drug delivery device unfolded to treat diabetes- related diabetic retinopathy

1. DRUG DELIVERY DEVICE UNFOLDED TO
TREAT DIABETES- RELATED DIABETIC
RETINOPATHY
K .TEJA KUMAR REDDY
13GD1R0023
IV-1 B.PHARMACY
Under the guidance of
MRS.SUSHMA MAM
Dept of Pharmaceutics

2. 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)

3. 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.

4. 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.

5. 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.

6. COMPARISON OF TYPE 1 AND TYPE 2

7. 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.

8. 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

9. 4. PATHOPHYSIOLOGY OF TYPE1 AND TYPE 2
TYPE 1 DIABETES TYPE 2 DIABETES

10. 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.

11. 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

12. 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.

13. 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

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 13.MICRO ELECTROMECHANICAL SYSTEM

22. 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.

23. 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.

24. 16. REFERENCES
1. Text book of Gerarad j .Tortora, principles of anatomy and physiology,
second edition, chapter 17,page No 579-583
2. 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 9.10
4. 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.k
6 .www.diabetes.orgu.k