Nanotherapy Offers Innovative Approaches to Diabetic Retinopathy

Commentary
Article

Preclinical studies and clinical trials have shown that both corticosteroids and VEGF inhibitors can be delivered as nanoparticles.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia. Prolonged hyperglycemia can lead to various chronic complications, including nephropathy, cardiomyopathy, neuropathy, and retinopathy. The International Diabetes Federation predicted that the number of individuals with DM was 463 million in 2019, and they anticipate this number to rise to 700 million by 2045.1 Diabetic retinopathy (DR), the most common and distinct complication of DM, is one of the primary causes of preventable blindness in working-age adults.2-6

The pathways contributing to the pathogenesis of DR include increased oxidative stress, resulting in elevated vascular endothelial growth factor (VEGF) secretion leading to angiogenesis and vascular permeability; increased oxidative stress leading to leukostasis and subsequent vascular occlusion; and increased glutamate levels leading to neurodegeneration.7

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Currently, the most successful approach for treating DR involves managing blood glucose levels. Advanced cases of this condition may require treatments like laser therapy, anti-VEGF therapy, steroids, or vitrectomy. Laser photocoagulation is used to enhance retinal circulation in patients with microcirculation alterations of the ocular fundus. For individuals with macular edema, anti-VEGF drugs are typically administered to alleviate macular edema and improve vision. In the most severe cases, such as fundus hemorrhage or proliferative vitreoretinopathy, vitrectomy is performed.8

Despite these treatments, many DR patients still experience vision loss and potential side effects. Considering the limited effectiveness of conventional drugs due to low bioavailability and potential side effects, and the inherent risks of major surgery, nanotechnology has been increasingly integrated into the field of medicine, offering innovative approaches to DR treatment.8

Nanotechnology involves the applications and characteristics of materials with dimensions ranging from 0.1 to 100 nm. As nanotechnology has rapidly advanced, it has found extensive applications in medicine and various other disciplines and fields.9,10 Due to its small molecular size and multiple functions, nanotechnology has also been integrated into modern drug research, providing solutions to the challenges experienced in conventional treatments.11,12 Nanodrugs can be specifically designed to transport medications, with reduced or even eliminated side effects. Additionally, they can achieve sustained release, prolonging the action time of drugs, enhancing the stability of drugs, simplifying drug storage, and establishing new drug delivery routes.

The use of nanoparticles is a novel therapeutic strategy for DR, and various nanoparticles have been studied. Loading drugs into nanoparticles could overcome some limitations, including enzymatic and chemical degradation, reduced half-life, low solubility in solvents, high doses required to exhibit therapeutic effects, and high toxicity. The main advantages of nanotechnology include small diameter, high penetrability through the blood-retina barrier, good biocompatibility, and reduced drug degradation in the body to achieve sustained release.2 The most commonly used nanoparticles to target the posterior segment of the eye include nanostructured lipid carriers, polymeric nanoparticles, solid lipid nanoparticles, cationic nanoemulsions, dendrimers, liposomes, and gold nanoparticles.13

Widely studied medications for diabetic retinopathy that can be delivered as nanoparticles include corticosteroids and antiangiogenic factors. Corticosteroids such as triamcinolone acetonide, dexamethasone, and fluocinolone acetonide reduce vascular permeability, prevent the breakdown of the blood-retinal barrier, down-regulate VEGF expression and/or production, and inhibit matrix metalloproteinases.14,15 Recombinant humanized antibodies showing activity against all isoforms of VEGF-A, such as bevacizumab, ranibizumab, and pegaptanib, have demonstrated efficacy in the treatment of diabetic retinopathy, diabetic macular edema, and iris neovascularization.16

Preclinical studies and clinical trials have shown that both corticosteroidsand VEGF inhibitors can be delivered as nanoparticles, and they appear to be a promising alternative to conventional systems, which are generally associated with very low bioavailability (5% to 10%) of the administered drugs.17-29

References

1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas. Diabetes research and clinical practice. 2019 Nov 1;157:107843.

2. Khalil H. Diabetes microvascular complications—A clinical update. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2017 Nov 1;11:S133-9.

3. Cheung N, Mitchell P, Wong T.Y. Diabetic retinopathy. Lancet. 2010 376: 124-136.

4. Fong DS, Aiello L, Gardner TW, King GL, et al. Blankenship G, CavalleranoJD, Ferris FL. Retinopathy in diabetes. Diabetes Care. 2004; 27: S84-S87.

5. Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Survey of Ophthalmology. 2012; 57: 347-370.

6. Leasher JL, Bourne RR, Flaxman SR, Jonas JB, Keeffe J, Naidoo K, Pesudovs K, Price H, White RA, Wong TY, Resnikoff S. Global estimates on the number of people blind or visually impaired by diabetic retinopathy: a meta-analysis from 1990 to 2010. Diabetes Care. 2016; 39: 1643-1649.

7. Pusparajah P, Lee LH, Abdul Kadir K. Molecular markers of diabetic retinopathy: potential screening tool of the future?. Frontiers in physiology. 2016 Jun 1;7:200.

8. Liu Y,Wu N. Progress of nanotechnology in diabetic retinopathy treatment. International journal of nanomedicine. 2021, 1391-1403.

9. Levin EM, Bud'Ko SL, Mao JD, Huang Y, Schmidt-Rohr K. Effect of magnetic particles on NMR spectra of Murchison meteorite organic matter and a polymer-based model system. Solid State Nuclear Magnetic Resonance. 2007, 63–71, 2007.

10. Gong R, Chen G. Preparation and application of functionalized nano drug carriers. Saudi Pharmaceutical Journal. 2016; pp. 254–257.

11. Zhang X, Yang C, Zhou J, Huo M. Somatostatin receptor-mediated tumor-targeting nanocarriers based on octreotide-PEG conjugated nanographene oxide for combined chemo and photothermal therapy. Small. 2016; pp. 3578–3590, 2016.

12. Choi BH, Lee HH, Jin S, Chun S, Kim SH. Characterization of the optical properties of silver nanoparticle films. Nanotechnology. 2007; p. 075706, 2007.

13. Fangueiro JF, Silva AM, Garcia ML, Souto EB. Current nanotechnology approaches for the treatment and management of diabetic retinopathy. European Journal of Pharmaceutics and Biopharmaceutics. 2015 Sep 1;95:307-22.

14. Rechtman E, Harris A, Garzozi HJ, Ciulla TA. Pharmacologic therapies for diabetic retinopathy and diabetic macular edema. Clinical ophthalmology. 2007 Dec 1;1(4):383-91.

15. Bhavsar AR. Diabetic retinopathy: the latest in current management. Retina. 2006 Jul 1;26(6):S71-9.

16. Mason III JO, Nixon PA, White MF. Intravitreal injection of bevacizumab (Avastin) as adjunctive treatment of proliferative diabetic retinopathy. American journal of ophthalmology. 2006 Oct 1;142(4):685-8.

17. Araújo J, Garcia ML, Mallandrich M, Souto EB, Calpena AC. Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): in vitro and ex vivo studies. Nanomedicine: Nanotechnology, Biology and Medicine. 2012 Aug 1;8(6):1034-41.

18. Araújo J, Nikolic S, Egea MA, Souto EB, Garcia ML. Nanostructured lipid carriers for triamcinolone acetonide delivery to the posterior segment of the eye. Colloids and Surfaces B: Biointerfaces. 2011 Nov 1;88(1):150-7.

19. Kadam RS, Tyagi P, Edelhauser HF, Kompella UB. RETRACTED: Influence of choroidal neovascularization and biodegradable polymeric particle size on transscleral sustained delivery of triamcinolone acetonide.

20. Suen WL, Chau Y. Specific uptake of folate-decorated triamcinolone-encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity. Journal of controlled release. 2013 Apr 10;167(1):21-8.

21. Herrero-Vanrell R, Cardillo JA, Kuppermann BD. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema. Clinical Ophthalmology. 2011 Feb 1:139-46.

22. Gómez-Gaete C, Tsapis N, Besnard M, Bochot A, Fattal E. Encapsulation of dexamethasone into biodegradable polymeric nanoparticles. International journal of pharmaceutics. 2007 Mar 1;331(2):153-9.

23. Driot JY, Novack GD, Rittenhouse KD, Milazzo C, Pearson AP. Ocular pharmacokinetics of fluocinolone acetonide after Retisert™ intravitreal implantation in rabbits over a 1-year period. Journal of Ocular Pharmacology and Therapeutics. 2004 Jun 1;20(3):269-75.

24. Pearson PA, Comstock TL, Ip M, Callanan D, Morse LS, Ashton P, Levy B, Mann ES, Eliott D. Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial. Ophthalmology. 2011 Aug 1;118(8):1580-7.

25. Solaiman KA, Diab MM, Dabour SA. Repeated intravitreal bevacizumab injection with and without macular grid photocoagulation for treatment of diffuse diabetic macular edema. Retina. 2013 Sep 1;33(8):1623-9.

26. Jorge R, Costa RA, Calucci D, Cintra LP, Scott IU. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina. 2006 Nov 1;26(9):1006-13.

27. Cintra LP, Costa RA, Ribeiro JA, Calucci D, Scott IU, Messias A, Jorge R, Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study): 1-year results, Retina. 2013 33: 1109–1116.

28. Varshochian R, Jeddi-Tehrani M, Mahmoudi AR, Khoshayand MR, Atyabi F, Sabzevari A, Esfahani MR, Dinarvand R. The protective effect of albumin on bevacizumab activity and stability in PLGA nanoparticles intended for retinal and choroidal neovascularization treatments. European Journal of Pharmaceutical Sciences. 2013 Nov 20;50(3-4):341-52.

29. Sanford M. Fluocinolone acetonide intravitreal implant (Iluvien®) in diabetic macular oedema. Drugs. 2013 Feb;73(2):187-93.

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