Skip to main content

Advertisement

Log in

Bemotrizinol-Loaded Carnauba Wax-Based Nanostructured Lipid Carriers for Sunscreen: Optimization, Characterization, and In vitro Evaluation

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Nanostructured lipid carriers (NLC) are aqueous dispersions of nanoparticles formed by solid and liquid lipids. In this study, NLC containing an organic UV filter, bemotrizinol, were developed for sunscreen formulation using carnauba wax and caprylic/capric triglycerides through ultrasonication technique. A Box-Behnken design was used to evaluate the influence of three variables on the particle size with the purpose of choosing the best system for further characterization. The particle size decreased as the surfactant concentration increased, reaching an average size of 122.4 ± 0.3 nm at 30 days of storage. Scanning electron microscopy showed intact and spherical particles. Thermal analysis and Fourier-transform infrared spectroscopy suggest that bemotrizinol was incorporated into the NLC. The X-ray diffraction showed a reduction in the crystallinity of the NLC. In vitro analysis indicated an improvement in the photoprotective activity of bemotrizinol when incorporated into NLC. These findings suggest a promising, stable, and biocompatible system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Cestari TF, de Oliveira FB, Boza JC. Considerations on photoprotection and skin disorders. Ann Dermatol Venereol. 2012;139:135–43. https://doi.org/10.1016/S0151-9638(12)70125-4.

    Article  Google Scholar 

  2. Young AR, Claveau J, Rossi AB. Ultraviolet radiation and the skin: photobiology and sunscreen photoprotection. J Am Acad Dermatol. 2017;76:100–9. https://doi.org/10.1016/j.jaad.2016.09.038.

    Article  CAS  Google Scholar 

  3. Sambandan DR, Ratner D. Sunscreens: an overview and update. J Am Acad Dermatol. 2011;64:748–58. https://doi.org/10.1016/j.jaad.2010.01.005.

    Article  CAS  PubMed  Google Scholar 

  4. Watson M, Holman DM, Maguire-Eisen M. Ultraviolet radiation exposure and its impact on skin cancer risk. Semin Oncol Nurs. 2016;32:241–54. https://doi.org/10.1016/j.soncn.2016.05.005.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jansen R, Wang SQ, Burnett M, Osterwalder U, Lim HW. Photoprotection: part I. Photoprotection by naturally occurring, physical, and systemic agents. J Am Acad Dermatol. 2013;69:853.e1–853.e12. https://doi.org/10.1016/j.jaad.2013.08.021.

    Article  CAS  Google Scholar 

  6. Cozzi AC, Perugini P, Gourion-Arsiquaud S. Comparative behavior between sunscreens based on free or encapsulated UV filters in term of skin penetration, retention and photo-stability. Eur J Pharm Sci. 2018;121:309–18. https://doi.org/10.1016/j.ejps.2018.06.001.

    Article  CAS  PubMed  Google Scholar 

  7. Heo S, Hwang HS, Jeong Y, Na K. Skin protection efficacy from UV irradiation and skin penetration property of polysaccharide-benzophenone conjugates as a sunscreen agent. Carbohydr Polym. 2018;195:534–41. https://doi.org/10.1016/j.carbpol.2018.05.010.

    Article  CAS  PubMed  Google Scholar 

  8. Al-Jamal MS, Griffith JL, Lim HW. Photoprotection in ethnic skin. Dermatol Sin. 2014;32:217–24. https://doi.org/10.1016/j.dsi.2014.09.001.

    Article  Google Scholar 

  9. González S, Fernández-Lorente M, Gilaberte-Calzada Y. The latest on skin photoprotection. Clin Dermatol. 2008;26:614–26. https://doi.org/10.1016/j.clindermatol.2007.09.010.

    Article  PubMed  Google Scholar 

  10. Morabito K, Shapley NC, Steeley KG, Tripathi A. Review of sunscreen and the emergence of non-conventional absorbers and their applications in ultraviolet protection. Int J Cosmet Sci. 2011;33:385–90. https://doi.org/10.1111/j.1468-2494.2011.00654.x.

    Article  CAS  PubMed  Google Scholar 

  11. Chatelain E, Gabard B. Photostabilization of butyl methoxydibenzoylmethane (avobenzone) and ethylhexyl methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), a new UV broadband filter. Photochem Photobiol. 2001;74:401–6.

    Article  CAS  Google Scholar 

  12. Cerqueira Coutinho C d S, dos Santos EP, Mansur CRE. Nanosystems in Photoprotection. J Nanosci Nanotechnol. 2015;15:9679–88. https://doi.org/10.1166/jnn.2015.10512.

    Article  CAS  Google Scholar 

  13. Gilbert E, Roussel L, Serre C, Sandouk R, Salmon D, Kirilov P, et al. Percutaneous absorption of benzophenone-3 loaded lipid nanoparticles and polymeric nanocapsules: a comparative study. Int J Pharm. 2016;504:48–58. https://doi.org/10.1016/j.ijpharm.2016.03.018.

    Article  CAS  PubMed  Google Scholar 

  14. Alvarez-Román R, Barré G, Guya RH, Fessi H. Biodegradable polymer nanocapsules containing a sunscreen agent: preparation and photoprotection. Eur J Pharm Biopharm. 2001;52:191–5. https://doi.org/10.1016/S0939-6411(01)00188-6.

    Article  PubMed  Google Scholar 

  15. Villalobos-Hernández JR, Müller-Goymann CC. Novel nanoparticulate carrier system based on carnauba wax and decyl oleate for the dispersion of inorganic sunscreens in aqueous media. Eur J Pharm Biopharm. 2005;60:113–22. https://doi.org/10.1016/j.ejpb.2004.11.002.

    Article  CAS  PubMed  Google Scholar 

  16. Nikolić S, Keck CM, Anselmi C, Müller RH. Skin photoprotection improvement: synergistic interaction between lipid nanoparticles and organic UV filters. Int J Pharm. 2011;414:276–84. https://doi.org/10.1016/j.ijpharm.2011.05.010.

    Article  CAS  PubMed  Google Scholar 

  17. Manaia EB, Kaminski RCK, Soares CP, Meneau F, Pulcinelli SH, Santilli CV, et al. Liquid crystalline formulations containing modified surface TiO 2 nanoparticles obtained by sol-gel process. J Sol-Gel Sci Technol. 2012;63:251–7. https://doi.org/10.1007/s10971-011-2673-7.

    Article  CAS  Google Scholar 

  18. Puglia C, Damiani E, Offerta A, Rizza L, Tirendi GG, Tarico MS, et al. Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies. Eur J Pharm Sci. 2014;51:211–7. https://doi.org/10.1016/j.ejps.2013.09.023.

    Article  CAS  PubMed  Google Scholar 

  19. Baccarin T, Mitjans M, Ramos D, Lemos-Senna E, Vinardell MP. Photoprotection by Punica granatum seed oil nanoemulsion entrapping polyphenol-rich ethyl acetate fraction against UVB-induced DNA damage in human keratinocyte (HaCaT) cell line. J Photochem Photobiol B Biol. 2015;153:127–36. https://doi.org/10.1016/j.jphotobiol.2015.09.005.

    Article  CAS  Google Scholar 

  20. Gutiérrez-Hernández JM, Escalante A, Murillo-Vázquez RN, Delgado E, González FJ, Toríz G. Use of Agave tequilana-lignin and zinc oxide nanoparticles for skin photoprotection. J Photochem Photobiol B Biol. 2016;163:156–61. https://doi.org/10.1016/j.jphotobiol.2016.08.027.

    Article  CAS  Google Scholar 

  21. De Oliveira CA, Peres DDA, Graziola F, Chacra NAB, De Araújo GLB, Flórido AC, et al. Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters. Eur J Pharm Sci. 2016;81:1–9. https://doi.org/10.1016/j.ejps.2015.09.016.

    Article  CAS  PubMed  Google Scholar 

  22. Lv X, Cong Z, Liu Z, Ma X, Xu M, Tian Y, et al. Improvement of the solubility, photostability, antioxidant activity and UVB photoprotection of trans-resveratrol by essential oil based microemulsions for topical application. J Drug Deliv Sci Technol. 2018;48:346–54. https://doi.org/10.1016/j.jddst.2018.10.017.

    Article  CAS  Google Scholar 

  23. Frizzo MS, Feuser PE, Berres PH, Ricci-Júnior E, Campos CEM, Costa C, et al. Simultaneous encapsulation of zinc oxide and octocrylene in poly (methyl methacrylate-co-styrene) nanoparticles obtained by miniemulsion polymerization for use in sunscreen formulations. Colloids Surf A Physicochem Eng Asp. 2019;561:39–46. https://doi.org/10.1016/j.colsurfa.2018.10.062.

    Article  CAS  Google Scholar 

  24. Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int J Pharm. 2009;366:170–84. https://doi.org/10.1016/j.ijpharm.2008.10.003.

    Article  CAS  PubMed  Google Scholar 

  25. Khurana S, Jain NK, Bedi PMS. Development and characterization of a novel controlled release drug delivery system based on nanostructured lipid carriers gel for meloxicam. Life Sci. 2013;93:763–72. https://doi.org/10.1016/j.lfs.2013.09.027.

    Article  CAS  PubMed  Google Scholar 

  26. Salminen H, Helgason T, Aulbach S, Kristinsson B, Kristbergsson K, Weiss J. Influence of co-surfactants on crystallization and stability of solid lipid nanoparticles. J Colloid Interface Sci. 2014;426:256–63. https://doi.org/10.1016/j.jcis.2014.04.009.

    Article  CAS  PubMed  Google Scholar 

  27. Jain P, Rahi P, Pandey V, Asati S, Soni V. Nanostructure lipid carriers: a modish contrivance to overcome the ultraviolet effects. Egypt J Basic Appl Sci. 2017;4:89–100. https://doi.org/10.1016/j.ejbas.2017.02.001.

    Article  Google Scholar 

  28. Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH. Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance. Int J Pharm. 2011;414:267–75. https://doi.org/10.1016/j.ijpharm.2011.05.008.

    Article  CAS  PubMed  Google Scholar 

  29. Abdel-Salam FS, Ammar HO, Elkheshen SA, Mahmoud AA. Anti-inflammatory sunscreen nanostructured lipid carrier formulations. J Drug Deliv Sci Technol. 2017;37:13–9. https://doi.org/10.1016/j.jddst.2016.10.014.

    Article  CAS  Google Scholar 

  30. Sala M, Diab R, Elaissari A, Fessi H. Lipid nanocarriers as skin drug delivery systems: properties, mechanisms of skin interactions and medical applications. Int J Pharm. 2018;535:1–17. https://doi.org/10.1016/j.ijpharm.2017.10.046.

    Article  CAS  PubMed  Google Scholar 

  31. Mansur JS, Breder MNR, Mansur MCD, Azulay RD. Determinação do fator de proteção solar por espectrofotometria. An Bras Dermatol. 1986;61:121–4.

    Google Scholar 

  32. Sayre RM, Agin PP, Levee GJ, Marlowe E. A comparison of in vivo and in vitro testing of sunscreening formulas. Photochem Photobiol. 1979;29:559–66.

    Article  CAS  Google Scholar 

  33. Thapa C, Ahad A, Aqil M, Imam SS, Sultana Y. Formulation and optimization of nanostructured lipid carriers to enhance oral bioavailability of telmisartan using Box–Behnken design. J Drug Deliv Sci Technol. 2018;44:431–9. https://doi.org/10.1016/j.jddst.2018.02.003.

    Article  CAS  Google Scholar 

  34. Aditya NP, Macedo AS, Doktorovova S, Souto EB, Kim S, Chang PS, et al. Development and evaluation of lipid nanocarriers for quercetin delivery: a comparative study of solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid nanoemulsions (LNE). LWT Food Sci Technol. 2014;59:115–21. https://doi.org/10.1016/j.lwt.2014.04.058.

    Article  CAS  Google Scholar 

  35. Gaba B, Fazil M, Khan S, Ali A, Baboota S, Ali J. Nanostructured lipid carrier system for topical delivery of terbinafine hydrochloride. Bull Fac Pharm, Cairo Univ. 2015;53:147–59. https://doi.org/10.1016/j.bfopcu.2015.10.001.

    Article  Google Scholar 

  36. Sato MR, Oshiro Junior JA, Machado RTA, de Souza PC, Campos DL, Pavan FR, et al. Nanostructured lipid carriers for incorporation of copper (II) complexes to be used against Mycobacterium tuberculosis. Drug Des Devel Ther. 2017;11:909–21. https://doi.org/10.2147/DDDT.S127048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Junyaprasert VB, Teeranachaideekul V, Souto EB, Boonme P, Müller RH. Q10-loaded NLC versus nanoemulsions: stability, rheology and in vitro skin permeation. Int J Pharm. 2009;377:207–14. https://doi.org/10.1016/j.ijpharm.2009.05.020.

    Article  CAS  PubMed  Google Scholar 

  38. Kovacevic A, Savic S, Vuleta G, Müller RH, Keck CM. Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure. Int J Pharm. 2011;406:163–72. https://doi.org/10.1016/j.ijpharm.2010.12.036.

    Article  CAS  PubMed  Google Scholar 

  39. Wissing SA, Müller RH. A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles. Int J Cosmet Sci. 2001;23:233–43. https://doi.org/10.1046/j.1467-2494.2001.00087.x.

    Article  CAS  PubMed  Google Scholar 

  40. Wang W, Chen L, Huang X, Shao A. Preparation and characterization of minoxidil loaded nanostructured lipid carriers. AAPS PharmSciTech. 2017;18:509–16. https://doi.org/10.1208/s12249-016-0519-x.

    Article  CAS  PubMed  Google Scholar 

  41. Rapalli VK, Kaul V, Waghule T, Gorantla S, Sharma S. Curcumin loaded nanostructured lipid carriers for enhanced skin retained topical delivery: optimization, scale-up, in-vitro characterization and assessment of ex-vivo skin deposition. Eur J Pharm Sci. 2020;152:105438. https://doi.org/10.1016/j.ejps.2020.105438.

    Article  CAS  PubMed  Google Scholar 

  42. Abla MJ, Banga AK. Formulation of tocopherol nanocarriers and in vitro delivery into human skin. Int J Cosmet Sci. 2014;36:239–46. https://doi.org/10.1111/ics.12119.

    Article  CAS  PubMed  Google Scholar 

  43. Pinto F, Fonseca LP, Souza S, Oliva A, de Barros DP. Topical distribution and efficiency of nanostructured lipid carriers on a 3D reconstructed human epidermis model. J Drug Deliv Sci Technol. 2020;101616:101616. https://doi.org/10.1016/j.jddst.2020.101616.

    Article  CAS  Google Scholar 

  44. Haque T, Crowther JM, Lane ME, Moore DJ. Chemical ultraviolet absorbers topically applied in a skin barrier mimetic formulation remain in the outer stratum corneum of porcine skin. Int J Pharm. 2016;510:250–4. https://doi.org/10.1016/j.ijpharm.2016.06.041.

    Article  CAS  PubMed  Google Scholar 

  45. Castelli F, Puglia C, Sarpietro MG, Rizza L, Bonina F. Characterization of indomethacin-loaded lipid nanoparticles by differential scanning calorimetry. Int J Pharm. 2005;304:231–8. https://doi.org/10.1016/j.ijpharm.2005.08.011.

    Article  CAS  PubMed  Google Scholar 

  46. Uprit S, Kumar Sahu R, Roy A, Pare A. Preparation and characterization of minoxidil loaded nanostructured lipid carrier gel for effective treatment of alopecia. Saudi Pharm J. 2013;21:379–85. https://doi.org/10.1016/j.jsps.2012.11.005.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Freitas CAS, Vieira ÍGP, Sousa PHM, Muniz CR, Gonzaga MLDC, Guedes MIF. Carnauba wax p-methoxycinnamic diesters: characterisation, antioxidant activity and simulated gastrointestinal digestion followed by in vitro bioaccessibility. Food Chem. 2016;196:1293–300. https://doi.org/10.1016/j.foodchem.2015.10.101.

    Article  CAS  PubMed  Google Scholar 

  48. Pradhan M, Singh D, Murthy SN, Singh MR. Design, characterization and skin permeating potential of fluocinolone acetonide loaded nanostructured lipid carriers for topical treatment of psoriasis. Steroids. 2015;101:56–63. https://doi.org/10.1016/j.steroids.2015.05.012.

    Article  CAS  PubMed  Google Scholar 

  49. Agrawal Y, Petkar KC, Sawant KK. Development, evaluation and clinical studies of acitretin loaded nanostructured lipid carriers for topical treatment of psoriasis. Int J Pharm. 2010;401:93–102. https://doi.org/10.1016/j.ijpharm.2010.09.007.

    Article  CAS  PubMed  Google Scholar 

  50. Sanad RA, AbdelMalak NS, Badawi AA. Formulation of a novel oxybenzone-loaded nanostructured lipid carriers (NLCs). AAPS PharmSciTech. 2010;11:1684–94. https://doi.org/10.1208/s12249-010-9553-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Imran M, Iqubal MK, Imtiyaz K, Saleem S, Mittal S, Rizvi MMA, et al. Topical nanostructured lipid carrier gel of quercetin and resveratrol: formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. Int J Pharm. 2020:119705. https://doi.org/10.1016/j.ijpharm.2020.119705.

  52. Li B, Ge ZQ. Nanostructured lipid carriers improve skin permeation and chemical stability of idebenone. AAPS PharmSciTech. 2012;13:276–83. https://doi.org/10.1208/s12249-011-9746-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tran TH, Ramasamy T, Truong DH, Choi HG, Yong CS, Kim JO. Preparation and characterization of fenofibrate-loaded nanostructured lipid carriers for oral bioavailability enhancement. AAPS PharmSciTech. 2014;15:1509–15. https://doi.org/10.1208/s12249-014-0175-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dan N. Compound release from nanostructured lipid carriers (NLCs). J Food Eng. 2016;171:37–43. https://doi.org/10.1016/j.jfoodeng.2015.10.005.

    Article  CAS  Google Scholar 

  55. Khosa A, Reddi S, Saha RN. Nanostructured lipid carriers for site-specific drug delivery. Biomed Pharmacother. 2018;103:598–613. https://doi.org/10.1016/j.biopha.2018.04.055.

    Article  CAS  PubMed  Google Scholar 

  56. Santiago RR, Silva KGDH, Santos ND, Genre J, Oliveira LVF, Silva AL, et al. Nanostructured lipid carriers containing amphotericin B: development, in vitro release assay, and storage stability. J Drug Deliv Sci Technol. 2018;48:372–82. https://doi.org/10.1016/j.jddst.2018.10.003.

    Article  CAS  Google Scholar 

  57. Motawea A, Abd El-Gawad HAEG, Borg T, Motawea M, Tarshoby M. The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration. Foot. 2019;40:14–21. https://doi.org/10.1016/j.foot.2019.03.007.

    Article  Google Scholar 

  58. Espinosa-Olivares MA, Delgado-Buenrostro NL, Chirino YI, Trejo-Marquez MA, Pascual-Bustamante S, Gnem-Rondero A. Nanostructured lipid carriers loaded with curcuminoids: physicochemical characterization, in vitro release, ex vivo skin penetration, stability and antioxidant activity. Eur J Pharm Sci. 2020:105533. https://doi.org/10.1016/j.ejps.2020.105533.

  59. Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54:S131–55. https://doi.org/10.1016/S0169-409X(02)00118-7.

    Article  PubMed  Google Scholar 

  60. Prado AH, Araújo VHS, Eloy JO, Fonseca-Santos B, Pereira-da-Silva MA, Peccinini RG, et al. Synthesis and characterization of nanostructured lipid nanocarriers for enhanced sun protection factor of Octyl p-methoxycinnamate. AAPS PharmSciTech. 2020;21:125. https://doi.org/10.1208/s12249-019-1547-0.

    Article  CAS  PubMed  Google Scholar 

  61. Tahir N, Madni A, Balasubramanian V, Rehman M, Correia A, Kashif PM, et al. Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications. Int J Pharm. 2017;533:156–68. https://doi.org/10.1016/j.ijpharm.2017.09.061.

    Article  CAS  PubMed  Google Scholar 

  62. Villalobos-Hernández JR, Müller-Goymann CC. Sun protection enhancement of titanium dioxide crystals by the use of carnauba wax nanoparticles: the synergistic interaction between organic and inorganic sunscreens at nanoscale. Int J Pharm. 2006;322:161–70. https://doi.org/10.1016/j.ijpharm.2006.05.037.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The study was financially supported by the PROPESQ-UEPB (4.03.00.005-400/2017-1), CNPq (453940/2014-5), and CAPES (Finance code 001).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to João A. Oshiro-Júnior or Bolívar P. G. L. Damasceno.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

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

Supplementary Material

Figure A.1

Predicted values versus observed values. (JPG 177 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Medeiros, T.S., Moreira, L.M.C.C., Oliveira, T.M.T. et al. Bemotrizinol-Loaded Carnauba Wax-Based Nanostructured Lipid Carriers for Sunscreen: Optimization, Characterization, and In vitro Evaluation. AAPS PharmSciTech 21, 288 (2020). https://doi.org/10.1208/s12249-020-01821-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-020-01821-x

KEY WORDS

Navigation