the advances and challenges in ocular drug delivery via implantation techniques
DESCRIPTION
The Advances and Challenges in Ocular Drug Delivery via Implantation Techniques. Silicone cup containing drug. EFFECT OF ENVIRONMENT AND CLOZAPINE ON BASAL AND STIMULATED MEDIAL PREFRONTAL GABA RELEASE IN TWO RAT MODELS OF SCHIZOPHRENIA. Top View. Release orifice. 3mm. - PowerPoint PPT PresentationTRANSCRIPT
EFFECT OF ENVIRONMENT AND CLOZAPINE ON BASAL AND STIMULATED MEDIAL PREFRONTAL GABA RELEASE IN TWO
RAT MODELS OF SCHIZOPHRENIA
The Advances and Challenges in Ocular Drug Delivery via Implantation Techniques
Adedoyin Awodele, Faye Carrington, Alanna Cavanagh, Sarah Kileen, Melissa MacPherson.
Pharmacology, UCD School of Biomolecular and Biomedical Science, University College Dublin, Ireland.
References
Why Implants?
What are they?•.Usually made of polymers that release a drug over a prolonged period of time. There are two types:
• Provide sustained drug delivery to the posterior or anterior segment of the eye
• Can be applied to various ocular layers depending
on disease: subconjuctival/intravitreal/intrasceral
• Implants reduce frequency of administration compared to I.V. Route in relation to treating diseases of the posterior segment, therefore they reduce risk of SEs
• Minimise the importance of patient compliance.
Above: Insertion of Retisert
Ocular drug barriers:
FDA approved in 1996, Vitrasert was first non-biodegradable, intravitreal implant. Used for the delivery of the anti-viral
drug, ganciclovir to treat AIDs-related Cytomegalovirus (CMV) Retinitis.
Ganciclovir is a synthetic analogue of the nucleoside 2-deoxyguanosine, which causes chain termination, preventing
replication. Each implant holds 4.5-5mg of the prodrug which is released at a rate of approx. 1-1.5µg/hr over 5-8 months.
The 4mm device consists of a compressed drug pellet core which is completely
covered, except at its top surface, with the impermeable polymer; EVA. This entire
assembly is then coated by the permeable polymer; (PVA).
Surgical Implantation The implant is inserted by making a 5-6mm scleral incision into the pars plana. It
is then fixed into place using sutures. The wound is closed and a saline solution is injected to restore normal ocular pressure.
Most patients experience blurred vision which usually clears between 2-4 weeks after surgery.
Retisert• For treatment of chronic, non-infectious uveitis (inflammation) including
sympathetic ophthalmia. • 3mm x 2mm x 5mm in size• Reservoir of flucinolone acetonide (corticosteroid thought to act by
inducing phospholipase A2 inhib. proteins). 600ng a day decreasing to 300-400ng over the first month.
• Inserted through the pars plana into the vitreous humour• Active for 2 and a half years• Removal can cause problems• SEs = Cataracts (observed in 90% of patients after 3 years), increased
I.O pressure, eye pain, headache, nasopharyngitis and joint pain.
Top View
Side View
Silicone cup containing
drug Release orifice
PVA structure
tab
5mm
2mm
3mm
• 0.59mg tablet is held in a silicone elastomer
cup.
• The release orifice is separated from the
drugby a PVA membrane.
• The structure is held together with silicone
glue
OzurdexOzurdex is a biodegradable implant that contains demaxethasone. It is an intravitreal implant that delivers a sustained release of demaxaethasone (700ml) to the retina and vitreous humour. Ozurdex can improve visual acuity and macular thickness. It is used to treat macular edema, Retinal vein occlusion and non-infectious uveitis (posterior).
Iluvien• Recently approved as a treatment for DME• It weighs 0.18mg and dispenses 0.2µg of the drug daily• It is the only drug therapy for DME treatment• In phase II trials for the treatment of wet and dry AMD and
RVO• Active ingredient is fluocinolone acetonide
DELIVERY• injected intra-vitreally using a 25
gauge needle.• minimally invasive procedure, no
need for suture• Non-erodible insert• Designed to deliver drug for up to 3
years• Easier to deliver then retisert
because of its smaller size
Diseases of the Eye• Age-related Macular Degeneration (AMD) : Damage to
retina by accumulation of drusen can cause loss of central vision.
• Diabetic Retinopathy is a type of retinal damage that can lead to blindness caused by microvascular changes due to diabetes mellitus.
• Glaucoma is caused by damage to the optic nerve by loss of retinal ganglion cells and increased fluid pressure in the eye.
• Retinitis Pigmentosa is a progressive retinal dystrophy which affects the photoreceptors and causes loss of peripheral vision and eventually central vision.
• CMV Retinitis is a chronic, infection of the retina caused by the cytomegalovirus. Predominantly affects immunosuppressed individuals and estimated to affect 15-40% of AIDS patients.
• Diabetic Macular Edema (DME) is the most common cause of visual loss and is characterised by accumulation of extracellular fluid in the macular which occurs after the break down of the blood-retinal barrier due to dilated hyper-capillaries and micro-aneurysms..
• Uveitis is the swelling and irritation of the uvea (anterior segment) and can be caused by autoimmune disorders, infection or exposure to toxins.
Retinal Detachment
Vitreous Haemorrhage
Cystoid Macular Oedema
Endophthalimitis
Advances in Implants/ Developments
Implant Type: Biodegradable Non-Biodegradable
Pros: Will be cleared from body naturally, no need for surgical removal.
Drug release can be controlled more precisely.
Cons: Controlof drug release from degradable systems is more difficult.
Must be surgically removed.
Future Perspectives
Non
-Bio
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Impl
ants
Vitrasert
Structure
Dynamic: Static:
•Tear Dilution- max. only 30µl tear volume comfortably accomm. In eye when the average eye drop is 50 µl in volume – inevitable spillage!•Naso-lacrimal duct- when tears exceed normal tear volume of 7-10 µl•Systemic Removal – the conjunctiva is highly vascularised and any drug permeating it is rapidly removed by the systemic circulation and eventually transported to the GIT.
•Cornea-Hydrophobic and hydrophilic layers connected by tight junctions and containing efflux pumps inducing multidrug resistance. (p-glycoprotein and MRP)•Sclera-Opaque matrix of proteoglycans and collagen that acts as a filter with preferred permeability for small, hydrophilic and positively charged molecules due to it’s structure.•Blood-Ocular Barriers –the blood-retinal barrier arises from the retinal pigment epithelium prevents transfer of molecules between itself and choroidal blood with tight junctions and according to some studies show P-gp efflux pumps present also.
Introduction
Why Ozurdex? Why not Ozurdex?
•It’s potency•Dose consistency•Extended Duration of action•Minimal adverse effects•Biodegradable nature- It does not need to be retrieved and can be administered repeatedly.
• Shorter duration of action compared to retinal vein occlusion.
• Retention of the implant in the correct position can be challenging.
• Can cause cataract formation, IOP elevation, subconjuntival hemorrhage, hyperemia or conjunctival edema.
Implants Vs. Other Delivery
Side Effects and Complications of Implants