- •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
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2.5 Vitreal Pharmacokinetics in Animals Other than Rabbits
Rabbits have been the choice of species for vitreal pharmacokinetic studies. However, time to time, various other animal species have also been employed including rats, birds, cats and zebrafish to study physiology of ocular tissues.
Ebihara et al. (1997) measured melatonin levels in pineal and retinal tissues to understand role of melatonin in avian circadian rhythm with permanently implanted microdialysis probes in the eye and pineal gland. After a recovery period of few days, birds were subjected to light–dark cycle and melatonin release was measured. Antiphase relation between dopamine and melatonin release was also confirmed by simultaneous measurements of dopamine and melatonin. In a similar study, Puppala et al. (2004) investigated the effects of light and dark cycles on dopamine release from retina utilizing microdialysis in anesthetized zebrafish. Dopamine release was found to be elevated for transition from dark to flickering light and decreased for shift from flickering light to dark. Shift from dark to steady light and steady light to dark had no influence on dopamine release.
Several investigators have developed microdialysis models with rats despite small size of globe. However, anatomically rat eyes are similar to human eyes and show the presence of highly vascularized retina (Pow 2001). In comparison to rats, rabbits have poorly vascularized retina and most of the dose enters retina via choroidal circulation which is separated from retina by RPE (outer BRB) (Pow 2001; Sen et al. 1992). Katayama et al. (2006) studied the influence of organic anion transporter (OAT) on the passage of estradiol 17-b-glucoronide (E17bG) across BRB utilizing microdialysis in an anesthetized rat model. Custom designed concentric probes were inserted in vitreous humor with the help of 25-G needle, 1 mm below limbus. Dialysis tube with MWCO of 50 kDa was employed and probes were circulated with Ringer-HEPES solution at 2 mL/min at 37°C. Following probe insertion, [3H]E17bG and [14C]mannitol (marker of paracellular permeability) were injected intravitreally. For inhibition studies, known substrates of OAT were perfused through dialysis probe throughout the experiment and [3H] E17bG was given intravitreally. [3H]E17bG and [14C]mannitol showed bi-exponential elimination kinetics from vitreous and [3H]E17bG had 1.9-fold higher elimination rate constant compared to [14C]mannitol. Involvement of OAT system was confirmed with inhibition studies, where elimination rate for [3H]E17bG decreased in the presence of OAT substrates such as sulfobromophthalein, probenecid, digoxin and dehydroepiandrosterone sulfate. The elimination rate constant was unchanged for [14C]mannitol, which indicated a transporter system for [3H]E17bG and intactness of BRB. In similar study, Hosoya et al. (2009) employed microdialysis to confirm the functional expression of OAT3 in inner BRB, in rats. In another study, Yoneyama et al. (2010) employed microdialysis and studied vitreal pharmacokinetics of L-proline to identify functional presence of system. A transporter system in retinal blood capillaries is an anesthetized rat model. Thus, rat model offers distinct advantage over rabbit models due to the presence of highly
2 Microdialysis for Vitreal Pharmacokinetics |
43 |
vascularized retina. This blood supply together with the presence of several transporter systems may considerably influence elimination of various molecules via the transretinal route.
2.6 Summary
Microdialysis has become an instrumental sampling technique to study posterior segment pharmacokinetics without sacrificing a huge number of animals. It has undergone significant transformations in the last decade and currently several animal models have been established for sampling inaccessible posterior segment tissues such as vitreous humor. Remarkable progress has been made in the probe design and validation techniques. Ocular microdialysis has been widely utilized in studying drug disposition and determining functional existence of transporters in retina. However, several experimental conditions such as probe design, recovery period, perfusate flow rate, anesthesia, tissue trauma and validation of animal model may influence obtained pharmacokinetic profile. Flow rate should be carefully adjusted to have enough sample volume at particular time points with good recovery in order to avoid issues related to analysis. Anesthesia significantly influences drug elimination by altering IOP, heart rate and respiratory rate. Choice of animal for microdialysis primarily depends on the objective of the study. The tissue damage could result in increased protein concentration or may affect integrity of BRB. The tissue trauma due to probe insertion method may significantly alter the pharmacokinetic profile. The animal model must be validated before performing the studies. The abovementioned parameters should be carefully optimized for studying ocular pharmacokinetics. So far, microdialysis has provided valuable information in the assessment of drug disposition in posterior segment and is expected to provide useful information to develop novel ocular therapeutics.
Acknowledgment Supported by National Institutes of Health grants R01EY 09171–16 and R01EY 10659–14.
References
Adachi A, Hasegawa M, Ebihara S (1995) Measurement of circadian rhythms of ocular melatonin in the pigeon by in vivo microdialysis. Neuroreport 7:286–288
Adachi A, Nogi T, Ebihara S (1998) Phase-relationship and mutual effects between circadian rhythms of ocular melatonin and dopamine in the pigeon. Brain Res 792:361–369
Amberg G, Lindefors N (1989) Intracerebral microdialysis: II. Mathematical studies of diffusion kinetics. J Pharmacol Methods 22:157–183
Anand BS, Atluri H, Mitra AK (2004) Validation of an ocular microdialysis technique in rabbits with permanently implanted vitreous probes: systemic and intravitreal pharmacokinetics of fluorescein. Int J Pharm 281:79–88
44 |
R.D. Vaishya et al. |
Atluri H, Mitra AK (2003) Disposition of short-chain aliphatic alcohols in rabbit vitreous by ocular microdialysis. Exp Eye Res 76:315–320
Atluri H, Talluri RS, Mitra AK (2008) Functional activity of a large neutral amino acid transporter (lat) in rabbit retina: a study involving the in vivo retinal uptake and vitreal pharmacokinetics of l-phenyl alanine. Int J Pharm 347:23–30
Ben-Nun J, Cooper RL, Cringle SJ, Constable IJ (1988) Ocular dialysis. A new technique for in vivo intraocular pharmacokinetic measurements. Arch Ophthalmol 106:254–259
Dias CS, Mitra AK (2003) Posterior segment ocular pharmacokinetics using microdialysis in a conscious rabbit model. Invest Ophthalmol Vis Sci 44:300–305
Duvvuri S, Gandhi MD, Mitra AK (2003) Effect of p-glycoprotein on the ocular disposition of a model substrate, quinidine. Curr Eye Res 27:345–353
Duvvuri S, Janoria KG, Pal D, Mitra AK (2007) Controlled delivery of ganciclovir to the retina with drug-loaded poly(d, l-lactide-co-glycolide) (plga) microspheres dispersed in plga-peg-plga gel: a novel intravitreal delivery system for the treatment of cytomegalovirus retinitis. J Ocul Pharmacol Ther 23:264–274
Ebihara S, Adachi A, Hasegawa M, Nogi T, Yoshimura T, Hirunagi K (1997) In vivo microdialysis studies of pineal and ocular melatonin rhythms in birds. Biol Signals 6:233–240
Gunnarson G, Jakobsson AK, Hamberger A, Sjostrand J (1987) Free amino acids in the pre-retinal vitreous space. Effect of high potassium and nipecotic acid. Exp Eye Res 44:235–244
Hosoya K, Makihara A, Tsujikawa Y, Yoneyama D, Mori S, Terasaki T, Akanuma S, Tomi M, Tachikawa M (2009) Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mer- captopurine. J Pharmacol Exp Ther 329:87–93
Hughes PM, Krishnamoorthy R, Mitra AK (1996) Vitreous disposition of two acycloguanosine antivirals in the albino and pigmented rabbit models: a novel ocular microdialysis technique. J Ocul Pharmacol Ther 12:209–224
Janoria KG, Boddu SH, Wang Z, Paturi DK, Samanta S, Pal D, Mitra AK (2009) Vitreal pharmacokinetics of biotinylated ganciclovir: role of sodium-dependent multivitamin transporter expressed on retina. J Ocul Pharmacol Ther 25:39–49
Kalant H (1958) A microdialysis procedure for extraction and isolation of corticosteroids from peripheral blood plasma. Biochem J 69:99–103
Katayama K, Ohshima Y, Tomi M, Hosoya K (2006) Application of microdialysis to evaluate the efflux transport of estradiol 17-beta glucuronide across the rat blood-retinal barrier. J Neurosci Methods 156:249–256
Louzada-Junior P, Dias JJ, Santos WF, Lachat JJ, Bradford HF, Coutinho-Netto J (1992) Glutamate release in experimental ischaemia of the retina: an approach using microdialysis. J Neurochem 59:358–363
Macha S, Mitra AK (2001) Ocular pharmacokinetics in rabbits using a novel dual probe microdialysis technique. Exp Eye Res 72:289–299
Majumdar S, Kansara V, Mitra AK (2006) Vitreal pharmacokinetics of dipeptide monoester prodrugs of ganciclovir. J Ocul Pharmacol Ther 22:231–241
Maurice DM (1957) The exchange of sodium between the vitreous body and the blood and aqueous humour. J Physiol 137:110–125
Maurice DM (1959) Protein dynamics in the eye studied with labelled proteins. Am J Ophthalmol 47:361–368
Pow DV (2001) Amino acids and their transporters in the retina. Neurochem Int 38:463–484 Puppala D, Maaswinkel H, Mason B, Legan SJ, Li L (2004) An in vivo microdialysis study of
light/dark-modulation of vitreal dopamine release in zebrafish. J Neurocytol 33:193–201 Rittenhouse KD, Pollack GM (2000) Microdialysis and drug delivery to the eye. Adv Drug Deliv
Rev 45:229–241
Sen HA, Berkowitz BA, Ando N, de Juan E Jr (1992) In vivo imaging of breakdown of the inner and outer blood-retinal barriers. Invest Ophthalmol Vis Sci 33:3507–3512
Stempels N, Tassignon MJ, Sarre S, Nguyen-Legros J (1994) Microdialysis measurement of catecholamines in rabbit vitreous after retinal laser photocoagulation. Exp Eye Res 59:433–439
2 Microdialysis for Vitreal Pharmacokinetics |
45 |
Tagami M, Kusuhara S, Honda S, Tsukahara Y, Negi A (2009) Expression of ATP-binding cassette transporters at the inner blood-retinal barrier in a neonatal mouse model of oxygen-induced retinopathy. Brain Res 1283:186–193
Ungerstedt U, Pycock C (1974) Functional correlates of dopamine neurotransmission. Bull Schweiz Akad Med Wiss 30:44–55
Waga J, Ehinger B (1995) Passage of drugs through different intraocular microdialysis membranes. Graefes Arch Clin Exp Ophthalmol 233:31–37
Waga J, Ohta A, Ehinger B (1991) Intraocular microdialysis with permanently implanted probes in rabbit. Acta Ophthalmol (Copenh) 69:618–624
Waga J, Nilsson-Ehle I, Ljungberg B, Skarin A, Stahle L, Ehinger B (1999) Microdialysis for pharmacokinetic studies of ceftazidime in rabbit vitreous. J Ocul Pharmacol Ther 15:455–463 Wages SA, Church WH, Justice JB Jr (1986) Sampling considerations for on-line microbore liquid
chromatography of brain dialysate. Anal Chem 58:1649–1656
Wang Y, Wong SL, Sawchuk RJ (1993) Microdialysis calibration using retrodialysis and zero-net flux: application to a study of the distribution of zidovudine to rabbit cerebrospinal fluid and thalamus. Pharm Res 10:1411–1419
Yoneyama D, Shinozaki Y, Lu WL, Tomi M, Tachikawa M, Hosoya K (2010) Involvement of system A in the retina-to-blood transport of l-proline across the inner blood-retinal barrier. Exp Eye Res 90:507–513