Investigation of the Penetration Ability of InP/ZnSe/ZnS 650 Quantum Dots into the Anterior Chamber of the Eye by Topical Application. Experimental Study

In connection with the problem of formation of strains of pathogenic microflora resistant to antibacterial drugs, research on the use of nanoparticles, namely quantum dots, has been actively conducted recently. Quantum dots can be used as an anti-infective agent, a means for visualization of intraocular structures, drug delivery, as well as a means for electrical stimulation of the retina. Successful application of quantum dots as an anti-infective agent necessitates the study of their penetrating ability into the anterior chamber. The aim of the study was to experimentally investigate the penetration ability of InP/ZnSe/ZnS 650 QDs in the anterior chamber of the eye at topical application. The object of the study was InP/ZnSe/ZnS 650 quantum dots. The study was carried out on laboratory rabbits (#6), which were divided randomly in pairs into groups. In rabbits #1 and #2 the eyes remained intact, #3 and #4 — a bandage soft contact lens was placed on the cornea of the right eye, #5 and #6 the cornea of the right eye was de-epithelialized. All experimental rabbits during the day 6 times instillation of 10 % solution of InP/ZnSe/ZnS 650 quantum dots was performed, and at the end 0.2 ml of moisture was taken from the anterior chamber of the right eye. The left eyes in all individuals were the control group. Identification of quantum dots into the anterior chamber was performed using a highly sensitive spectrophotometer UV-3600 (Shimadzu). The experimental study of the ability of InP/ZnSe/ZnS 650 quantum dots at topical application to penetrate into the intraocular cavity by the claimed detection methods did not allow their detection in the anterior chamber moisture even in minimal concentration.

1. Maiti S, Paul S, Mondol R, Ray S, Sa B. Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: in vitro and in vivo evaluation. AAPS PharmSciTech. 2011 Jun;12(2):755–763. doi: 10.1208/s12249-011-9643-9.

2. Reimondez-Troitiño S, Csaba N, Alonso MJ, de la Fuente M. Nanotherapies for the treatment of ocular diseases. Eur J Pharm Biopharm. 2015 Sep;95(Pt B):279–293. doi: 10.1016/j.ejpb.2015.02.019.

3. Mantelli F, Argüeso P. Functions of ocular surface mucins in health and disease. Curr Opin Allergy Clin Immunol. 2008 Oct;8(5):477–483. doi: 10.1097/ACI.0b013e32830e6b04.

4. Agrahari V, Mandal A, Agrahari V, Trinh HM, Joseph M, Ray A, Hadji H, Mitra R, Pal D, Mitra AK. A comprehensive insight on ocular pharmacokinetics. Drug Deliv Transl Res. 2016 Dec;6(6):735–754. doi: 10.1007/s13346-016-0339-2.

5. Wels M, Roels D, Raemdonck K, De Smedt SC, Sauvage F. Challenges and strategies for the delivery of biologics to the cornea. J Control Release. 2021 May 10;333:560–578. doi: 10.1016/j.jconrel.2021.04.008.

6. Mark R. Prausnitz, Jeremy S. Noonan. Permeability of cornea, sclera, and conjunctiva: A literature analysis for drug delivery to the eye. Journal of Pharmaceutical Sciences. 1988;87(12):1479–1488, doi:10.1021/js9802594.

7. Weng J, Song X, Li L, Qian H, Chen K, Xu X, Cao C, Ren J. Highly luminescent CdTe quantum dots prepared in aqueous phase as an alternative fluorescent probe for cell imaging. Talanta. 2006 Sep 15;70(2):397–402. doi: 10.1016/j.talanta.2006.02.064.

8. Zhao P, He K, Han Y, Zhang Z, Yu M, Wang H, Huang Y, Nie Z, Yao S. Near-infrared dual-emission quantum dots-gold nanoclusters nanohybrid via co-template synthesis for ratiometric fluorescent detection and bioimaging of ascorbic acid in vitro and in vivo. Anal Chem. 2015 Oct 6;87(19):9998–10005. doi: 10.1021/acs.analchem.5b02614.

9. Li H, Li K, Dai Y, Xu X, Cao X, Zeng Q, He H, Pang L, Liang J, Chen X, Zhan Y. In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles. Nanomedicine. 2018 Aug;14(6):1867–1877. doi: 10.1016/j.nano.2018.04.018.

10. Khanal S, Millar TJ. Nanoscale phase dynamics of the normal tear film. Nanomedicine. 2010 Dec;6(6):707–713. doi: 10.1016/j.nano.2010.06.002.

11. Keller KE, Bradley JM, Vranka JA, Acott TS. Segmental versican expression in the trabecular meshwork and involvement in outflow facility. Invest Ophthalmol Vis Sci. 2011 Jul 7;52(8):5049–5057. doi: 10.1167/iovs.10-6948.

12. Ho JH, Ma WH, Tseng TC, Chen YF, Chen MH, Lee OK. Isolation and characterization of multi-potent stem cells from human orbital fat tissues. Tissue Eng Part A. 2011 Jan;17(1–2):255–266. doi: 10.1089/ten.TEA.2010.0106.

13. De Hoon I, Barras A, Swebocki T, Vanmeerhaeghe B, Bogaert B, Muntean C, Abderrahmani A, Boukherroub R, De Smedt S, Sauvage F, Szunerits S. Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties. ACS Appl Mater Interfaces. 2023;15(3):3760–3771. doi: 10.1021/acsami.2c18598.

14. Jian HJ, Wu RS, Lin TY, Li YJ, Lin HJ, Harroun SG, Lai JY, Huang CC. Super-Cationic Carbon Quantum Dots Synthesized from Spermidine as an Eye Drop Formulation for Topical Treatment of Bacterial Keratitis. ACS Nano. 2017;11(7):6703–6716. doi: 10.1021/acsnano.7b01023.

15. Shilovskikh OV, Ponomarev VO, Kazaykin VN, Tkachenko KA. Bacterial Keratitis. Part 2. Topical Aspects of Treatment. Ophthalmology in Russia. 2023;20(1):24–32 (In Russ.). https://doi.org/10.18008/1816-5095-2023-1-24-32.

16. Ponomarev VO, Kazaykin VN, Lizunov AV, Vokhmintsev AS, Vainshtein IA, Dezhurov SV, Marysheva VV. Evaluation of the Ophthalmotoxic Effect of Quantum Dots InP/ZnSe/ZnS 650 and Bioconjugates Based on Them in Terms of the Prospects for the Treatment of Resistant Endophthalmitis. Experimental Research. Part 2 (Stage 1). Ophthalmology in Russia. 2021;18(4):876–884 (In Russ.). doi: 10.18008/1816-5095-2021-4-876-884.

17. Zhang J, Wang J, Yan T, Peng Y, Xu D, Deng D. InP/ZnSe/ZnS quantum dots with strong dual emissions: visible excitonic emission and near-infrared surface defect emission and their application in in vitro and in vivo bioimaging. J. Mater. Chem. B. 2017;5(41):8152–8160. doi: 10.1039/c7tb02324c.

18. Cabrera-Aguas M, Khoo P, Watson SL. Infectious keratitis: A review. Clin Exp Ophthalmol. 2022 Jul;50(5):543–562. doi: 10.1111/ceo.14113

19. Ting DS, Shan Ho C, Deshmukh R, et al. Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Nature (Eye). 2021;35:1084–1101. doi: 10.1038/s41433-020-01339-3.

20. Siplivyj VA, Dronov AI, Kon EV, Evtushenko DV. Antibiotics and antibacterial therapy in surgery. Kiev: Ferz-TA; 2006, P. 94–99 (In Russ.).

21. Aramă V. Topical antibiotic therapy in eye infections — myths and certainties in the era of bacterial resistance to antibiotics. Rom J Ophthalmol. 2020 JulSep;64(3):245–260

22. Safonova TN, Novikov IA, Boev VI, Gladkova OV. Modification of therapeutic silicone-hydrogel soft contact lenses. RMJ Clinical Ophthalmology. 2016;16(3):117–120 (In Russ.).

23. ВVorontsova TN, Popov VYu, Tugeeva EE, Shaporova VYa. Minimum suppressive concentration of antibacterial drugs — an indicator of antibiotic therapy efficiency. Modern technologies in ophthalmology. 2014;4:26 (In Russ.).

24. Healy DP, Holland EJ, Nordlund ML, Dunn S, Chow C, Lindstrom RL, Hardten D, Davis E. Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration. Cornea. 2004 Apr;23(3):255–263. doi: 10.1097/00003226-200404000-00007.

25. Boiko EV, Fokina DV, Reituzov VA, Alekperov SI. The comparison of different drug delivery methods of levofloxacinin the anterior chamber. Ophthalmologi Reports. 2013;6(2):25–29 (In Russ.).

26. Gaisina GYa, Aznabaev MT, Azamatova GA, Mudarisova RH, Badykova LA, Sabirov OK. The study of moxifloxacin concentration in the aqueous humor of eye anterior chamber with different methods of its delivery. Bashkortostan medical journal. 2016;11(1):116–118 (In Russ.).

27. Cagini C, Piccinelli F, Lupidi M, Messina M, Cerquaglia A, Manes S, Fiore T, Pellegrino RM. Ocular penetration of topical antibiotics: study on the penetration of chloramphenicol, tobramycin and netilmicin into the anterior chamber after topical administration. Clin Exp Ophthalmol. 2013 Sep-Oct;41(7):644–647. doi: 10.1111/ceo.12087.

28. Egorov EA, Alekseev VN, Astahov YuS, Brzhevskiy VV, Brovkina AF, Dushin NV, Egorov AE, Egorova GB, Ermakova NA, Kochergin SA, Moshetova LK, Neroev VV, Nesterov AP, Polunin GS, Rybakova EG, Skatkov SA, Stavickaya TV, Tankovskiy VYe, Ustinova EI. Rationale for drug therapy in ophthalmology. A guidebook for medical practitioners. Moscow: Litterra Publ., 2004. 33 p. (In Russ.).

29. Shulgina NA, Dogadova LP, Melnikov VYa, Negoda VI. Aminoglycosides and their rational usage in inflammatory eye globe diseases. Literary review. RMJ Clinical Ophthalmology. 2012;1:36–38 (In Russ.).

30. Blondeau JM. New concepts in antimicrobial susceptibility testing: the mutant prevention concentration and mutant selection window approach. Vet Dermatol. 2009 Oct;20(5–6):383–396. doi: 10.1111/j.1365-3164.2009.00856.

31. Savchenko SS, Weinstein IA. Inhomogeneous Broadening of the Exciton Band in Optical Absorption Spectra of InP/ZnS Nanocrystals. Nanomaterials (Basel). 2019 May 9;9(5):716. doi: 10.3390/nano9050716.

32. Gaponenko SV. Optical Properties of Semiconductor Nanocrystals. Cambridge, UK: Cambridge University Press; 1998: 245. doi: 10.1017/CBO9780511524141.

33. Wu W, Aiello M, Zhou T, Berliner A, Banerjee P, Zhou S. In-situ immobilization of quantum dots in polysaccharide-based nanogels for integration of optical pH-sensing, tumor cell imaging, and drug delivery. Biomaterials. 2010 Apr;31(11):3023–3031. doi: 10.1016/j.biomaterials.2010.01.011.