DRUG DELIVERY DEVICE UNFOLDED TO TREAT DIABETES- RELATED DIABETIC RETINOPATHY

K .TEJA KUMAR REDDY13GD1R0023IV-1 B.PHARMACY

Under the guidance of MRS.SUSHMA MAMDept of Pharmaceutics

DRUG DELIVERY DEVICE UNFOLDED TO TREAT DIABETES- RELATED DIABETIC RETINOPATHY

INTRODUCTION

Diabetic retinopathy is a micro-vascular complication that occurs due to

changes in the retinal circulation and is composed of a characteristic

group of lesions found in the retina of individuals having diabetes

mellitus for several years.

Diabetic retinopathy is increasingly becoming a major cause of blindness

throughout the world in the age group of 20–60 years.

Diabetic retinopathy is classified into two types:

Non-proliferative diabetic retinopathy (NPDR)

Proliferative diabetic retinopathy(PDR)

2. STRUCTURE OF EYE

The right side of retina of each eye transfers through the optic nerve the “right part” of the image to the right side of the brain, the left retinal side operates in the similar mode.

3.FUNCTIONS OF EYE

They convert light into electrical signals which are deciphered by the brain

into images. Properly working healthy eyes are able to perform the

following functions.

They help us view our surroundings.

Our eyes enable us to see colors. Certain organisms, such as dogs, cannot

see colors and, so, their world is black and white.

Eyes help us see near as well as distant objects.

4.DIABETES Diabetes mellitus is a group of metabolic diseases characterized by

elevated blood glucose levels (hyperglycemia) resulting from defects in

insulin secretion, insulin action or both.

Insulin is a hormone manufactured by the beta cells of the pancreas,

which is required to utilize glucose from digested food as an energy

source. Chronic hyperglycemia is associated with microvascular and

macrovascular complications that can lead to visual impairment,

blindness, kidney disease, nerve damage, amputations, heart disease, and

stroke.

COMPARISON OF TYPE 1 AND TYPE 2

5. ETIOLOGY /CONTRIBUTING FACTORS

Type 1 Diabetes

Caused by the immune destruction of the beta cells of the pancreas.

Insulin secretion gradually diminishes

May present at any age, but most common in childhood and adolesce

Insulin by injection is necessary for survival.

Type 2 Diabetes

Caused by insulin resistance in the liver and skeletal muscle, increased

glucose production in the liver, over production of free fatty acids by fat cells

and relative insulin deficiency.

CONTD.

Insulin secretion decreases with gradual beta cell failure

Reductions in blood glucose levels often can be achieved with changes in food intake and physical activity patterns.

Contributing factors: Obesity Age (onset of puberty is associated with increased insulin

resistance) Lack of physical activity Genetic predisposition Racial/ethnic background (African American, Native

American, Hispanic and Asian/Pacific Islander)Conditions associated with insulin resistance, (e.g., polycystic ovary syndrome)

4. PATHOPHYSIOLOGY OF TYPE1 AND TYPE 2

TYPE 1 DIABETES TYPE 2 DIABETES

5.WHAT IS DIABETIC EYE DISEASE?

Diabetic eye disease is a group of eye conditions that can affect people with diabetes.

Diabetic retinopathy affects blood vessels in the light-sensitive tissue called the retina that lines the back of the eye. It is the most common cause of vision loss among people with diabetes and the leading cause of vision impairment among working-age adults.

Diabetic macular edema (DME). A consequence of diabetic retinopathy, DME is swelling in an area of the retina called the macula.

6.DIABETIC EYE DISEASE Diabetic eye disease also includes cataract and glaucoma:

Cataract: is a clouding of the eye’s lens. Adults with diabetes are 2-5

times more likely than those without diabetes to develop cataract. Cataract

also tends to develop at an earlier age in people with diabetes.

Glaucoma is a group of diseases that damage the eye’s optic nerve—the

bundle of nerve fibres that connects the eye to the brain. Some types of

glaucoma are associated with elevated pressure inside the eye. In adults,

diabetes nearly doubles the risk of glaucoma.

All forms of diabetic eye disease have the potential to cause severe vision

loss and blindness

7. DIABETIC RETINOPATHY Chronically high blood sugar from diabetes is associated

with damage to the tiny blood vessels in the retina, leading to diabetic retinopathy.

The retina detects light and converts it to signals sent through the optic nerve to the brain.

Diabetic retinopathy can cause blood vessels in the retina to leak fluid or haemorrhage (bleed), distorting vision. In its most advanced stage, new abnormal blood vessels proliferate (increase in number) on the surface of the retina, which can lead to scarring and cell loss in the retina.

DIABETIC RETINOPATHY MAY PROGRESS THROUGH FOUR STAGES:

1.Mild non-proliferative retinopathy. Small areas of balloon-like swelling in the retina’s tiny blood vessels, called micro aneurysms, occur at this earliest stage of the disease. These micro aneurysms may leak fluid into the retina.

2.Moderate non-proliferative retinopathy. As the disease progresses, blood vessels that nourish the retina may swell and distort. They may also lose their ability to transport blood. Both conditions cause characteristic changes to the appearance of the retina and may contribute to DME

3.Severe non-proliferative retinopathy. Many more blood vessels are blocked, depriving blood supply to areas of the retina. These areas secrete growth factors that signal the retina to grow new blood vessels.

4.Proliferative diabetic retinopathy (PDR). At this advanced stage, growth factors secreted by the retina trigger the proliferation of new blood vessels, which grow along the inside surface of the retina and into the vitreous gel, the fluid that fills the eye. The new blood vessels are fragile, which makes them more likely to leak and bleed. Accompanying scar tissue can contract and cause retinal detachment. Retinal detachment can lead to permanent vision loss.

8. DIABETIC MACULAR EDEMA (DME)

DME is the build-up of fluid (edema) in a region of the retina called the macula. The macula is important for the sharp, straight-ahead vision that is used for reading, recognizing faces, and driving. DME is the most common cause of vision loss among people with diabetic retinopathy. About half of all people with diabetic retinopathy will develop DME. DME can happen at any stage of the disease.

The early stages of diabetic retinopathy usually have no symptoms. The disease often progresses unnoticed until it affects vision. Bleeding from abnormal retinal blood vessels can cause the appearance

of “floating” spots. These spots sometimes clear on their own . But without prompt treatment, bleeding often recurs, increasing the risk of permanent vision loss. If DME occurs, it can cause blurred vision

DIABETIC RETINOPATHY AND DME ARE DETECTED DURING A COMPREHENSIVE DILATED EYE EXAM THAT INCLUDES:

Visual acuity testing. This eye chart test measures a person’s ability to see at various distances.

Tonometry. This test measures pressure inside the eye.

Pupil dilation: Drops placed on the eye’s surface dilate (widen) the pupil, allowing a physician to examine the retina and optic nerve

Optical coherence tomography (OCT). This technique is similar to ultrasound but uses light waves instead of sound waves to capture images of tissues inside the body.

OCT provides detailed images of tissues that can be penetrated by light, such as the eye.

A COMPREHENSIVE DILATED EYE EXAM ALLOWS THE DOCTOR TO CHECK THE RETINA FOR: Changes to blood vessels Leaking blood vessels or warning signs of leaky blood

vessels, such as fatty deposits Swelling of the macula (DME) Changes in the lens Damage to nerve tissue If DME or severe diabetic retinopathy is suspected,

a fluorescein angiogram may be used to look for damaged or leaky blood vessels. In this test, a fluorescent dye is injected into the bloodstream, often into an arm vein.

Pictures of the retinal blood vessels are taken as the dye reaches the eye.

9. PREVENTION However, early detection and treatment can reduce the risk of

blindness by 95 percent. people with diabetes should get a comprehensive dilated eye exam at

least once a year. People with diabetic retinopathy may need eye exams more

frequently. Women with diabetes who become pregnant should have a

comprehensive dilated eye exam as soon as possible. Additional exams during pregnancy may be needed.

Diabetes Control and Complications Trial (DCCT) study participants who kept their blood glucose level as close to normal as possible were significantly less likely than those without optimal glucose control to develop diabetic retinopathy, as well as kidney and nerve diseases.

Other trials have shown that controlling elevated blood pressure and cholesterol can reduce the risk of vision loss among people with diabetes.

10. TREATMENT

Treatment for diabetic retinopathy is often delayed until it starts to progress to PDR, or when DME occurs.

Comprehensive dilated eye exams are needed more frequently as diabetic retinopathy becomes more severe.

People with severe non proliferative diabetic retinopathy have a high risk of developing PDR and may need a comprehensive dilated eye exam as often as every 2 to 4 months.

11.BIOCHEMICAL PATHWAYS OF DIABETIC RETINOPATHY

The contributors in the development of diabetic retinopathy are increased polypol pathway ,activation of protein kinase c (pkc) ,increased expression of growth factors such as vascular endothelial growth factors such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1), haemodynamic changes, accelerated formation of advanced glycation end products (AGEs), oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and subclinical inflammation and capillary occlusion.

Among the all mechanisms, increased production of growth factors, hemodynamic changes and protein kinase -c are responsible for the Angiogenesis.

12.RECENT ADVANCEMENT

The University of British Columbia recently reported about the development of MEMS (Microelectromechanical system) device.

It contains a micro reservoir sealed by polydimethylsiloxane membrane and is capable of releasing drug on demand.

By applying the magnetic field, the PDMS membrane with laser-drilled aperture deforms causing the discharge of Docetaxel from the reservoir.

  The biological activity of the drug released was investigated by

using two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells and cell apoptosis is seen in the cytotoxic assay.

The device maintained its pharmacological efficacy for two months.

13.MICRO ELECTROMECHANICAL SYSTEM

14. MECHANISM OF DOCETAXEL IN TREATING DIABETIC RETINOPATHY

Docetaxel binds to tubulin, the protein component of microtubules, and simultaneously promotes assembly and inhibits disassembly of them. Stabilization of microtubules leads to inhibition of cell division (mitosis) and cell proliferation, resulting in cell death.

15. CONCLUSION

The newly developed MEMS (Microelectromechanical system) device contains a micro reservoir sealed by a polydimethylsiloxane membrane with a laser drilled aperture

Thus Docetaxel improves quality of life of patients suffering with diabetic retinopathy besides treating the ovarian, prostate, liver, renal, gastric ,head and neck cancers.

16. REFERENCES1. Text book of Gerarad j .Tortora, principles of anatomy and physiology,

second edition, chapter 17,page No 579-5832. Text book of anatomy and physiology in health and illness by Ross and

Wilson, tenth edition 2006, page No 23-204 3. Text book of Pathophysiology by Dr.N.L Bodhankar ninth edition 2014,

page N.o 9.8 to 9.104. Shraddha jalan, A.A tayade, in the journal of international journal of

advance research in computer science and management studies, volume 3 ,issue 1, Jan 2015,page N.O 128-131

5. www.diabetic-retinopathy.screeningnhs.u.k6 .www.diabetes.orgu.k