OKÜLER İLAÇ TAŞIYICI SİSTEM OLARAK LİPİT BAZLI NANOPARTİKÜLLER

Year 2024, Volume: 48 Issue: 2, 751 - 765, 20.05.2024

Heybet Kerem Polat , Eren Aytekin , Nasıf Fatih Karakuyu , Nihat Kurt , Yonca Yazıksız

https://doi.org/10.33483/jfpau.1420064

Abstract

Amaç: Bu derleme kapsamında, oküler kullanımdaki katı lipit nanopartikül (KLN) ve nanoyapılı lipit taşıyıcı (NLT) sistemlerine, bu formülasyonların sterilizasyonuna ve tasarımla kalite (QbD) hakkında yapılan son araştırmaları tartışmak amaçlanmıştır.
Sonuç ve Tartışma: Göze ilaç taşınması son yıllardaki gelişmelere rağmen hala karmaşık bir sorun olarak devem etmekte ve etkili ilaç taşınabilmesi için yenilikçi yaklaşımlara ihtiyaç duyulan bir alandır. Bu derlemede, yenilikçi yaklaşımlardan olan KLN’ler ve NLT’lerin oftalmik ilaç uygulamalarında sağladıkları üstünlükler güncel literatür örnekleriyle tartışılmıştır. KLN’ler oda sıcaklığında katı halde bulunan lipitlerin genellikle eritilmesi ya da çeşitli solvanlarda çözündürülmesi ile hazırlanan lipit partiküllerdir. NLT’ler ise yapısında katı lipitlerle birlikte oda sıcaklığında sıvı halde bulunan lipitleri de içermektedir. Oküler ilaç uygulamalarında kritik aşamalardan biri de sterilizasyon basamağıdır. Uygun sterilizasyon işleminin seçiminde, kullanılan lipitlerin erime dereceleri, serbest radikal oluşturma eğilimleri ve partikül büyüklükleri göz önünde bulundurulmalıdır. Sonuç olarak, KLN ve NLT’ler hem biyouyumluluk hem de etkililik anlamında oküler tedaviler için umut vadeden ilaç taşıyıcı sistemlerdir. Derleme kapsamında incelenen literatür çalışmaları da bu çıkarımı desteklemektedir. Ancak saklama süresince karşılaşılabilen stabilite sorunları ve tekrarlanabilir büyük ölçekte üretim konusunda yaşanan sıkıntılar nedeniyle klinik tedavide yeterince kullanılamamaktadır. Bu sorunların çözümü aşamasında QbD’nin etkili olacağı düşünülmektedir.

Keywords

Göz, katı lipid nanopartiküller, nano yapılı lipit taşıyıcılar, QbD, sterilizasyon

LIPID-BASED NANOPARTICLES AS OCULAR DRUG DELIVERY SYSTEM

Abstract

Objective: Within the scope of this review, it aims to discuss the latest research on solid lipid nanoparticle (KLN) and nanostructured lipid carrier (NLT) systems for ocular use, sterilization of these formulations, and quality by design (QbD).
Result and Discussion: Despite the developments in recent years, drug delivery to the eye remains a complex problem and is an area where innovative approaches are needed for effective drug delivery. This review discusses the advantages of KLNs and NLTs, innovative approaches in ophthalmic drug applications, with examples from current literature. KLNs are lipid particles prepared by melting solid lipids at room temperature or dissolving them in various solvents. NLTs, on the other hand, contain solid lipids in their structure, as well as lipids that are liquid at room temperature. One of the critical stages in ocular drug applications is the sterilization step. In choosing the appropriate sterilization process, the melting degrees, free radical formation tendencies, and particle sizes of the lipids used should be considered. In conclusion, KLNs and NLTs are promising drug delivery systems for ocular treatments in terms of biocompatibility and efficacy. The studies examined within the scope of the review also support this inference. However, it cannot be used adequately in clinical treatment due to stability problems that may be encountered during storage and difficulties in reproducible large-scale production. It is thought that QbD will be effective in solving these problems.

Keywords

Eye, nanostructured lipid carriers, QbD, solid lipid nanoparticles, sterilization

References

• 1. Bourne, R., Steinmetz, J.D., Flaxman, S., Briant, P.S., Taylor, H.R., Resnikoff, S., Casson, R.J., Abdoli, A., Abu-Gharbieh, E., Afshin, A., Ahmadieh, H., Akalu, Y., Alamneh, A.A., Alemayehu, W., Alfaar, A.S., Alipour, V., Anbesu, E.W., Androudi, S., Arabloo, J., Arditi, A., Asaad, M., Bagli, E., Baig, A.A., Bärnighausen, T.W., Battaglia Parodi, M., Bhagavathula, A.S., Bhardwaj, N., Bhardwaj, P., Bhattacharyya, K., Bijani, A., Bikbov, M., Bottone, M., Braithwaite, T., Bron, A.M., Butt, Z.A., Cheng, C.Y., Chu, D.T., Cicinelli, M.V., Coelho, J.M., Dagnew, B., Dai, X., Dana, R., Dandona, L., Dandona, R., Del Monte, M.A., Deva, J.P., Diaz, D., Djalalinia, S., Dreer, L.E., Ehrlich, J.R., Ellwein, L.B., Emamian, M.H., Fernandes, A.G., Fischer, F., Friedman, D.S., Furtado, J.M., Gaidhane, A.M., Gaidhane, S., Gazzard, G., Gebremichael, B., George, R., Ghashghaee, A., Golechha, M., Hamidi, S., Hammond, B.R., Hartnett, M. E.R., Hartono, R.K., Hay, S.I., Heidari, G., Ho, H.C., Hoang, C.L., Househ, M., Ibitoye, S.E., Ilic, I.M., Ilic, M.D., Ingram, A.D., Irvani, S.S.N., Jha, R.P., Kahloun, R., Kandel, H., Kasa, A.S., Kempen, J.H., Keramati, M., Khairallah, M., Khan, E.A., Khanna, R.C., Khatib, M.N., Kim, J.E., Kim, Y.J., Kisa, S., Kisa, A., Koyanagi, A., Kurmi, O.P., Lansingh, V.C., Leasher, J.L., Leveziel, N., Limburg, H., Majdan, M., Manafi, N., Mansouri, K., McAlinden, C., Mohammadi, S.F., Mohammadian-Hafshejani, A., Mohammadpourhodki, R., Mokdad, A.H., Moosavi, D., Morse, A.R., Naderi, M., Naidoo, K.S., Nangia, V., Nguyen, C.T., Nguyen, H.L.T., Ogundimu, K., Olagunju, A.T., Ostroff, S.M., Panda-Jonas, S., Pesudovs, K., Peto, T., Quazi Syed, Z., Rahman, M.H.U., Ramulu, P.Y., Rawaf, S., Rawaf, D.L., Reinig, N., Robin, A.L., Rossetti, L., Safi, S., Sahebkar, A., Samy, A.M., Saxena, D., Serle, J.B., Shaikh, M.A., Shen, T.T., Shibuya, K., Shin, J. Il, Silva, J.C., Silvester, A., Singh, J.A., Singhal, D., Sitorus, R.S., Skiadaresi, E., Skirbekk, V., Soheili, A., Sousa, R.A.R.C., Spurlock, E.E., Stambolian, D., Taddele, B.W., Tadesse, E.G., Tahhan, N., Tareque, M.I., Topouzis, F., Tran, B.X., Travillian, R.S., Tsilimbaris, M.K., Varma, R., Virgili, G., Wang, Y.X., Wang, N., West, S.K., Wong, T.Y., Zaidi, Z., Zewdie, K.A., Jonas, J.B., Vos, T. (2021). Trends in prevalence of blindness and distance and near vision impairment over 30 years: An analysis for the global burden of disease study. The Lancet Global Health, 9(2), e130-e143. [CrossRef]
• 2. Polat, H.K., Kurt, N., Aytekin, E., Bozdağ Pehlivan, S., Çalış, S. (2022). Novel drug delivery systems to ımprove the treatment of keratitis. Journal of Ocular Pharmacology and Therapeutics, 38(6), 376-395. [CrossRef]
• 3. Taghe, S., Mirzaeei, S. (2019). Preparation and characterization of novel, mucoadhesive ofloxacin nanoparticles for ocular drug delivery. Brazilian Journal of Pharmaceutical Sciences, 55, e17105. [CrossRef]
• 4. Polat, H.K., Bozdağ Pehlivan, S., Özkul, C., Çalamak, S., Öztürk, N., Aytekin, E., Fırat, A., Ulubayram, K., Kocabeyoğlu, S., İrkeç, M., Çalış, S. (2020). Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation. International Journal of Pharmaceutics, 585, 119552. [CrossRef]
• 5. Weng, Y., Liu, J., Jin, S., Guo, W., Liang, X., Hu, Z. (2017). Nanotechnology-based strategies for treatment of ocular disease. Acta Pharmaceutica Sinica B, 7(3), 281-291. [CrossRef]
• 6. Bachu, R., Chowdhury, P., Al-Saedi, Z., Karla, P., Boddu, S. (2018). Ocular drug delivery barriers-role of nanocarriers in the treatment of anterior segment ocular diseases. Pharmaceutics, 10(1), 28. [CrossRef]
• 7. Yu, L.X., Amidon, G., Khan, M.A., Hoag, S.W., Polli, J., Raju, G.K., Woodcock, J. (2014). Understanding pharmaceutical quality by design. The AAPS Journal, 16(4), 771-783. [CrossRef]
• 8. Politis, N., Colombo, S., Colombo, P.G.M., Rekkas, D. (2017). Design of experiments (DoE) in pharmaceutical development. Drug Development and Industrial Pharmacy, 43(6), 889-901. [CrossRef]
• 9. Järvinen, K., Järvinen, T., Urtti, A. (1995). Ocular absorption following topical delivery. Advanced Drug Delivery Reviews, 16(1), 3-19. [CrossRef]
• 10. Schoenwald, R.D., Deshpande, G.S., Rethwisch, D.G., Barfknecht, C.F. (1997). Penetration into the anterior chamber via the conjunctival/scleral pathway. Journal of Ocular Pharmacology and Therapeutics, 13(1), 41–59. [CrossRef]
• 11. Bhatt, P., Kelly, S., Sutariya, V. (2019). Nanoscale delivery systems in treatment of posterior ocular neovascularization: Strategies and potential applications. Therapeutic Delivery, 10(11), 737-747. [CrossRef]
• 12. Özkiriş, A., Erkiliç, K. (2005). Complications of intravitreal injection of triamcinolone acetonide. Canadian Journal of Ophthalmology, 40(1), 63-68. [CrossRef]
• 13. Peng, C., Kuang, L., Zhao, J., Ross, A.E., Wang, Z., Ciolino, J.B. (2022). Bibliometric and visualized analysis of ocular drug delivery from 2001 to 2020. Journal of Controlled Release, 345, 625-645. [CrossRef]
• 14. Gugleva, V., Andonova, V. (2023). Recent progress of solid lipid nanoparticles and nanostructured lipid carriers as ocular drug delivery platforms. Pharmaceuticals, 16(3), 474. [CrossRef]
• 15. Youssef, A.A.A., Dudhipala, N., Majumdar, S. (2022). Dual drug loaded lipid nanocarrier formulations for topical ocular applications. International Journal of Nanomedicine, 17, 2283-2299. [CrossRef]
• 16. Mun, E.A., Morrison, P.W., Williams, A.C., Khutoryanskiy, V.V. (2014). On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein. Molecular Pharmaceutics, 11(10), 3556–3564. [CrossRef]
• 17. Honary, S., Zahir, F. (2013). Effect of zeta potential on the properties of nano-drug delivery systems-a review (Part 2). Tropical Journal of Pharmaceutical Research, 12, 265-273. [CrossRef]
• 18. Hanaor, D., Michelazzi, M., Leonelli, C., Sorrell, C.C. (2012). The effects of carboxylic acids on the aqueous dispersion and electrophoretic deposition of ZrO2. Journal of the European Ceramic Society, 32, 235-244. [CrossRef]
• 19. González-Fernández, F.M., Bianchera, A., Gasco, P., Nicoli, S., Pescina, S. (2021). Lipid-based nanocarriers for ophthalmic administration: Towards experimental design ımplementation. Pharmaceutics, 13(4), 447. [CrossRef]
• 20. Aytekin, E., Öztürk, N., Vural, İ., Polat, H.K., Çakmak, H.B., Çalış, S., Pehlivan, S.B. (2020). Design of ocular drug delivery platforms and in vitro-in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment. Journal of Controlled Release, 324, 238-249. [CrossRef]
• 21. Mukherjee, S., Ray, S., Thakur, R.S. (2009). Solid lipid nanoparticles: A modern formulation approach in drug delivery system. Indian Journal of Pharmaceutical Sciences, 71(4), 349-358. [CrossRef]
• 22. Gomaa, E., Fathi, H.A., Eissa, N.G., Elsabahy, M. (2022). Methods for preparation of nanostructured lipid carriers. Methods, 199, 3-8. [CrossRef]
• 23. Gordillo-Galeano, A., Mora-Huertas, C.E. (2018). Solid lipid nanoparticles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. European Journal of Pharmaceutics and Biopharmaceutics, 133, 285-308. [CrossRef]
• 24. Balamurugan K., Chintamani P. (2018). Lipid nano particulate drug delivery: An overview of the emerging trend. The Pharma Innovation Journal, 7(7), 779-789.
• 25. Sumera, Anwar, A., Ovais, M., Khan, A., Raza, A. (2017). Docetaxel‐loaded solid lipid nanoparticles: A novel drug delivery system. IET Nanobiotechnology, 11(6), 621-629. [CrossRef]
• 26. Silva, A., Martins-Gomes, C., Coutinho, T., Fangueiro, J., Sanchez-Lopez, E., Pashirova, T., Andreani, T., Souto, E. (2019). Soft cationic nanoparticles for drug delivery: Production and cytotoxicity of solid lipid nanoparticles (SLNs). Applied Sciences, 9(20), 4438. [CrossRef]
• 27. Liang, Z., Zhang, Z., Yang, J., Lu, P., Zhou, T., Li, J., Zhang, J. (2021). Assessment to the antifungal effects in vitro and the ocular pharmacokinetics of solid-lipid nanoparticle in rabbits. International Journal of Nanomedicine, 16, 7847-7857. [CrossRef]
• 28. Nair, A., Shah, J., Al-Dhubiab, B., Jacob, S., Patel, S., Venugopala, K., Morsy, M., Gupta, S., Attimarad, M., Sreeharsha, N., Shinu, P. (2021). Clarithromycin solid lipid nanoparticles for topical ocular therapy: Optimization, evaluation and in vivo studies. Pharmaceutics, 13(4), 523. [CrossRef]
• 29. Bonaccorso, A., Pepe, V., Zappulla, C., Cimino, C., Pricoco, A., Puglisi, G., Giuliano, F., Pignatello, R., Carbone, C. (2021). Sorafenib repurposing for ophthalmic delivery by lipid nanoparticles: A preliminary study. Pharmaceutics, 13(11), 1956. [CrossRef]
• 30. Eid, H.M., Elkomy, M.H., El Menshawe, S.F., Salem, H.F. (2019). Development, optimization, and ın vitro/ın vivo characterization of enhanced lipid nanoparticles for ocular delivery of ofloxacin: The ınfluence of pegylation and chitosan coating. AAPS PharmSciTech, 20(5), 183. [CrossRef]
• 31. Dang, H., Dong, C., Zhang, L. (2022). Sustained latanoprost release from PEGylated solid lipid nanoparticle-laden soft contact lens to treat glaucoma. Pharmaceutical Development and Technology, 27(2), 127-133. [CrossRef]
• 32. Fengzhen, W., Mingwan, Z., Dongsheng, Z., Yuan, H., Li, C., Sunmin, J., Kun, S., Rui, L. (2018). Preparation, optimization, and characterization of chitosancoated solid lipid nanoparticles for ocular drug delivery. The Journal of Biomedical Research, 32(6), 411. [CrossRef]
• 33. Sun, K., Hu, K. (2021). Preparation and characterization of tacrolimus-loaded slns in situ gel for ocular drug delivery for the treatment of ımmune conjunctivitis. Drug Design, Development and Therapy, Volume 15, 141-150. [CrossRef]
• 34. El-Emam, G.A., Girgis, G.N., Hamed, M.F., El-Azeem Soliman, O.A., Abd El Gawad, A.E.G.H. (2021). Formulation and pathohistological study of mizolastine-solid lipid nanoparticles-loaded ocular hydrogels. International Journal of Nanomedicine, Volume 16, 7775-7799. [CrossRef]
• 35. Kiss, E.L., Berkó, S., Gácsi, A., Kovács, A., Katona, G., Soós, J., Csányi, E., Gróf, I., Harazin, A., Deli, M.A., Budai-Szűcs, M. (2019). Design and optimization of nanostructured lipid carrier containing dexamethasone for ophthalmic use. Pharmaceutics, 11(12), 679. [CrossRef]
• 36. Apostolou, M., Assi, S., Fatokun, A.A., Khan, I. (2021). The effects of solid and liquid lipids on the physicochemical properties of nanostructured lipid carriers. Journal of Pharmaceutical Sciences, 110(8), 2859-2872. [CrossRef]
• 37. Bang, K.H., Na, Y.G., Huh, H.W., Hwang, S.J., Kim, M.S., Kim, M., Lee, H.K., Cho, C.W. (2019). The delivery strategy of paclitaxel nanostructured lipid carrier coated with platelet membrane. Cancers, 11(6), 807. [CrossRef]
• 38. Haider, M., Abdin, S.M., Kamal, L., Orive, G. (2020). Nanostructured lipid carriers for delivery of chemotherapeutics: a review. Pharmaceutics, 12(3), 288. [CrossRef]
• 39. Khosa, A., Reddi, S., Saha, R.N. (2018). Nanostructured lipid carriers for site-specific drug delivery. Biomedicine & Pharmacotherapy, 103, 598-613. [CrossRef]
• 40. Varela-Fernández, R., García-Otero, X., Díaz-Tomé, V., Regueiro, U., López-López, M., González-Barcia, M., Isabel Lema, M., Javier Otero-Espinar, F. (2022). Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 172, 144-156. [CrossRef]
• 41. Kumari, S., Dandamudi, M., Rani, S., Behaeghel, E., Behl, G., Kent, D., O’Reilly, N.J., O’Donovan, O., McLoughlin, P., Fitzhenry, L. (2021). Dexamethasone-loaded nanostructured lipid carriers for the treatment of dry eye disease. Pharmaceutics, 13(6), 905. [CrossRef]
• 42. Uner, B., Ozdemir, S., Tas, C., Uner, M., Ozsoy, Y. (2023). Loteprednol-loaded nanoformulations for corneal delivery by quality-by-design concepts: optimization, characterization, and anti-inflammatory Activity. AAPS PharmSciTech, 24(4), 92. [CrossRef]
• 43. Nirbhavane, P., Sharma, G., Singh, B., Begum, G., Jones, M.C., Rauz, S., Vincent, R., Denniston, A.K., Hill, L.J., Katare, O.P. (2020). Triamcinolone acetonide loaded-cationic nano-lipoidal formulation for uveitis: Evidences of improved biopharmaceutical performance and anti-inflammatory activity. Colloids and Surfaces B: Biointerfaces, 190, 110902. [CrossRef]
• 44. Chen, L., Wu, R. (2022). Brinzolamide- and latanoprost-loaded nano lipid carrier prevents synergistic retinal damage in glaucoma. Acta Biochimica Polonica, 69(2), 423-428. [CrossRef]
• 45. Li, Q., Yang, X., Zhang, P., Mo, F., Si, P., Kang, X., Wang, M., Zhang, J. (2021). Dasatinib loaded nanostructured lipid carriers for effective treatment of corneal neovascularization. Biomaterials Science, 9(7), 2571-2583. [CrossRef]
• 46. Pai, R.V., Vavia, P.R. (2020). Chitosan oligosaccharide enhances binding of nanostructured lipid carriers to ocular mucins: Effect on ocular disposition. International Journal of Pharmaceutics, 577, 119095. [CrossRef]
• 47. Tan, G., Li, J., Song, Y., Yu, Y., Liu, D., Pan, W. (2019). Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome. Acta Biomaterialia, 99, 350-362. [CrossRef]
• 48. Abdelhakeem, E., El-nabarawi, M., Shamma, R. (2021). Effective ocular delivery of eplerenone using nanoengineered lipid carriers in rabbit model. International Journal of Nanomedicine, 16, 4985–5002. [CrossRef]
• 49. Abdelmonem, R., Al-Samadi, I.E.I., El Nashar, R.M., Jasti, B.R., El-Nabarawi, M.A. (2022). Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization, in-vitro , ex-vivo , and in-vivo studies evaluation. Drug Delivery, 29(1), 2868-2882. [CrossRef]
• 50. Yu, Y., Xu, S., Yu, S., Li, J., Tan, G., Li, S., Pan, W. (2020). A hybrid genipin-cross-linked hydrogel/nanostructured lipid carrier for ocular drug delivery: Cellular, ex vivo, and in vivo evaluation. ACS Biomaterials Science & Engineering, 6(3), 1543-1552. [CrossRef]
• 51. Gokce, E.H., Sandri, G., Bonferoni, M.C., Rossi, S., Ferrari, F., Güneri, T., Caramella, C. (2008). Cyclosporine A loaded SLNs: Evaluation of cellular uptake and corneal cytotoxicity. International Journal of Pharmaceutics, 364(1), 76-86. [CrossRef]
• 52. Youshia, J., Kamel, A.O., El Shamy, A., Mansour, S. (2021). Gamma sterilization and in vivo evaluation of cationic nanostructured lipid carriers as potential ocular delivery systems for antiglaucoma drugs. European Journal of Pharmaceutical Sciences, 163, 105887. [CrossRef]
• 53. Pepic, I., Hafner, A., Lovric, J., Perina Lakos, G. (2014). Nanotherapeutics in the EU: An overview on current state and future directions. International Journal of Nanomedicine, 9(1), 1005. [CrossRef]
• 54. Zhang, L., Mao, S. (2017). Application of quality by design in the current drug development. Asian Journal of Pharmaceutical Sciences, 12(1), 1-8. [CrossRef]
• 55. Cunha, S., Costa, C.P., Moreira, J.N., Sousa Lobo, J.M., Silva, A.C. (2020). Using the quality by design (QbD) approach to optimize formulations of lipid nanoparticles and nanoemulsions: A review. Nanomedicine: Nanotechnology, Biology and Medicine, 28, 102206. [CrossRef]
• 56. Rathod, V.R., Shah, D.A., Dave, R.H. (2020). Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: Reformulation screening studies and statistical hybrid-design for optimization of variables. Drug development and industrial pharmacy, 46(3), 443-455. [CrossRef]
• 57. Gonzalez-Mira, E., Egea, M.A., Souto, E.B., Calpena, A.C., García, M.L. (2011). Optimizing flurbiprofen-loaded NLC by central composite factorial design for ocular delivery. Nanotechnology, 22(4), 045101. [CrossRef]
• 58. Kiss, E.L., Berkó, S., Gácsi, A., Kovács, A., Katona, G., Soós, J., Csányi, E., Gróf, I., Harazin, A., Deli, M.A., Balogh, G.T., Budai-Szűcs, M. (2020). Development and characterization of potential ocular mucoadhesive nano lipid carriers using full factorial design. Pharmaceutics, 12(7), 682. [CrossRef]