Ozurdex and Novadur Implant Sustained Dexamethasone Drug Delivery

  • Slides: 19
Download presentation
Ozurdex and Novadur Implant Sustained Dexamethasone Drug Delivery System First approved pharmacotherapy for macular

Ozurdex and Novadur Implant Sustained Dexamethasone Drug Delivery System First approved pharmacotherapy for macular edema following BRVO and CRVO Dr. Bharti Kashyap Memorial Eye Hospital

�A biodegradable dexamethasone implant • Drug incorporated into polymer matrix • Sustained medication release

�A biodegradable dexamethasone implant • Drug incorporated into polymer matrix • Sustained medication release • Polymer matrix gradually breaks down into inert compounds • Extruded form is implanted with an applicator – the NOVADUR™ implant �Self-sealing wound

NOVADUR™ implant • Rod shaped tiny implant • 0. 45 mm in diameter and

NOVADUR™ implant • Rod shaped tiny implant • 0. 45 mm in diameter and 6 mm in length • Contains 0. 7 mg of Dexamethasone (preservative free) • Novadur is a proprietary and innovative drug delivery system (DDS). • Dexamethasone embedded in an inactive biodegradable PLGA matrix. (60/40 drug/polymer)

Applicator and NOVADUR™ implant

Applicator and NOVADUR™ implant

Drug Release From Biodegradable Implants Three Phases of Release Surface Release

Drug Release From Biodegradable Implants Three Phases of Release Surface Release

Drug Release From Biodegradable Implants Three Phases of Release Diffusion

Drug Release From Biodegradable Implants Three Phases of Release Diffusion

Drug Release From Biodegradable Implants Three Phases of Release Bulk Erosion

Drug Release From Biodegradable Implants Three Phases of Release Bulk Erosion

Drug Delivery Technology Biodegradable Implant Gradually Transforms Into Water and Carbon Dioxide Lactic Acid

Drug Delivery Technology Biodegradable Implant Gradually Transforms Into Water and Carbon Dioxide Lactic Acid Glycolic Acid Water and Carbon Dioxide

Changes in Polymer Matrix Over Time Before Implantation After 3 Weeks

Changes in Polymer Matrix Over Time Before Implantation After 3 Weeks

� Implanted with 22 -gauge applicator • Through the pars plana � Wound is

� Implanted with 22 -gauge applicator • Through the pars plana � Wound is self-sealing • No sutures required � Implant does not need to be sutured into place

Inflammation: a key component in the pathogenesis of retinal disease 1, 2 Retinal vein

Inflammation: a key component in the pathogenesis of retinal disease 1, 2 Retinal vein occlusion (RVO)1 Uveitis 1 Inflammation Neovascularisation Wet age-related macular degeneration (wet AMD)2 1. Johnson MW. Am J Ophthalmol 2009; 147: 11– 21; 2. Nowak JZ. Pharmacol Rep 2006; 58: 353– 63. Vascular leakage Diabetic retinopathy (DR)/ diabetic macular edema (DME)1 Retinal disease

Pathophysiology Corticosteroid-Based Therapies Vascular Disease Diabetes CRVO/ BRVO Healthy Retinal Microvessel Inflammatory Mediator IL-1,

Pathophysiology Corticosteroid-Based Therapies Vascular Disease Diabetes CRVO/ BRVO Healthy Retinal Microvessel Inflammatory Mediator IL-1, 6, 8 TNF-Alpha VEGF Vasodilation Leukostasis Primary Inflammatory Disease Uveitis Diapedesis Permeability Macular Edema Inflammatory proteins

Corticosteroid-Based Therapies � Corticosteroids inhibit the inflammatory response to a variety of inciting agents.

Corticosteroid-Based Therapies � Corticosteroids inhibit the inflammatory response to a variety of inciting agents. � They inhibit the edema formation, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, deposition of collagen, and scar formation associated with inflammation � They stabilize endothelial cells tight junctions, inhibit the synthesis of VEGF, prostaglandins & other key cytokines.

Corticosteroid-Based Therapies � Arachidonic acid is released from membrane phospholipids by phospholipase A 2.

Corticosteroid-Based Therapies � Arachidonic acid is released from membrane phospholipids by phospholipase A 2. � It is postulated that lipocortins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. � Corticosteroids are thought to act by the induction of phospholipase A 2 inhibitory proteins, collectively called lipocortins.

Arachidonic acid Corticosteroids Phospholipase A 2. Prostaglandins Leukotrienes lipocortins

Arachidonic acid Corticosteroids Phospholipase A 2. Prostaglandins Leukotrienes lipocortins

Pathophysiology Corticosteroid-Based Therapies Vascular Disease Diabetes CRVO/ BRVO VEGF Vasodilation Leukostasis Healthy Retinal Microvessel

Pathophysiology Corticosteroid-Based Therapies Vascular Disease Diabetes CRVO/ BRVO VEGF Vasodilation Leukostasis Healthy Retinal Microvessel Primary Inflammatory Disease Uveitis Corticosteroids Diapedesis Permeability Macular Edema Inflammatory Mediator IL-1 TNF-Alpha Inflammatory proteins

Relative Potencies of Corticosteroids Corticosteroid Cortisone Cortisol Prednisone Relative Potencies 0. 8 1 4

Relative Potencies of Corticosteroids Corticosteroid Cortisone Cortisol Prednisone Relative Potencies 0. 8 1 4 Methylprednisolone 5 Triamcinolone 5 Betamethasone 25 Dexamethasone Fluocinolone acetonide 25 25* Table 59 -2 Goodman & Gilman 9 th Edition *approximated from the literature Fluorination at 9 position increases corticosteroid receptor binding

�Desired characteristics of an implantable intravitreal drug delivery system • Controlled, sustained drug release

�Desired characteristics of an implantable intravitreal drug delivery system • Controlled, sustained drug release • Simple insertion procedure • Biodegradable implant (does not need to be removed) • Long-term safety

Thank You

Thank You