6 Polyanhydride-Based Implants
- •9.6.7 Other Biodegradable Polymer-Based Implants
- •9.7 Conclusions
- •References
- •10.1 Introduction
- •10.2 Manufacturing of Microparticles
- •10.3 Characterization of Microparticles
- •10.3.1 Morphological Characterization of Microparticles
- •10.3.2 Particle Size Analysis and Distribution
- •10.3.3 Infrared Absorption Spectrophotometry (IR)
- •10.3.4 Differential Scanning Calorimetry (DSC)
- •10.3.5 X-Ray Diffraction
- •10.3.6 Gel Permeation Chromatography (GPC)
- •10.3.7 Determination of Drug Loading Efficiency
- •10.3.8 “In Vitro” Release Studies
- •10.3.8.1 Additives in Microspheres
- •10.4 Sterilization of Microparticles
- •10.5 Calculation of the Dose of Microparticles for Injection
- •10.6 Injectability Studies
- •10.7 In Vivo Studies
- •10.7.1 In Vivo Injection of Microparticles
- •10.7.2 Ocular Disposition and Cellular Uptake
- •10.7.3 Tolerance of Microparticles
- •10.7.4 In Vivo Degradation of PLA and PLGA Microparticles
- •10.8 In Vitro and In Vivo Correlation
- •10.9 Microparticles for the Treatment of Posterior Segment Diseases. Animal Models and Human Studies
- •10.9.1 Proliferative Vitreoretinopathy (PVR)
- •10.9.2 Uveitis
- •10.9.3 Age-Related Macular Degeneration (AMD)
- •10.9.4 Diabetic Retinopathy
- •10.9.5 Macular edema
- •10.9.6 Acute Retinal Necrosis (ARN)
- •10.9.7 Cytomegalovirus (CMV) Retinitis
- •10.9.8 Choroidal Neovascularization
- •10.9.9 Diseases Affecting the Optic Nerve
- •10.9.11 Microparticles in Retinal Repair
- •10.10 Conclusions
- •References
- •11.1 Introduction
- •11.2 Nanoparticles
- •11.2.1 Polymer Nanoparticles
- •11.2.2 Liposomes and Lipid Nanoparticles
- •11.2.3 Micelles
- •11.2.4 Protein Nanoparticles
- •11.2.5 Carbohydrate Nanoparticles
- •11.2.6 Dendrimers
- •11.2.7 Combination Nanosystems
- •11.3 Using Nanotechnology to Improve Ocular Therapeutics
- •11.3.1 Improving Patient Compliance
- •11.3.2 Increasing Drug Retention and Sustained Release
- •11.3.3 Increasing Permeability and Tissue Partitioning
- •11.3.4 Targeting Nanotherapies
- •11.3.5 Intracellular Trafficking
- •11.4 Alternative Approaches to Improve Ocular Therapeutics
- •11.5 Conclusion
- •References
- •12.1 Introduction
- •12.2 Hydrogel Technology
- •12.6 Future Directions
- •References
- •13.1 Introduction
- •13.2 General Design Considerations
- •13.2.1 Administration Site
- •13.2.2 Body Design
- •13.2.3 Port Design
- •13.2.4 Vacuum and Pressure
- •13.2.5 Flushing and Fluid Replacement
- •13.2.5.1 Active Pumps
- •13.2.5.2 Passive Systems
- •13.2.5.3 Solid Refill
- •13.2.6 Contamination Potential
- •13.3 Historical Influences
- •13.3.1 Infusion Pumps
- •13.3.2 Glaucoma Drainage Devices
- •13.3.3 Pioneering of Refill Procedure in the Eye
- •13.4 Ophthalmic Refillable Devices
- •13.4.1 Invasiveness and Refilling Frequency
- •13.4.2 Intravitreal Delivery Through the Pars Plana
- •13.4.3 Episcleral Implantation for Trans-Scleral Delivery
- •13.4.4 Subretinal and Suprachoroidal Implantation
- •13.4.5 Lens Capsule Delivery
- •13.5 Conclusions
- •References
- •14.1 Introduction
- •14.2 Current Methods of Drug Delivery to the Eye
- •14.3 Improved Methods of Drug Delivery to the Eye Using Microneedles
- •14.3.1 Intrastromal Delivery to the Cornea Using Coated Microneedles
- •14.3.3 Suprachoroidal Delivery Using Hollow Microneedles
- •14.4 Microneedle Types and Other Applications
- •14.4.1 Poke and Apply
- •14.4.2 Coat and Poke
- •14.4.3 Poke and Release
- •14.4.4 Poke and Flow
- •14.5 Discussion
- •14.6 Conclusion
- •References
- •15.1 Introduction
- •15.1.1 General Mechanisms of Iontophoretic Drug Delivery
- •15.1.2 The Shunt Pathway
- •15.1.3 The Flip–Flop Gating Mechanism
- •15.1.4 Electro-Osmosis
- •15.2 Ocular Drug Delivery: The Past and the Future
- •15.3 Ophthalmic Applications of Iontophoresis
- •15.3.1 Transconjunctival Iontophoresis
- •15.3.1.1 Transconjunctival Iontophoresis of Antimitotics
- •15.3.1.2 Transconjunctival Iontophoresis of Anesthetics
- •15.3.2 Transcorneal Iontophoresis
- •15.3.2.1 Transcorneal of Fluorescein Iontophoresis for Aqueous Humor Dynamic Studies
- •15.3.2.2 Transcorneal Iontophoresis of Antibiotics
- •15.3.2.3 Transcorneal Iontophoresis of Antiviral Drugs
- •15.3.2.4 Other Drugs for Transcorneal Iontophoresis
- •15.3.2.5 Is Transcorneal Iontophoresis Safe?
- •15.4 Transscleral Iontophoresis
- •15.4.1 Transscleral Iontophoresis of Antibiotics
- •15.4.2 Transscleral Iontophoresis of Antiviral Drugs
- •15.4.3 Transscleral Iontophoresis of Anti-Inflammatory Drugs
- •15.4.3.1 Aspirin
- •15.4.3.2 Glucocorticoids
- •15.4.3.3 Transscleral Iontophoresis of Carboplatin
- •15.4.3.4 Is Transscleral Iontophoresis Safe?
- •15.4.3.5 Transscleral Iontophoresis for High Molecular Weight Compounds and Proteins
- •15.4.3.6 Clinical Application of Transscleral Iontophoresis
- •15.5 Applications of Iontophoresis to Ocular Gene Therapy
- •15.6 Future Developments
- •References
- •16.1 Introduction
- •16.2 Background
- •16.2.1 Intravitreal Injections
- •16.2.2 Impact of Genetics
- •16.3 Better Tools for Delivery and Treatment
- •16.3.1 Barriers to Success
- •16.3.2 Physics-Based Approaches
- •16.3.2.1 Physical Methods to Deliver Drugs to a Target Cell in the Posterior Segment
- •16.3.2.2 History of Electrical Fields in Medicine
- •16.3.2.3 Safety Concerns with Electric Fields
- •16.3.2.4 Definitions of Electric Field Methods
- •16.3.2.5 Advantages of Electric Fields for DNA Transfection vs. Viral Mediated DNA Delivery
- •16.3.2.6 Problems of In Vivo Electric Field Applications
- •16.3.2.7 Possible Strategies to Improve Electric Field-Mediated Drug Delivery
- •16.3.3 Experiences with Iontophoresis
- •16.3.3.1 Examples of Iontophoresis
- •16.3.3.2 Summary of the Strengths and Weaknesses of Iontophoresis
- •16.3.4 Experiences with Electroporation
- •16.3.4.1 Examples of Electroporation in Living Animals
- •16.3.4.2 Strengths and Weaknesses of Electroporation
- •16.4 Outstanding Issues in Electric Fields for the Delivery of Drugs
- •16.5 Summary
- •References
- •17.1 Introduction
- •17.2 Routes of Protein Administration
- •17.2.1 Topical
- •17.2.2 Intracameral
- •17.2.3 Intravitreal
- •17.2.4 Periocular (Transscleral)
- •17.2.5 Suprachoroidal
- •17.2.6 Subretinal
- •17.2.7 Systemic
- •17.3 Advantages and Challenges of Protein Delivery
- •17.4 Current Development Strategies
- •17.4.1 Pure Protein
- •17.4.2 PEGylation
- •17.4.4 Liposomes
- •17.4.5 Stem Cells
- •17.4.6 Implants
- •17.5 Case Studies
- •17.6 Ophthalmic Protein Formulation Development
- •17.6.1 Protein Biosynthesis
- •17.6.2 Preformulation Studies
- •17.6.3 Selection of Excipients
- •17.6.4 Optimization of Process Variables
- •17.7 Specifications and Regulatory Guidelines
- •17.8 Conclusions
- •References
- •18.1 Need for Suspension Development for the Back of the Eye
- •18.2 Background
- •18.3 Development of Drug Suspensions Intended for the Back of the Eye
- •18.3.1 Drug Suspensions
- •18.3.1.1 Physical Pharmacy Principles that Explain the Stability and Formulation of Suspensions
- •18.3.1.2 Formulation Methodology
- •18.3.1.3 Manufacturing Process
- •18.3.2 Factors To Be Considered in Suspension Development for the Back of the Eye
- •18.3.2.1 Formulation Development and Evaluation
- •18.3.2.2 In Situ Forming Suspensions, Selection of Drug Form for Suspension, and Polymeric Microparticle Suspension
- •18.3.2.3 Clinical Studies on Safety
- •18.4 Conclusions
- •References
- •19.1 Introduction
- •19.2 Drug Product Approval Process
- •19.3 Considerations for Back of the Eye Treatments
- •19.4 Adaptive Trial Design
- •19.5 Drug-Device Combinations
- •19.6 Product Summary Basis of Approval Reviews
- •19.6.1 OZURDEX™
- •19.6.2 LUCENTIS™
- •19.7 Summary
- •References
- •20.1 Background
- •20.2 FDA Endpoints
- •20.3 Endpoints for Neovascular Age-Related Macular Degeneration (Table 20.1)
- •20.4 FDA Guidelines for Other Retinal Diseases
- •20.5 Endpoint for Geographic Atrophy
- •20.6 Endpoint for Retinal Vein Occlusion
- •20.7 Future Endpoints
- •References
- •21.1 Introduction
- •21.2 Ocular Physiology and Pathology
- •21.2.1 Ocular Inflammation
- •21.2.2 Neovascularization
- •21.2.3 Degeneration
- •21.3 Current Therapies for Key Back of the Eye Disorders
- •21.3.1 Age-Related Macular Degeneration
- •21.3.1.1 Pathophysiology
- •21.3.1.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.1.3 Current Research Focused on Identifying New Targets
- •21.3.2 Diabetic Retinopathy
- •21.3.2.1 Pathophysiology
- •21.3.2.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.3 Retinopathy of Prematurity
- •21.3.3.1 Pathophysiology
- •21.3.3.2 Therapeutics Either in Current Use and in Clinical Trials
- •21.3.4 Degenerative Conditions
- •21.3.4.1 Pathophysiology
- •21.3.4.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.5 Opportunistic Infections
- •21.3.5.1 Pathophysiology
- •21.3.5.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.6 Autoimmune Disease
- •21.3.6.1 Pathophysiology
- •21.3.6.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.4 Conclusion
- •References
- •22.1 Bile Acids as Anti-Apoptotic Neuroprotectants
- •22.3 Potential Need for Local Delivery of Bile Acids as Neuroprotectants
- •22.4 Preliminary Studies of Ocular Delivery of Bile Acids
- •22.5 Conclusion
- •References
- •Index
Contents
1 Selection of Drug Delivery Approaches for the Back of the Eye: |
|
Opportunities and Unmet Needs............................................................ |
1 |
David A. Marsh |
|
2 Microdialysis for Vitreal Pharmacokinetics.......................................... |
21 |
Ravi D. Vaishya, Hari Krishna Ananthula, and Ashim K. Mitra |
|
3 Fluorophotometry for Pharmacokinetic Assessment........................... |
47 |
Bernard E. McCarey |
|
4 Systemic Route for Retinal Drug Delivery: |
|
Role of the Blood-Retinal Barrier.......................................................... |
85 |
Masanori Tachikawa, Vadivel Ganapathy, and Ken-ichi Hosoya |
|
5 Topical Drug Delivery to the Back of the Eye....................................... |
111 |
Thomas Gadek and Dennis Lee |
|
6 Principles of Retinal Drug Delivery from Within the Vitreous........... |
125 |
Clive G. Wilson, Lay Ean Tan, and Jenifer Mains |
|
7 Transscleral Drug Delivery..................................................................... |
159 |
Dayle H. Geroski and Henry F. Edelhauser |
|
8 Suprachoroidal and Intrascleral Drug Delivery................................... |
173 |
Timothy W. Olsen and Brian C. Gilger |
|
9 Advances in Biodegradable Ocular Drug Delivery Systems................ |
185 |
Susan S. Lee, Patrick Hughes, Aron D. Ross, |
|
and Michael R. Robinson |
|
10 Microparticles as Drug Delivery Systems |
|
for the Back of the Eye............................................................................ |
231 |
Rocío Herrero-Vanrell |
|
11 Nanotechnology and Nanoparticles....................................................... |
261 |
Shelley A. Durazo and Uday B. Kompella |
|
vii
viii |
|
Contents |
12 |
Hydrogels for Ocular Posterior Segment Drug Delivery..................... |
291 |
|
Gauri P. Misra, Thomas W. Gardner, and Tao L. Lowe |
|
13 |
Refillable Devices for Therapy of Ophthalmic Diseases...................... |
305 |
|
Alan L. Weiner |
|
14 |
Targeted Drug Delivery to the Eye Enabled by Microneedles............ |
331 |
|
Samirkumar R. Patel, Henry F. Edelhauser, |
|
|
and Mark R. Prausnitz |
|
15 |
Ocular Iontophoresis............................................................................... |
361 |
|
Francine F. Behar-Cohen, Peter Milne, Jean-Marie Parel, |
|
|
and Indu Persaud |
|
16 |
Drug and Gene Therapy Mediated by Physical Methods.................... |
391 |
|
John M. Nickerson and Jeffrey H. Boatright |
|
17 |
Protein Drug Delivery and Formulation Development........................ |
409 |
|
Rinku Baid, Puneet Tyagi, Shelley A. Durazo, |
|
|
and Uday B. Kompella |
|
18 |
Drug Suspension Development for the Back of the Eye....................... |
449 |
|
Jithan Aukunuru, Puneet Tyagi, Chandrasekar Durairaj, |
|
|
and Uday B. Kompella |
|
19 |
Regulatory Considerations in Product Development |
|
|
for Back of the Eye.................................................................................. |
469 |
|
Ashutosh A. Kulkarni |
|
20 |
Clinical Endpoints for Back of the Eye Diseases.................................. |
485 |
|
Karl G. Csaky |
|
21 |
Druggable Targets and Therapeutic Agents for Disorders |
|
|
of the Back of the Eye.............................................................................. |
495 |
|
Robert I. Scheinman, Sunil K. Vooturi, and Uday B. Kompella |
|
22 |
Development of Bile Acids as Anti-Apoptotic |
|
|
and Neuroprotective Agents in Treatment of Ocular Disease............. |
565 |
|
Stephanie L. Foster, Cristina Kendall, Allia K. Lindsay, |
|
|
Alison C. Ziesel, Rachael S. Allen, Sheree S. Mosley, |
|
|
Esther S. Kim, Ross J. Molinaro, Henry F. Edelhauser, |
|
|
Machelle T. Pardue, John M. Nickerson, |
|
|
and Jeffrey H. Boatright |
|
Index................................................................................................................. |
577 |
|
Contributors
Rachael S. Allen, MS Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
Hari Krishna Ananthula, MS Division of Pharmaceutical Sciences, University of Missouri-Kansas City, School of Pharmacy, Kansas City, MO, USA
Jithan Aukunuru, PhD Mother Teresa College of Pharmacy, Hyderabad, India
Rinku Baid, B.Pharm Nanomedicine and Drug Delivery Laboratory, University of Colorado, Aurora, CO, USA
Francine F. Behar-Cohen, MD, PhD Université Paris Descartes, Assistance Publique Hôpitaux de Paris, Paris, France
Jeffrey H. Boatright, PhD Department of Ophthalmology,
Emory University School of Medicine, Atlanta, GA, USA
Karl G. Csaky, MD, PhD Sybil Harrington Molecular Laboratory, Retina Foundation of the Southwest, Dallas, TX, USA
Chandrasekar Durairaj, PhD Nanomedicine and Drug Delivery Laboratory, University of Colorado, Aurora, CO and Allergan, Inc., Irvine, CA, USA
Shelley A. Durazo, BS Nanomedicine and Drug Delivery Laboratory, University of Colorado, Aurora, CO, USA
Henry F. Edelhauser, PhD Emory University Eye Center, Emory University, Atlanta, GA, USA
Stephanie L. Foster Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
Thomas Gadek, PhD OphthaMystic Consulting, Oakland, CA, USA
Vadivel Ganapathy, PhD Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA, USA
ix
x |
Contributors |
Thomas W. Gardner, PhD Department of Ophthalmology, Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA, USA
Dayle H. Geroski, PhD Emory University School of Medicine, Eye Center, Atlanta, GA, USA
Brian C. Gilger, DVM MS Dipl. ACVO, Dipl. ABT Department of Ophthalmology, College of Veterinary Medicine, North Carolina State University, Raleigh,
NC, USA
Rocío Herrero-Vanrell, PhD Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain
Ken-ichi Hosoya, PhD Department of Pharmaceutics, Graduate School
of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Patrick Hughes, PhD Allergan, Inc., Irvine, CA, USA
Cristina Kendall, MS Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
Esther S. Kim, BS Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
Uday B. Kompella, PhD Nanomedicine and Drug Delivery Laboratory Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
Department of Ophthalmology, University of Colorado, Aurora, CO, USA
Ashutosh A. Kulkarni, PhD Department of Pharmacokinetics, and Drug Disposition, Allergan Inc., Irvine, CA, USA
Dennis Lee, PhD Ophthiris, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA
Susan S. Lee, MS Allergan, Inc., Irvine, CA, USA
Allia K. Lindsay, BS Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
Tao L. Lowe, PhD Department of Pharmaceutical Sciences, School of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USA
Department of Pharmaceutical Sciences, College of Pharmacy University of Tennessee Health Science Center, Memphis, TN, USA
Jenifer Mains, M.Pharm Strathclyde Institute of Pharmaceutical
and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK
David A. Marsh, PhD Texas Tech University Health Science Center, School of Pharmacy, Abilene, TX, USA
Contributors |
xi |
Bernard E. McCarey, PhD Emory University School of Medicine, Eye Center, Atlanta, GA, USA
Peter Milne, PhD Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA
Gauri P. Misra, PhD Department of Pharmaceutical Sciences,
Thomas Jefferson University, School of Pharmacy, Philadelphia, PA, USA
Ashim K. Mitra, PhD Division of Pharmaceutical Sciences,
University of Missouri-Kansas City, School of Pharmacy, Kansas City, MO, USA
Ross J. Molinaro, PhD Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
Sheree S. Mosley, BS Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
John M. Nickerson, PhD Department of Ophthalmology, Emory University, Atlanta, GA, USA
Timothy W. Olsen, MD Department of Ophthalmology, Emory Eye Center, Emory University School of Medicine, Atlanta, GA, USA
Machelle T. Pardue, PhD Department of Ophthalmology and Rehabilitation Research and Development Center of Excellence, Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, GA, USA
Jean-Marie Parel, PhD Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA
Samirkumar R. Patel, PhD School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA
Indu Persaud, MS Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
Mark R. Prausnitz, PhD School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA
Michael R. Robinson, MD Allergan, Inc., Irvine, CA, USA
Aron D. Ross, PhD Triton Biomedical, Inc., Laguna Beach, CA, USA
Robert I. Scheinman, PhD Department of Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
Masanori Tachikawa, PhD Department of Pharmaceutics,
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
Lay Ean Tan, PhD Strathclyde Institute of Pharmaceutical and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK
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Contributors |
Puneet Tyagi, M.Pharm Nanomedicine and Drug Delivery Laboratory, University of Colorado, Aurora, CO, USA
Ravi D. Vaishya, B.Pharm Division of Pharmaceutical Sciences,
University of Missouri-Kansas City, School of Pharmacy, Kansas City, MO, USA
Sunil K. Vooturi, PhD Nanomedicine and Drug Delivery Laboratory, University of Colorado, Aurora, CO, USA
Alan L. Weiner, PhD DrugDel Consulting, LLC, Arlington, TX, USA
Clive G. Wilson, PhD Strathclyde Institute of Pharmaceutical
and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK
Alison C. Ziesel, BS Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA
Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada