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Chitosan and its Derivatives for Ocular Delivery Formulations: Recent Advances and Developments

Alexandra Zamboulis, Stavroula Nanaki, Georgia Michailidou and 5 more

Polymers · 2020 · Review · CC BY

doi:10.3390/polym12071519

Abstract

Chitosan (CS) is a hemi-synthetic cationic linear polysaccharide produced by the deacetylation of chitin. CS is non-toxic, highly biocompatible, and biodegradable, and it has a low immunogenicity. Additionally, CS has inherent antibacterial properties and a mucoadhesive character and can disrupt epithelial tight junctions, thus acting as a permeability enhancer. As such, CS and its derivatives are well-suited for the challenging field of ocular drug delivery. In the present review article, we will discuss the properties of CS that contribute to its successful application in ocular delivery before reviewing the latest advances in the use of CS for the development of novel ophthalmic delivery systems. Colloidal nanocarriers (nanoparticles, micelles, liposomes) will be presented, followed by CS gels and lenses and ocular inserts. Finally, instances of CS coatings, aiming at conferring mucoadhesiveness to other matrixes, will be presented.

References 320

  1. 1.

    Sánchez-López E., Espina M., Doktorovova S., Souto E.B., García M.L. Lipid nanoparticles (SLN, NLC): Overcoming the anatomical and physiological barriers of the eye—Part I—Barriers and determining factors in ocular delivery. Eur. J. Pharm. Biopharm. 2017;110:70-75.

    Not in our library10.1016/j.ejpb.2016.10.009

  2. 2.

    Jumelle C., Gholizadeh S., Annabi N., Dana R. Advances and limitations of drug delivery systems formulated as eye drops. J. Control. Release. 2020;321:1-22.

    Not in our library10.1016/j.jconrel.2020.01.057

  3. 3.

    Souto E.B., Dias-Ferreira J., López-Machado A., Ettcheto M., Cano A., Espuny A.C., Espina M., Garcia M.L., Sánchez-López E. Advanced formulation approaches for ocular drug delivery: State-of-the-art and recent patents. Pharmaceutics. 2019;11:460.

    Not in our library10.3390/pharmaceutics11090460

  4. 4.

    Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv. Drug Deliv. Rev. 2006;58:1131-1135.

    Not in our library10.1016/j.addr.2006.07.027

  5. 5.

    Gaudana R., Ananthula H.K., Parenky A., Mitra A.K. Ocular drug delivery. AAPS J. 2010;12:348-360.

    Not in our library10.1208/s12248-010-9183-3

  6. 6.

    Alvarez-Lorenzo C., Yañez F., Concheiro A. Ocular drug delivery from molecularly-imprinted contact lenses. J. Drug Deliv. Sci. Technol. 2010;20:237-248.

    Not in our library10.1016/s1773-2247(10)50041-8

  7. 7.

    Patel A., Cholkar K., Agrahari V., Mitra A.K. Ocular drug delivery systems: An overview. World J. Pharmacol. 2013;2:47-64.

    Not in our library10.5497/wjp.v2.i2.47

  8. 8.
  9. 9.

    Gaudana R., Jwala J., Boddu S.H.S., Mitra A.K. Recent perspectives in ocular drug delivery. Pharm. Res. 2009;26:1197-1216.

    Not in our library10.1007/s11095-008-9694-0

  10. 10.

    Achouri D., Alhanout K., Piccerelle P., Andrieu V. Recent advances in ocular drug delivery. Drug Dev. Ind. Pharm. 2013;39:1599-1617.

    Not in our library10.3109/03639045.2012.736515

  11. 11.

    Duxfield L., Sultana R., Wang R., Englebretsen V., Deo S., Rupenthal I.D., Al-Kassas R. Ocular delivery systems for topical application of anti-infective agents. Drug Dev. Ind. Pharm. 2016;42:1-11.

    Not in our library10.3109/03639045.2015.1070171

  12. 12.

    Khare A., Grover K., Pawar P., Singh I. Mucoadhesive polymers for enhancing retention in ocular drug delivery: A critical review. Rev. Adhes. Adhes. 2014;2:467-502.

    Not in our library10.7569/raa.2014.097310

  13. 13.

    White C.J., Tieppo A., Byrne M.E. Controlled drug release from contact lenses: A comprehensive review from 1965-present. J. Drug Deliv. Sci. Technol. 2011;21:369-384.

    Not in our library10.1016/s1773-2247(11)50062-0

  14. 14.

    Fulgêncio G., De O., Viana F.A.B., Ribeiro R.R., Yoshida M.I., Faraco A.G., Da Silva Cunha-Júnior A. New mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate: In vivo evaluation. J. Ocul. Pharmacol. Ther. 2012;28:350-358.

    Not in our library10.1089/jop.2011.0174

  15. 15.
  16. 16.

    Huang D., Chen Y.S., Rupenthal I.D. Overcoming ocular drug delivery barriers through the use of physical forces. Adv. Drug Deliv. Rev. 2018;126:96-112.

    Not in our library10.1016/j.addr.2017.09.008

  17. 17.

    Gote V., Sikder S., Sicotte J., Pal D. Ocular drug delivery: Present innovations and future challenges. J. Pharmacol. Exp. Ther. 2019;370:602-624.

    Not in our library10.1124/jpet.119.256933

  18. 18.

    Cao Y., Samy K.E., Bernards D.A., Desai T.A. Recent advances in intraocular sustained—Release drug delivery devices. Drug Discov. Today. 2019;24:1694-1700.

    Not in our library10.1016/j.drudis.2019.05.031

  19. 19.

    Agban Y., Thakur S.S., Mugisho O.O., Rupenthal I.D. Depot formulations to sustain periocular drug delivery to the posterior eye segment. Drug Discov. Today. 2019;24:1458-1469.

    Not in our library10.1016/j.drudis.2019.03.023

  20. 20.

    Maharjan P., Cho K.H., Maharjan A., Shin M.C., Moon C., Min K.A. Pharmaceutical challenges and perspectives in developing ophthalmic drug formulations. J. Pharm. Investig. 2019;49:215-228.

    Not in our library10.1007/s40005-018-0404-6

  21. 21.

    Bhattacharjee A., Das P.J., Adhikari P., Marbaniang D., Pal P., Ray S., Mazumder B. Novel drug delivery systems for ocular therapy: With special reference to liposomal ocular delivery. Eur. J. Ophthalmol. 2019;29:113-126.

    Not in our library10.1177/1120672118769776

  22. 22.

    Suri R., Beg S., Kohli K. Target strategies for drug delivery bypassing ocular barriers. J. Drug Deliv. Sci. Technol. 2020;55:101389.

    Not in our library10.1016/j.jddst.2019.101389

  23. 23.

    Ntohogian S., Gavriliadou V., Christodoulou E., Nanaki S., Lykidou S., Naidis P., Mischopoulou L., Barmpalexis P., Nikolaidis N., Bikiaris D.N. Chitosan nanoparticles with encapsulated natural and Uf-purified annatto and saffron for the preparation of UV protective cosmetic emulsions. Molecules. 2018;23:2107.

    Not in our library10.3390/molecules23092107

  24. 24.

    Tashakori-Sabzevar F., Mohajeri S.A. Development of ocular drug delivery systems using molecularly imprinted soft contact lenses. Drug Dev. Ind. Pharm. 2015;41:703-713.

    Not in our library10.3109/03639045.2014.948451

  25. 25.

    Kumar A., Vimal A., Kumar A. Why chitosan? From properties to perspective of mucosal drug delivery. Int. J. Biol. Macromol. 2016;91:615-622.

    Not in our library10.1016/j.ijbiomac.2016.05.054

  26. 26.
  27. 27.
  28. 28.

    Green S., Roldo M., Douroumis D., Bouropoulos N., Lamprou D., Fatouros D.G. Chitosan derivatives alter release profiles of model compounds from calcium phosphate implants. Carbohydr. Res. 2009;344:901-907.

    Not in our library10.1016/j.carres.2009.02.022

  29. 29.

    Kean T., Thanou M. Biodegradation, biodistribution and toxicity of chitosan. Adv. Drug Deliv. Rev. 2010;62:3-11.

    Not in our library10.1016/j.addr.2009.09.004

  30. 30.

    Mendes A.C., Moreno J.S., Hanif M., Douglas T.E.L., Chen M., Chronakis I.S. Morphological, mechanical and mucoadhesive properties of electrospun chitosan/phospholipid hybrid nanofibers. Int. J. Mol. Sci. 2018;19:2266.

    Not in our library10.3390/ijms19082266

  31. 31.

    Hafezi F., Scoutaris N., Douroumis D., Boateng J. 3D printed chitosan dressing crosslinked with genipin for potential healing of chronic wounds. Int. J. Pharm. 2019;560:406-415.

    Not in our library10.1016/j.ijpharm.2019.02.020

  32. 32.

    Michailidou G., Ainali N.M., Xanthopoulou E., Nanaki S., Kostoglou M., Koukaras E.N., Bikiaris D.N. Effect of poly(vinyl alcohol) on nanoencapsulation of budesonide in chitosan nanoparticles via ionic gelation and its improved bioavailability. Polymers. 2020;12:1101.

    Not in our library10.3390/polym12051101

  33. 33.

    Roy S., Pal K., Anis A., Pramanik K., Prabhakar B. Polymers in mucoadhesive drug-delivery systems: A brief note. Des. Monomers Polym. 2009;12:483-495.

    Not in our library10.1163/138577209x12478283327236

  34. 34.
  35. 35.

    Ensign L.M., Cone R., Hanes J. Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Adv. Drug Deliv. Rev. 2012;64:557-570.

    Not in our library10.1016/j.addr.2011.12.009

  36. 36.

    Boegh M., Nielsen H.M. Mucus as a barrier to drug delivery—Understanding and mimicking the barrier properties. Basic Clin. Pharmacol. Toxicol. 2015;116:179-186.

    Not in our library10.1111/bcpt.12342

  37. 37.

    Peppas N.A., Buri P.A. Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. J. Control. Release. 1985;2:257-275.

    Not in our library10.1016/0168-3659(85)90050-1

  38. 38.

    Mikos A.G., Peppas N.A., Lenaerts V.M., Gurny R. Scaling concepts and molecular theories of adhesion of synthetic polymers to glycoproteinic networks. Bioadhesive Drug Delivery Systems. 1990;25-42.

    Not in our library

  39. 39.

    Khutoryanskiy V.V. Advances in mucoadhesion and mucoadhesive polymers. Macromol. Biosci. 2011;11:748-764.

    Not in our library10.1002/mabi.201000388

  40. 40.

    Bassi Da Silva J., Ferreira S.B. de S.; de Freitas, O.; Bruschi, M.L. A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems. Drug Dev. Ind. Pharm. 2017;43:1053-1070.

    Not in our library10.1080/03639045.2017.1294600

All 320 references

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