INTRODUCTION:

Diabetes mellitus (DM) is a global disease that has already afflicted 382 million people and will afflict 559 million by 2035¹. Managing diabetes mellitus-related complications in addition to the basic disease is the major issue for researchers and health-care providers. Diabetes retinopathy, the most serious microvascular consequence, is more likely to occur in diabetic people².

Diabetic retinopathy (DR) causes blindness in persons aged 20 to 65 years. Nearly all type 1 diabetes patients and more than 60% of type 2 diabetes patients are at risk of developing diabetic retinopathy after ten years of diabetes³.

Diabetic retinopathy (DR) is a form of diabetes mellitus that causes vision loss and decreases patient quality of life. The biochemical and anatomic abnormalities that occur in DR are discussed in this study in order to better understand and control the creation of new therapeutic options. Innovative drug delivery systems based on nanoparticles (e.g., liposomes, dendrimers, cationic nano-emulsions, lipid and polymeric nanoparticles) are compared to current standard therapy, with the benefits of suggested nanomedicines for treating this ocular ailment highlighted. Despite the fact that the multifaceted nature of DR remains unknown, nanoparticle-based strategies are being used to increase drug delivery to the posterior area of the eye. Certain nanoparticles, on the other hand, appear to play a role in the development of DR symptoms (e.g., retinal neovascularization), which is being investigated further in the context of efficient ocular chronic disease treatment.^4,5,6.

Retina's Anatomy:

The retina is a single layer of tissue that contains nerve cells that transmit images to the optic nerve. The retina consists of the following components:^7,8,9

· Macula: A little area near the very centre of the retina. The macula is ideal for seeing little details on things right in front of you, such as the text in a book.

· Fovea: A little depression in the centre of the macula. The fovea (sometimes called fovea centralis) is the eye's sharpest focus point.

· Photoreceptor cells: Photoreceptor cells are nerve cells that allow the eye to detect light and colour.

· Cones: A cone is a type of photoreceptor cell that detects and processes red, blue, and green colours, allowing for full-colour vision. In the retina, there are around 6 million cones.

· Rods: A type of photoreceptor cell that senses light levels while also providing peripheral vision. There are around 120 million people in the world.

· Peripheral retina: The peripheral retina is the retinal tissue that extends beyond the macula. Nerves in the peripheral retina process peripheral vision.

Retinopathy in Diabetics:

Diabetic retinopathy (DR) is a microvascular disorder that leads to blindness as a result of long-term erection. It is the most common complication of diabetes in the Western world, and it leads to vision-threatening retinal degeneration, which causes severe vision loss in people of working age^4,10,11. Early detection and treatment are crucial in preventing diabetic retinopathy-related blindness.

CAUSES:

The little blood vessels that nourish your retina can become blocked as a result of too much sugar in your blood, cutting off your retina's blood supply. As a result, the eye attempts to create new blood vessels. These new blood vessels, however, may not develop properly and are prone to leaking^12,13.

There are two types of diabetic retinopathy:

Early Diabetic Retinopathy:

Nonproliferative diabetic retinopathy (NPDR) is a more common kind of diabetic retinopathy in which new blood vessels do not grow (proliferating)¹⁴ which contain figure-1.

When you have NPDR, the walls of the blood vessels in your retina degenerate. Small Thebulges protrude from the walls of the smaller vessels, leaking fluid and blood into the retina on occasion. Larger retinal vessels may dilate and become asymmetrical in size. NPDR can progress from mild to severe when more blood vessels get occluded.

Retinal blood vessel injury can cause edoema (fluid accumulation) in the macular area of the retina. If macular edoema causes vision loss, treatment is required to prevent permanent vision loss.

A B

Figure-1 a. Non-proliferative diaqbetic retinopathy b. Proliferative diabetic retinopathy

Advanced Diabetic Retinopathy:

Advanced diabetic retinopathy, also known as proliferative diabetic retinopathy, can develop from diabetic retinopathy. In this type, damaged blood vessels seal off, causing the retina to generate new, abnormal blood vessels which contain figure-1. These new blood vessels are delicate, and they could bleed into the clear, jellylike fluid that fills the centre of your eye (vitreous).

Due to scar tissue created by the creation of new blood vessels, the retina may eventually detach from the back of your eye. Pressure in the eyeball may build up if the new blood vessels obstruct the normal flow of fluid out of the eye. A build-up of fluid on the nerve that delivers images from your eye to your brain causes glaucoma (optic nerve).

Diabetic Retinopathy treatment through nanomedicine:

Nanomedicine has become the most popular therapeutic option in recent years. Its main purpose is to boost the efficacy and controllability of currently used drugs in the target tissue. Nanoparticles with a diameter of 1–1,000nm were used in this study. They prevent the biological environment from being deactivated by peptide and protein-based drugs. It enables controlled and extended drug release, improved bio usability and tissue targeting, and a decrease in pharmacological side effects. Drugs with therapeutic potential are encapsulated in nanoparticles or bound to their surfaces. The releasing characteristics of the nanoparticles used are determined by their biological features and the time it takes for them to break down. As a result of these features, drug aggregation, enzymatic and chemical degradation, and drug half-life are all reduced. There are seven different types of nanoparticles. Nanoparticles include polymeric nanoparticles, liposomes, PEG-coated liposomes, cationic nano emulsions, dendrimers, NLC [nano structured lipid carriers], and SLN [solid lipid nanoparticles]. Polymeric nanoparticles are made from two types of polymers: synthetic and natural. Chitosan, starch, alginate, and cellulose are natural polymers, while PHB [polyp-hydroxybutyrate], PLGA [polyurethane poly lactic-co-glycolic acid], PLA [polylactic acid], and PMMA [poly (methyl methacrylate)] are synthetic polymers¹⁰. Polymeric nanoparticles such as chitosan, polyvinyl alcohol, PLGA, PLA, and PMMA are frequently used in therapy. These polymers have been authorised by the Food and Drug Administration¹¹. In addition to drug administration, these polymers are used as tissue-engineered scaffolds, gene delivery, vaccine distribution, cancer diagnostics, and dental and bone material¹⁰. Lipid nanoparticles such as NLC, SLN, and liposomes are popular, and studies for ocular applications have been published¹³. Although polyamidoamine polymers are often used to make dendrimers, cationic nano emulsions can interact with the human ocular mucosa due to electrostatic forces in their structure¹⁵. Apart from all of these advantages, the most notable disadvantage of nanoparticles is that their production takes a long time and costs a lot of money. They also have difficulty in the workplace. Simultaneously, frequent applications and progressive release could cause pulmonary inflammation, cancer, and cardiovascular harm. The treatment cannot be halted at any time, and perfect tissue targeting is unlikely^16,17. The targeting and drug delivery system features of nanoparticles aroused attention to their potential application in ocular neovascularization, motivating to develop betamethasone sodium phosphate-loaded nanoparticles for ocular administration¹⁸. Two scientists investigated betamethasone-loaded chitosan–sodium alginate nanoparticles. They sought to make a nanoparticle-based eye drop that was successful in targeting the posterior area of the eye^19,20,21. Intravitreal injection of bevacizumab-chitosan nanoparticles reduces angiogenesis in diabetic rats by lowering VEGF expression in the DR, and bevacizumab-chitosan nanoparticles had a longer duration of effect^22,23. Intravitrealranibizumab nanoparticles based on chitosan have also been investigated²⁴. Topically administered nilvadipine nanoparticles to rats may prevent retinal impairment²⁵. The key property of SLN, aside from the fact that they are not biotoxic, is that they can be used as an ocular drug delivery method for tetrandrine²⁶. Cationic nanoparticles improve tissue targeting in the posterior area of the eye by prolonging drug retention in the ocular mucosa²⁷. In the eyes, a lipid carrier-loaded triamcinolone acetonide has antiangiogenicactivity¹³. Liposomal minocycline injection of the subconjunctiva was reported to be able to reach the posterior region of the eye in diabetic rats²⁸. In light of these findings, nanoparticle-related Diabetic Retinopathy and other disease therapeutic investigations appear promising, but more research is needed.

Recent Approaches for the Treatment of Diabetic Retinopathy Have Been Approved by The FDA:

Diabetic retinopathy treatment can be split into two categories: systemic and local ocular treatments. The two main therapy techniques for systemic treatment are blood sugar and blood pressure management. Both the DCCT (Diabetes Control and Complications Trial) and the UKPDS (United Kingdom Prospective Diabetes Study) discovered that stringent blood sugar control (HbA1c, 7%) reduced the risk of complications²⁹.

In the UKPDS, tight blood pressure management was demonstrated to result in a three-fold reduction in the development of retinopathy, a two-fold reduction in vision loss, and a three-fold reduction in the need for laser therapy in type 2 DR. According to the DCCT study, DR progression is proportional to triglyceride levels and inversely proportional to HDL levels³⁰. According to epidemiological and clinical research, hypertension, another systemic risk factor, is a modifiable risk factor for the development of DR. Every 10 mmHg increase in systemic systolic blood pressure increases the creation of DR by 10%, and the development of significantly proliferative DR increases by 15% at an early stage³¹. On a local level, laser photocoagulation, IVTA injection, intravitreal anti-anti VEGF medications, and intravitreal steroid implants are some of the latest DR treatments. Nanomedicine, stem cells, and other systemic therapeutic techniques were also considered³².

FUTURE PERSPECTIVES:

Long-term pharmaceutical release and less invasive administration should be addressed in future ocular delivery systems, while therapeutic effectiveness inside the intraocular space is preserved. Modern nanotechnology and tissue engineering should be used to generate long-acting medicinal molecules with good eye biocompatibility. As a result, no serious local or systemic side effects should be expected. Changes in molecule sizes and surfaces, as well as specialised retinal cell targeting, are also required for increased treatment efficiency (RPE and photoreceptors). Extensive and long-term examinations of ocular toxicity and biocompatibility, with an emphasis on immunological, biochemical, and ophthalmological variables, should be done in addition to undertaking consistent human trials following pre-clinical research³⁰.

CONCLUSION:

Diabetic retinopathy is a prevalent diabetes complication that will cause visual loss in millions of people in the coming decades. Current therapy options are extremely intrusive and come with a slew of negative side effects. By extending medication residence time in the eye and increasing drug pharmacokinetic qualities, the use of nanomedicine to modify pharmaceutical formulations could reduce the number of injections required to treat this illness. Furthermore, nanocarriers have the potential to broaden the range of DR treatments by improving the efficacy of biologics, notably proteins and RNA molecules. Understanding the natural features of some materials utilised to create nanoparticles in reducing neo-angiogenesis and the inflammatory process requires more research. Finally, some of the research presented here found that using nano formulations topically or systemically reduced the risk of DR. These findings potentially be a game-changer in the treatment of DR, but additional research is needed to fully comprehend nanoparticle trafficking via ocular biological barriers.

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest.

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Received on 18.05.2022 Modified on 15.12.2022

Research J. Pharm. and Tech 2023; 16(7):3507-3510.

DOI: 10.52711/0974-360X.2023.00579