Lutein-Loaded Solid Lipid Nanoparticles for Ocular Delivery: Statistical Optimization and Ex Vivo Evaluation

Journal of Pharmaceutical Innovation (2021)Cite this article

Abstract

Purpose

This study aimed to develop and optimize lutein-loaded solid lipid nanoparticles (Lu-SLN) for ocular delivery. The objective was to achieve the mean particle size of Lu-SLN less than 100 nm, sustain the drug release up to 8 h, and evaluate the corneal permeation parameters of the optimized batch.

Methods

Lu-SLN were prepared by hot homogenization and cold dilution method. The Plackett-Burman screening design and 32 full factorial design were adopted sequentially to study the effect of various formulation and process variables, and further optimized with the help of desirability function.

Results

The statistical designs revealed that the amount of Gelucire® 44/14 and homogenization speed had a significant effect (P < 0.05) on the mean particle size and % drug release of Lu-SLN. The optimized formulation prepared with the help of the desirability function showed a mean particle size of 79.70 nm and sustained the drug release up to 8 h in simulated tear fluid. The apparent permeability coefficient and steady-state flux of the optimized batch were found to be \(1.09 \times {10}^{-4}\frac{\mathrm{cm}}{\mathrm{h}}\) and \(7.33 \times {10}^{-2}\frac{{\mu \mathrm{g}}}{{\mathrm{cm}}^{2}}/\mathrm{h}\), respectively, and the corneal hydration was found to be 78.35%.

Conclusions

Lu-SLN with chosen objectives can be successfully prepared by hot homogenization technique and ex vivo evaluation revealed that optimized formulation avoided any damage to the cornea.

Graphical abstract

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

References

  1. 1.

    World Health Organization. Report on Blindness and vision impairment prevention. 2020. https://www.who.int/blindness/causes/priority/en/index7.html. Last accessed on 4 May 2020.

  2. 2.

    Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet. 2018;392(10153):1147–59. https://doi.org/10.1016/s0140-6736(18)31550-2.

    Article  PubMed  Google Scholar 

  3. 3.

    Xu Q, Cao S, Rajapakse S, Matsubara JA. Understanding AMD by analogy: systematic review of lipid-related common pathogenic mechanisms in AMD, AD, AS and GN. Lipids Health Dis. 2018;17(1):3. https://doi.org/10.1186/s12944-017-0647-7.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Muñoz-Ramón PV, Hernández Martínez P, Muñoz-Negrete FJ. New therapeutic targets in the treatment of age-related macular degeneration. Arch Soc Esp Oftalmol (English Edition). 2020;95(2):75–83. https://doi.org/10.1016/j.oftale.2019.09.013.

    Article  Google Scholar 

  5. 5.

    Wong CW, Wong TT. Posterior segment drug delivery for the treatment of exudative age-related macular degeneration and diabetic macular oedema. Br J Ophthalmol. 2019;103(10):1356–60. https://doi.org/10.1136/bjophthalmol-2018-313462.

    Article  PubMed  Google Scholar 

  6. 6.

    Jiang S, Franco YL, Zhou Y, Chen J. Nanotechnology in retinal drug delivery. Int J Ophthalmol. 2018;11(6):1038–44. https://doi.org/10.18240/ijo.2018.06.23.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Wang D, Jiang Y, He M, Scheetz J, Wang W. Disparities in the global burden of age-related macular degeneration: an analysis of trends from 1990 to 2015. Curr Eye Res. 2019;44(6):657–63. https://doi.org/10.1080/02713683.2019.1576907.

    Article  PubMed  Google Scholar 

  8. 8.

    More P, Almuhtaseb H, Smith D, Fraser S, Lotery AJ. Socio-economic status and outcomes for patients with age-related macular degeneration. Eye (London, England). 2019;33(8):1224–31. https://doi.org/10.1038/s41433-019-0393-3.

    Article  Google Scholar 

  9. 9.

    Agrahari V, Mandal A, Agrahari V, Trinh HM, Joseph M, Ray A, et al. A comprehensive insight on ocular pharmacokinetics. Drug Deliv Transl Res. 2016;6(6):735–54. https://doi.org/10.1007/s13346-016-0339-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Al-Zamil WM, Yassin SA. Recent developments in age-related macular degeneration: a review. Clin Interv Aging. 2017;12:1313–30. https://doi.org/10.2147/cia.s143508.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Kumar-Singh R. The role of complement membrane attack complex in dry and wet AMD - from hypothesis to clinical trials. Exp Eye Res. 2019;184:266–77. https://doi.org/10.1016/j.exer.2019.05.006.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Sachdeva MM, Moshiri A, Leder HA, Scott AW. Endophthalmitis following intravitreal injection of anti-VEGF agents: long-term outcomes and the identification of unusual micro-organisms. J Ophthalmic Inflamm Infect. 2016;6(1):2. https://doi.org/10.1186/s12348-015-0069-5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Klein R, Lee KE, Tsai MY, Cruickshanks KJ, Gangnon RE, Klein BEK. Oxidized low-density lipoprotein and the incidence of age-related macular degeneration. Ophthalmology. 2019;126(5):752–8. https://doi.org/10.1016/j.ophtha.2018.12.026.

    Article  PubMed  Google Scholar 

  14. 14.

    Martin L. Targeting modifiable risk factors in age-related macular degeneration in optometric practice in Sweden. Clin Optom. 2017;9:77–83. https://doi.org/10.2147/opto.s129942.

    Article  Google Scholar 

  15. 15.

    Leung TW, Li RWH, Kee CS. Blue-light filtering spectacle lenses: optical and clinical performances. PLoS One. 2017;12(1):e0169114-e. https://doi.org/10.1371/journal.pone.0169114.

    CAS  Article  Google Scholar 

  16. 16.

    Roberts JE, Dennison J. The photobiology of lutein and zeaxanthin in the eye. J Ophthalmol. 2015;2015:687173. https://doi.org/10.1155/2015/687173.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Feng L, Nie K, Jiang H, Fan W. Effects of lutein supplementation in age-related macular degeneration. PLoS One. 2019;14(12):e0227048-e. https://doi.org/10.1371/journal.pone.0227048.

    CAS  Article  Google Scholar 

  18. 18.

    Yanai R, Chen S, Uchi SH, Nanri T, Connor KM, Kimura K. Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice. PLoS One. 2018;13(4):e0196037-e. https://doi.org/10.1371/journal.pone.0196037.

    CAS  Article  Google Scholar 

  19. 19.

    Bernstein PS, Li B, Vachali PP, Gorusupudi A, Shyam R, Henriksen BS, et al. Lutein, zeaxanthin, and meso-zeaxanthin: the basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease. Prog Retin Eye Res. 2016;50:34–66. https://doi.org/10.1016/j.preteyeres.2015.10.003.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Liu C, Chang D, Zhang X, Sui H, Kong Y, Zhu R, et al. Oral fast-dissolving films containing lutein nanocrystals for improved bioavailability: formulation development, in vitro and in vivo evaluation. AAPS PharmSciTech. 2017;18(8):2957–64. https://doi.org/10.1208/s12249-017-0777-2.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Buscemi S, Corleo D, Di Pace F, Petroni ML, Satriano A, Marchesini G. The effect of lutein on eye and extra-eye health. Nutrients. 2018;10(9):1321. https://doi.org/10.3390/nu10091321.

    CAS  Article  PubMed Central  Google Scholar 

  22. 22.

    Ranard KM, Jeon S, Mohn ES, Griffiths JC, Johnson EJ, Erdman JW Jr. Dietary guidance for lutein: consideration for intake recommendations is scientifically supported. Eur J Nutr. 2017;56(Suppl 3):37–42. https://doi.org/10.1007/s00394-017-1580-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Ochoa Becerra M, Mojica Contreras L, Hsieh Lo M, Mateos Díaz J, Castillo HG. Lutein as a functional food ingredient: stability and bioavailability. J Funct Foods. 2020;66:103771. https://doi.org/10.1016/j.jff.2019.103771.

    CAS  Article  Google Scholar 

  24. 24.

    Musch DC. Evidence for including lutein and zeaxanthin in oral supplements for age-related macular degeneration. JAMA Ophthalmology. 2014;132(2):139. https://doi.org/10.1001/jamaophthalmol.2013.7443.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Lombardo M, Villari V, Micali N, Roy P, Sousa SH, Lombardo G. Assessment of trans-scleral iontophoresis delivery of lutein to the human retina. J Biophotonics. 2017;11(3):e201700095. https://doi.org/10.1002/jbio.201700095.

    CAS  Article  Google Scholar 

  26. 26.

    Joachim N, Mitchell P, Burlutsky G, Kifley A, Wang JJ. The incidence and progression of age-related macular degeneration over 15 years. Ophthalmology. 2015;122(12):2482–9. https://doi.org/10.1016/j.ophtha.2015.08.002.

    Article  PubMed  Google Scholar 

  27. 27.

    Chittasupho C, Posritong P, Ariyawong P. Stability, cytotoxicity, and retinal pigment epithelial cell binding of hyaluronic acid-coated PLGA nanoparticles encapsulating lutein. AAPS PharmSciTech. 2018;20(1):1–13. https://doi.org/10.1208/s12249-018-1256-0.

    CAS  Article  Google Scholar 

  28. 28.

    Rodrigues GA, Lutz D, Shen J, Yuan X, Shen H, Cunningham J, et al. Topical drug delivery to the posterior segment of the eye: addressing the challenge of preclinical to clinical translation. Pharm Res. 2018;35(12):245. https://doi.org/10.1007/s11095-018-2519-x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Dubald M, Bourgeois S, Andrieu V, Fessi H. Ophthalmic drug delivery systems for antibiotherapy-a review. Pharmaceutics. 2018;10(1):10. https://doi.org/10.3390/pharmaceutics10010010.

    CAS  Article  PubMed Central  Google Scholar 

  30. 30.

    Awwad S, Mohamed Ahmed AHA, Sharma G, Heng JS, Khaw PT, Brocchini S, et al. Principles of pharmacology in the eye. Br J Pharmacol. 2017;174(23):4205–23. https://doi.org/10.1111/bph.14024.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Gote V, Sikder S, Sicotte J, Pal D. Ocular drug delivery: present innovations and future challenges. J Pharmacol Exp Ther. 2019;370(3):602–24. https://doi.org/10.1124/jpet.119.256933.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Souto EB, Dias-Ferreira J, López-Machado A, Ettcheto M, Cano A, Camins Espuny A, et al. Advanced formulation approaches for ocular drug delivery: state-of-the-art and recent patents. Pharmaceutics. 2019;11(9):460. https://doi.org/10.3390/pharmaceutics11090460.

    CAS  Article  PubMed Central  Google Scholar 

  33. 33.

    Meng T, Kulkarni V, Simmers R, Brar V, Xu Q. Therapeutic implications of nanomedicine for ocular drug delivery. Drug Discov Today. 2019;24(8):1524–38. https://doi.org/10.1016/j.drudis.2019.05.006.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Bachu RD, Chowdhury P, Al-Saedi ZHF, Karla PK, Boddu SHS. Ocular drug delivery barriers-role of nanocarriers in the treatment of anterior segment ocular diseases. Pharmaceutics. 2018;10(1):28. https://doi.org/10.3390/pharmaceutics10010028.

    CAS  Article  PubMed Central  Google Scholar 

  35. 35.

    Lynch C, Kondiah PPD, Choonara YE, du Toit LC, Ally N, Pillay V. Advances in biodegradable nano-sized polymer-based ocular drug delivery. Polymers. 2019;11(8):1371. https://doi.org/10.3390/polym11081371.

    CAS  Article  PubMed Central  Google Scholar 

  36. 36.

    Battaglia L, Serpe L, Foglietta F, Muntoni E, Gallarate M, Del Pozo RA, et al. Application of lipid nanoparticles to ocular drug delivery. Expert Opin Drug Deliv. 2016;13(12):1743–57. https://doi.org/10.1080/17425247.2016.1201059.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Puglia C, Offerta A, Carbone C, Bonina F, Pignatello R, Puglisi G. Lipid nanocarriers (LNC) and their applications in ocular drug delivery. Curr Med Chem. 2015;22(13):1589–602. https://doi.org/10.2174/0929867322666150209152259.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Wu M, Feng Z, Deng Y, Zhong C, Liu Y, Liu J, et al. Liquid antisolvent precipitation: an effective method for ocular targeting of lutein esters. Int J Nanomed. 2019;14:2667–81. https://doi.org/10.2147/ijn.s194068.

    CAS  Article  Google Scholar 

  39. 39.

    Liu CH, Chiu HC, Wu WC, Sahoo SL, Hsu CY. Novel lutein loaded lipid nanoparticles on porcine corneal distribution. J Ophthalmol. 2014;2014:304694. https://doi.org/10.1155/2014/304694.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Chaiyasan W, Srinivas SP, Tiyaboonchai W. Mucoadhesive chitosan-dextran sulfate nanoparticles for sustained drug delivery to the ocular surface. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics. 2013;29(2):200–7. https://doi.org/10.1089/jop.2012.0193.

    CAS  Article  Google Scholar 

  41. 41.

    Lim C, Kim DW, Sim T, Hoang NH, Lee JW, Lee ES, et al. Preparation and characterization of a lutein loading nanoemulsion system for ophthalmic eye drops. J Drug Deliv Sci Technol. 2016;36:168–74. https://doi.org/10.1016/j.jddst.2016.10.009.

    CAS  Article  Google Scholar 

  42. 42.

    Hazzah HA, Farid RM, Nasra MMA, Hazzah WA, El-Massik MA, Abdallah OY. Gelucire-based nanoparticles for curcumin targeting to oral mucosa: preparation, characterization, and antimicrobial activity assessment. J Pharm Sci. 2015;104(11):3913–24. https://doi.org/10.1002/jps.24590.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Shah SR, Parikh RH, Chavda JR, Sheth NR. Application of Plackett-Burman screening design for preparing glibenclamide nanoparticles for dissolution enhancement. Powder Technol. 2013;235:405–11. https://doi.org/10.1016/j.powtec.2012.10.055.

    CAS  Article  Google Scholar 

  44. 44.

    Shah SR, Parikh RH, Chavda JR, Sheth NR. Glibenclamide nanocrystals for bioavailability enhancement: formulation design, process optimization, and pharmacodynamic evaluation. J Pharm Innov. 2014;9(3):227–37. https://doi.org/10.1007/s12247-014-9189-y.

    Article  Google Scholar 

  45. 45.

    Shah S, Parmar B, Soniwala M, Chavda J. Design, optimization, and evaluation of lurasidone hydrochloride nanocrystals. AAPS PharmSciTech. 2015;17(5):1150–8. https://doi.org/10.1208/s12249-015-0449-z.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Ahmad I, Pandit J, Sultana Y, Mishra AK, Hazari PP, Aqil M. Optimization by design of etoposide loaded solid lipid nanoparticles for ocular delivery: characterization, pharmacokinetic and deposition study. Mater Sci Eng C. 2019;100:959–70. https://doi.org/10.1016/j.msec.2019.03.060.

    CAS  Article  Google Scholar 

  47. 47.

    Liu R, Liu Z, Zhang C, Zhang B. Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability. J Pharm Sci. 2012;101(10):3833–44. https://doi.org/10.1002/jps.23251.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263–71. https://doi.org/10.1208/s12248-010-9185-1.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Khare A, Singh I, Pawar P, Grover K. Design and evaluation of voriconazole loaded solid lipid nanoparticles for ophthalmic application. J Drug Deliv. 2016;2016:6590361. https://doi.org/10.1155/2016/6590361.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Khames A, Khaleel MA, El-Badawy MF, El-Nezhawy AOH. Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization. Int J Nanomed. 2019;14:2515–31. https://doi.org/10.2147/ijn.s190502.

    CAS  Article  Google Scholar 

  51. 51.

    Zhang W, Li X, Ye T, Chen F, Yu S, Chen J, et al. Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions. Int J Nanomed. 2014;9:4305–15. https://doi.org/10.2147/ijn.s63414.

    Article  Google Scholar 

  52. 52.

    Yadav M, Schiavone N, Guzman-Aranguez A, Giansanti F, Papucci L, de Lara MJP, et al. Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD). Drug Deliv Transl Res. 2020;10(4):919–44. https://doi.org/10.1007/s13346-020-00733-4.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Greenland S, Senn SJ, Rothman KJ, Carlin JB, Poole C, Goodman SN, et al. Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations. Eur J Epidemiol. 2016;31(4):337–50. https://doi.org/10.1007/s10654-016-0149-3.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Nimtrakul P, Tiyaboonchai W, Lamlertthon S. Amphotericin B loaded nanostructured lipid carriers for parenteral delivery: characterization, antifungal and in vitro toxicity assessment. Curr Drug Deliv. 2019;16(7):645–53. https://doi.org/10.2174/1567201816666190729145223.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Bhalekar M, Upadhaya P, Madgulkar A. Formulation and characterization of solid lipid nanoparticles for an anti-retroviral drug darunavir. Appl Nanosci. 2017;7(1–2):47–57. https://doi.org/10.1007/s13204-017-0547-1.

    CAS  Article  Google Scholar 

  56. 56.

    Morrison PWJ, Khutoryanskiy VV. Advances in ophthalmic drug delivery. Ther Deliv. 2014;5(12):1297–315. https://doi.org/10.4155/tde.14.75.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Moiseev RV, Morrison PWJ, Steele F, Khutoryanskiy VV. Penetration enhancers in ocular drug delivery. Pharmaceutics. 2019;11(7):321. https://doi.org/10.3390/pharmaceutics11070321.

    CAS  Article  PubMed Central  Google Scholar 

  58. 58.

    Deshkar S, Quazi N, Patil A, Poddar S. Effect of Gelucire 44/14 on fluconazole solid lipid nanoparticles: formulation, optimization and in vitro characterization. Drug Deliv Lett. 2016;5(3):173–87. https://doi.org/10.2174/221030310503160401121141.

    CAS  Article  Google Scholar 

  59. 59.

    Urbán-Morlán Z, Ganem-Rondero A, Melgoza-Contreras LM, Escobar-Chávez JJ, Nava-Arzaluz MG, Quintanar-Guerrero D. Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method. Int J Nanomed. 2010;5:611–20. https://doi.org/10.2147/ijn.s12125.

    Article  Google Scholar 

  60. 60.

    Shanmugam S, Baskaran R, Balakrishnan P, Thapa P, Yong CS, Yoo BK. Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein. Eur J Pharm Biopharm. 2011;79(2):250–7. https://doi.org/10.1016/j.ejpb.2011.04.012.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Sreekumar S, Goycoolea FM, Moerschbacher BM, Rivera-Rodriguez GR. Parameters influencing the size of chitosan-TPP nano- and microparticles. Sci Rep. 2018;8(1):4695. https://doi.org/10.1038/s41598-018-23064-4.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Noriega-Peláez EK, Mendoza-Muñoz N, Ganem-Quintanar A, Quintanar-Guerrero D. Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles. Drug Dev Ind Pharm. 2010;37(2):160–6. https://doi.org/10.3109/03639045.2010.501800.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Kushwaha AK, Vuddanda PR, Karunanidhi P, Singh SK, Singh S. Development and evaluation of solid lipid nanoparticles of raloxifene hydrochloride for enhanced bioavailability. Biomed Res Int. 2013;2013:584549. https://doi.org/10.1155/2013/584549.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Kuo Y-C, Chung J-F. Physicochemical properties of nevirapine-loaded solid lipid nanoparticles and nanostructured lipid carriers. Colloids Surf B. 2011;83(2):299–306. https://doi.org/10.1016/j.colsurfb.2010.11.037.

    CAS  Article  Google Scholar 

  65. 65.

    Chokshi NV, Khatri HN, Patel MM. Formulation, optimization, and characterization of rifampicin-loaded solid lipid nanoparticles for the treatment of tuberculosis. Drug Dev Ind Pharm. 2018;44(12):1975–89. https://doi.org/10.1080/03639045.2018.1506472.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3):348–60. https://doi.org/10.1208/s12248-010-9183-3.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Liu R, Liu Z, Zhang C, Zhang B. Gelucire44/14 as a novel absorption enhancer for drugs with different hydrophilicities: in vitro and in vivo improvement on transcorneal permeation. J Pharm Sci. 2011;100(8):3186–95. https://doi.org/10.1002/jps.22540.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    Li X, Nie SF, Kong J, Li N, Ju CY, Pan WS. A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers. Int J Pharm. 2008;363(1–2):177–82. https://doi.org/10.1016/j.ijpharm.2008.07.017.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Clayson K, Sandwisch T, Ma Y, Pavlatos E, Pan X, Liu J. Corneal hydration control during ex vivo experimentation using poloxamers. Curr Eye Res. 2020;45(2):111–7. https://doi.org/10.1080/02713683.2019.1663387.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. Bhagvanlal Kapoorchand Mody Government Pharmacy College, Rajkot, India

    Sunny Shah, Brijesh Bhanderi, Moinuddin Soniwala & Jayant Chavda

Authors
  1. Sunny Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brijesh Bhanderi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Moinuddin Soniwala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jayant Chavda
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the work.

Corresponding author

Correspondence to Sunny Shah.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 316 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Shah, S., Bhanderi, B., Soniwala, M. et al. Lutein-Loaded Solid Lipid Nanoparticles for Ocular Delivery: Statistical Optimization and Ex Vivo Evaluation. J Pharm Innov (2021). https://doi.org/10.1007/s12247-021-09537-6

Download citation

Keywords

  • Corneal permeation
  • Experimental designs
  • Lutein
  • Ocular delivery
  • Solid lipid nanoparticles
  • Statistical optimization