Lecture 13 ocular drug delivery

Question 1

Describe the challenges associated with ocular drug delivery via eye drops. What factors influence the absorption of drugs through eye drops?

Answer 1

Ocular drug delivery through eye drops faces challenges like limited uptake, tear dilution, and poor availability. Factors influencing drug absorption include solubility, charge, pH, and molecular size (< 500 daltons).

Question 2

How does direct injection in the eye, specifically intravitreal injection, differ from periocular injections in terms of drug delivery to the posterior segment of the eye?

Answer 2

Direct intravitreal injection involves injecting medication directly into the vitreous humor, while periocular injections are administered on the outer surface of the eye. Intravitreal injections are more invasive and require smaller volumes, leading to non-uniform drug distribution.

Question 3

Define periocular injections and explain how they facilitate drug delivery to the posterior segment of the eye. What factors influence drug diffusion in periocular injections?

Answer 3

Periocular injections involve injecting drugs on the outer surface of the eye to achieve therapeutic concentrations in the posterior segment. Drug diffusion across the sclera depends on factors like solubility, molecular weight, charge, and polarity.

Question 4

What are the advantages and disadvantages of using direct intravitreal injections for ocular drug delivery? How does drug distribution differ in intravitreal injections compared to other routes?

Answer 4

Direct intravitreal injections offer direct drug delivery to the posterior segment but are invasive and require frequent administration. Drug distribution in intravitreal injections is non-uniform due to injections into the vitreous humor.

Question 5

Describe the significance of molecular size and particle size in ocular drug delivery. How do these factors impact the effectiveness of drug delivery through eye drops and suspensions?

Answer 5

Molecular size (< 500 daltons) and particle size (< 10 μm) play a crucial role in ocular drug delivery. These factors influence drug absorption and distribution, affecting the effectiveness of delivery through eye drops and suspensions.

Question 6

How does the periocular route of drug delivery differ from direct intravitreal injections in terms of drug diffusion and bioavailability in the eye? What are the key considerations for drug permeation in periocular injections?

Answer 6

The periocular route involves injections on the outer surface of the eye, allowing for drug diffusion across the sclera. It offers lower intraocular bioavailability compared to direct intravitreal injections due to delays in diffusion and systemic clearance.

Question 7

Describe the challenges and different routes of drug delivery into ocular tissues. How do systemic and oral administrations differ in treating ocular diseases?

Answer 7

The challenges in ocular drug delivery include selecting the appropriate route based on the target tissue. Systemic administration faces barriers like the blood-aqueous and blood-retinal barriers. Oral administration, though patient-friendly, has limited accessibility to ocular tissues, requiring high dosages and risking systemic side effects.

Question 8

Define the static ocular barriers such as cornea and sclera. How do their characteristics differ in terms of structure and permeability?

Answer 8

The cornea, the eye’s outermost layer, is non-vascular, transparent, and negatively charged. It acts as a barrier for foreign substances. In contrast, the sclera is the tough, white outer part of the eye, providing structural support. It is more permeable than the cornea due to its matrix of mucopolysaccharides and collagen.

Question 9

Explain the physicochemical properties that influence drug permeation in the cornea. How do factors like lipophilicity, solubility, and molecular size affect drug delivery through the cornea?

Answer 9

Physicochemical properties like lipophilicity, solubility, molecular size, and degree of ionization impact drug permeation in the cornea. These properties determine the route and rate of drug permeation through the cornea, affecting the efficacy of ocular drug delivery.

Question 10

Describe the characteristics of the cornea in terms of size, transparency, and function as a barrier. How does the cornea’s structure contribute to its role in protecting the eye from foreign substances?

Answer 10

The cornea is approximately 11.7 mm in diameter, optically transparent, and 0.5 to 0.7 mm thick. It is non-vascular and negatively charged, providing a mechanical and chemical barrier against foreign substances. Its physicochemical properties and structure influence the permeation of drugs.

Question 11

Explain the role of the sclera in the eye and how it differs from the cornea in terms of structure and function. Why is the sclera considered more permeable than the cornea for drug delivery?

Answer 11

The sclera is the tough, white outer layer of the eye that provides structural support. It covers 80% of the eye’s surface and is thicker at the back. Unlike the cornea, the sclera is more permeable due to its matrix of mucopolysaccharides and collagen, allowing drug diffusion through ‘holes’ in the matrix.

Question 12

Describe the components and functions of the tear film in the eye.

Answer 12

The tear film in the eye consists of an external lipid layer, a middle aqueous layer, and an adherent mucous layer. It acts to remove material from the eye’s surface and serves as the first pre-corneal barrier for drug delivery.

Question 13

What are the characteristics and functions of the conjunctiva in relation to the eye?

Answer 13

The conjunctiva, located at the sides of the eye, helps in the formation and maintenance of the precorneal tear film. It has a large surface area, joins onto the cornea and eyelids, and its tight junctions act as a barrier for drug penetration.

Question 14

Define the vitreous humor and its role in the eye.

Answer 14

The vitreous humor fills about 80% of the eye between the lens and retina. It is optically clear, supports the shape of the retina and lens, and has a gel-like structure composed of water, collagen, and hyaluronate.

Question 15

How is the retina positioned in the eye and what is the significance of the blood-retinal barrier (BRB)?

Answer 15

The retina is located at the back of the eye, being very delicate and well perfused. The blood-retinal barrier restricts drug transport from the blood into the retina, allowing drugs to enter the choroid but limiting further entry into the retina.

Question 16

Discuss the pH values, thickness, and secretion rate of tears in the eye.

Answer 16

Tears in the eye have pH values ranging between 7.3 and 7.7, with a thickness of approximately 7 μm. They are secreted at a rate of 0.5–2.2 mL/min and play a crucial role in removing material from the eye’s surface.

Question 17

Describe the advantages of ocular implants as a drug delivery system over traditional methods for administering drugs to the eye.

Answer 17

Ocular implants offer benefits such as delivering constant therapeutic levels directly to the site of action, bypassing the blood-brain barrier, allowing release rates below toxic levels that can be adjusted, and achieving higher drug concentrations without systemic side effects.

Question 18

How do micro-electromechanical intraocular drug delivery devices work, and what advantages do they offer in drug delivery to the eye?

Answer 18

Micro-electromechanical intraocular drug delivery devices are small devices that can release drugs directly into the eye. They offer advantages such as precise drug delivery, reduced side effects, and improved patient compliance.

Question 19

Define iontophoresis and microneedles in the context of drug delivery to the eye, and explain their role in enhancing drug delivery efficiency.

Answer 19

Iontophoresis is a technique that uses an electric current to enhance the penetration of drugs into the eye. Microneedles are tiny needles that can deliver drugs into the eye more effectively than traditional methods, improving drug delivery efficiency.

Question 20

What are the different types of drug delivery systems used for the anterior segment of the eye, and how do they function in delivering drugs effectively?

Answer 20

Drug delivery systems for the anterior segment of the eye include eye-drops, subconjunctival/episcleral implants, punctal plugs, and contact lenses. They work by ensuring targeted drug delivery to the front part of the eye for effective treatment.

Question 21

Describe the role of non-biodegradable implants in ocular drug delivery, and provide examples of such devices used for sustained drug release in the eye.

Answer 21

Non-biodegradable implants are reservoir-type devices that slowly release drugs into the eye over time. Examples include Ocusert, Prosert, Illuvien, Vitrasert, and Retisert, which are used for sustained drug delivery in ocular conditions.

Question 22

Describe the different types of ocular implants and their respective uses in treating eye diseases.

Answer 22

Ocular implants can be subconjunctival for anterior-segment diseases, intrascleral/transcleral for either, and intravitreal/suprachoroidal for posterior-segment diseases.

Question 23

How does the OcusertTM system work in the treatment of glaucoma, specifically in relation to pilocarpine administration?

Answer 23

The OcusertTM system is a membrane-controlled reservoir system that releases pilocarpine at a constant rate for one week. Pilocarpine increases aqueous humor outflow, reducing intraocular pressure when administered 4-6 times daily.

Question 24

Define Membrane Permeation-Controlled Drug Delivery using the OcusertTM system as an example.

Answer 24

Membrane Permeation-Controlled Drug Delivery involves encapsulating a drug reservoir within polymeric membranes to control drug release. The OcusertTM system uses synthetic membranes to maintain a constant release rate of pilocarpine.

Question 25

Describe the composition and function of the barrier membrane in the OcusertTM system for controlled drug delivery.

Answer 25

The barrier membrane in the OcusertTM system is made of Ethylene/Vinylacetate copolymer, permeable to water and drug solution. It allows water to dissolve the drug in the core, maintaining a constant release rate through diffusion.

Question 26

How does the driving force for drug movement work in the OcusertTM system, and what maintains the constant release rate of the drug?

Answer 26

The driving force for drug movement is diffusion from a higher to lower concentration in the fluid. The constant release rate is maintained by the excess drug in the reservoir, forming a saturated solution that continues to release drug through the membrane.

Question 27

Explain the concept of zero-order kinetics release in the OcusertTM ocular therapeutic system.

Answer 27

Zero-order kinetics release in the OcusertTM system refers to a constant drug release rate independent of drug concentration. This is achieved by the controlled permeation of drug through the polymeric membrane, ensuring a consistent therapeutic effect over time.

Question 28

Describe the Pilo-20 and Pilo-40 ocular therapeutic systems in terms of drug release rate, total drug content, and drug remaining after one week.

Answer 28

The Pilo-20 system releases 20 μg/hr of pilocarpine for 7 days with a total of 3.4mg, leaving 32% after a week. The Pilo-40 system releases 40 μg/hr for 7 days with 6.7mg total, leaving 40% after a week.

Question 29

How does the OcusertTM System improve the delivery of pilocarpine compared to traditional eye drops?

Answer 29

The OcusertTM System reduces the number of instillations by delivering pilocarpine at 20 μg/hr, equivalent to a 2% eye drop solution instilled four times daily. This leads to more efficient use of the therapeutic agent.

Question 30

Define the Vitrasert® Implant and its purpose in medical treatment.

Answer 30

The Vitrasert® Implant is the world’s first intraocular drug delivery implant used to treat AIDS-related Cytomegalovirus retinitis. It is a reservoir implant made of non-biodegradable materials that can deliver continuous drug amounts for months to years.

Question 31

Describe the composition and function of reservoir implants like Vitrasert® in drug delivery.

Answer 31

Reservoir implants like Vitrasert® consist of a pelleted drug core surrounded by nonreactive substances such as silicon, EVA, or PVA. They are non-biodegradable and can deliver controlled amounts of drug over extended periods.

Question 32

How is the Vitrasert® Implant surgically implanted and what is its release mechanism?

Answer 32

The Vitrasert® Implant is surgically placed into the vitreous through the pars plana and attached to the sclera with a suture. It releases a specific dose of 4.5mg slowly over months to years.

Question 33

What are some complications associated with the Vitrasert® Implant in humans?

Answer 33

Complications of the Vitrasert® Implant in humans may include vitreous hemorrhage, retinal detachment, and endophthalmitis. These risks should be considered before implantation.

Question 34

Describe the Retisert® intraocular drug delivery implant, including its technology, purpose, duration, cost, and impact.

Answer 34

Retisert® is the world’s 2nd intraocular drug delivery implant utilizing Core Vitrasert Technology. It is designed for non-infectious posterior uveitis, delivering for 30 months at a cost of $18,000 per implant. While successful in preventing blindness, it has drawbacks like raised IOP and risk of cataracts.

Question 35

Explain the features and limitations of the Iluvien® intraocular drug delivery implant for Diabetic Macular Edema.

Answer 35

Iluvien® is the world’s 4th intraocular drug delivery implant using a non-bioerodible PLGA matrix delivered via a 25G needle for 36 months at $8,000 - $9,000 per implant. Despite its usefulness, it has drawbacks like large incisions, need for re-implantation, and serious side effects requiring expert ophthalmologists.

Question 36

What are the differences between Retisert® and Iluvien® intraocular drug delivery implants in terms of technology, purpose, duration, and cost?

Answer 36

Retisert® is designed for non-infectious posterior uveitis, delivering for 30 months at $18,000 per implant, while Iluvien® targets Diabetic Macular Edema, delivering for 36 months at $8,000 - $9,000 per implant. Retisert® uses Core Vitrasert Technology, whereas Iluvien® uses a non-bioerodible PLGA matrix.

Question 37

Discuss the advantages and disadvantages of using intraocular drug delivery implants like Retisert® and Iluvien® for treating eye conditions.

Answer 37

Intraocular drug delivery implants like Retisert® and Iluvien® offer long-term drug release, preventing blindness in conditions like uveitis and macular edema. However, they come with drawbacks such as invasive procedures, ocular side effects like cataracts, and the need for expert administration and post-operative care.

Question 38

How do Retisert® and Iluvien® intraocular drug delivery implants impact the field of retina technologies and eye health care?

Answer 38

Retisert® and Iluvien® have revolutionized the treatment of eye conditions by providing sustained drug delivery directly to the affected area, preventing blindness and improving patient outcomes. However, their invasive nature and potential side effects highlight the need for continuous innovation in retina technologies and eye health care.

Question 39

Describe Lacrisert and its role in treating dry eye symptoms.

Answer 39

Lacrisert is a sterile, rod-shaped ophthalmic insert made of hydroxypropyl cellulose. It stabilizes tear film, improves dry eye symptoms like discomfort, burning, and light sensitivity. It is administered daily and more effective than artificial tears.

Question 40

How does Lacrisert differ from topical artificial tears in treating dry eye symptoms?

Answer 40

Lacrisert, a biodegradable insert made of hydroxypropyl cellulose, provides sustained release of HPC to stabilize tear film. It is administered once daily and shown to be more effective than using artificial tears four times a day.

Question 41

Define Ozurdex and its use in treating macular edema following retinal vein occlusion.

Answer 41

Ozurdex is a biodegradable implant injected into the eye to release dexamethasone over six months. It is used to treat macular edema after branch or central retinal vein occlusion.

Question 42

Describe the composition and mechanism of action of Ozurdex in treating macular edema.

Answer 42

Ozurdex is composed of a PLGA matrix that degrades to release dexamethasone over six months. The sustained release of dexamethasone helps in treating macular edema following retinal vein occlusion.

Question 43

How does the cost of Ozurdex compare to other treatments for macular edema?

Answer 43

Ozurdex is a costly treatment at £1,665 per implant, with a maximum annual cost of £6,600 per patient. This cost includes the implant and administration expenses. Worldwide sales of Ozurdex were $56.5 million in 2011.

Question 44

Describe Surodex and its role in providing sustained drug release.

Answer 44

Surodex is a rod-shaped biodegradable matrix implant containing dexamethasone and PLGA with HPMC. It releases drugs at a constant rate over 7-10 days, providing sustained drug release for eye conditions.