Polymeric nanoparticles for topical delivery of alpha and beta arbutin: preparation and characterization

  • Nursyafiqah Sahrum Ayumi
  • Shariza Sahudin
  • Zahid Hussain
  • Mumtaz Hussain
  • Nor Hayati Abu Samah
Original Article
First Online:
  • 22 Downloads

Abstract

To investigate the use of chitosan nanoparticles (CS-TPP-NPs) as carriers for α- and β-arbutin. In this study, CS-TPP-NPs containing α- and β-arbutin were prepared via the ionic cross-linking of CS and TPP and characterized for particle size, zeta potential, and dispersity index. The entrapment efficiency and loading capacity of various β-arbutin concentrations (0.1, 0.2, 0.4, 0.5, and 0.6%) were also investigated. SEM, TEM FTIR, DSC and TGA analyses of the nanoparticles were performed to further characterize the nanoparticles. Finally, stability and release studies were undertaken to ascertain further the suitability of the nanoparticles as a carrier system for α- and β-arbutin. Data obtained clearly indicates the potential for use of CS-TPP-NPs as a carrier for the delivery of α- and β-arbutin. The size obtained for the alpha nanoparticles (α-arbutin CSNPs) ranges from 147 to 274 d.nm, with an increase in size with increasing alpha arbutin concentration. β-arbutin nanoparticles (β-arbutin CSNPs) size range was from 211.1 to 284 dn.m. PdI for all nanoparticles remained between 0.2–0.3 while the zeta potential was between 41.6–52.1 mV. The optimum encapsulation efficiency and loading capacity for 0.4% α-arbutin CSNPs were 71 and 77%, respectively. As for β-arbutin, CSNP optimum encapsulation efficiency and loading capacity for 0.4% concentration were 68 and 74%, respectively. Scanning electron microscopy for α-arbutin CSNPs showed a more spherical shape compared to β-arbutin CSNPs where rod-shaped particles were observed. However, under transmission electron microscopy, the shapes of both α- and β-arbutin CSNP nanoparticles were spherical. The crystal phase identification of the studied samples was carried out using X-ray diffraction (XRD), and the XRD of both α and β-arbutin CSNPs showed to be more crystalline in comparison to their free form. FTIR spectra showed intense characteristic peaks of chitosan appearing at 3438.3 cm−1 (-OH stretching), 2912 cm−1 (-CH stretching), represented 1598.01 cm−1 (-NH2) for both nanoparticles. Stability studies conducted for 90 days revealed that both α- and β-arbutin CSNPs were stable in solution. Finally, release studies of both α- and β-arbutin CSNPs showed a significantly higher percentage release in comparison to α- and β-arbutin in their free form. Chitosan nanoparticles demonstrate considerable promise as a carrier system for α- and β-arbutin, the use of which is anticipated to improve delivery of arbutin through the skin, in order to improve its efficacy as a whitening agent.

Keywords

Chitosan nanoparticles Whitening agent β-arbutin α-arbutin Ionic gelation 
This is a preview of subscription content, log in to check access.

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Salata O. Applications of nanoparticles in biology and medicine. J. Nano Biotechnology. 2004;2:3.Google Scholar
  2. 2.
    Seo D-H, Jung J-H, Lee J-E, Jeon E-J, Kim W, Park C-S. Biotechnological production of arbutins (α- and β-arbutins), skin-lightening agents, and their derivatives. Appl Biochem Biotechnol. 2012;95:1417–25.Google Scholar
  3. 3.
    Wang A-C, Cheng S-H, Sheu C, Kwan C-C. Simultaneous determination of five whitening agents by ion-pair reversed-phase high performance liquid chromatography. Int J Appl Sci Eng. 2011;9(4):287–99.Google Scholar
  4. 4.
    Dudhani AR, Kosaraju SL. Bioadhesive chitosan nanoparticles: preparation and characterization. J. Carbohydr Polym. 2010;81:243–51.CrossRefGoogle Scholar
  5. 5.
    Gan Q, Wang T. Chitosan nanoparticle as protein delivery carrier—systematic examination of fabrication conditions for efficient loading and release. J Colloid Surface B. 2007;59(1):24–34.CrossRefGoogle Scholar
  6. 6.
    Elsaesser A, Howard CV. Toxicology of nanoparticles. Int J Nanomedicine. 2012;64:129–37.Google Scholar
  7. 7.
    Leelapornpisid P, Leesawat P, Natakarnkitkul S, Rattanapanadda P. Application of chitosan for preparation of arbutin nanoparticles as skin whitening. J Metals, Mater Miner. 2010;20(3):101–5.Google Scholar
  8. 8.
    Sugimoto K, Nishimura T, Nomura K, Sugimoto K, Kuriki T. Inhibitory effects of α-arbutin on melanin. Synthesis in cultured human melanoma cells and a three dimensional human skin model. Bio Pharm Bull. 2004;32(3):367–73.Google Scholar
  9. 9.
    Anitha A, Maya S, Deepa N, Chennazhi KP, Nair SV, Jayakumar R. Curcumin-loaded N,O-carboxymethyl chitosan nanoparticles for cancer drug delivery. J. Biomater. Sci. 2012;23(11):1381–400.Google Scholar
  10. 10.
    Pati F, Adhikari B, Dhara S. Development of chitosan & tripolyphosphate fibers through pH dependent ionotropic gelation. J Carbohydrate Res. 2011;346(2582–2588)Google Scholar
  11. 11.
    Janes KA, Fresneau MP, Marazuela A, Fabra A, Alonso MJ. Chitosan nanoparticles as delivery systems for doxorubicin. J Control Release. 2001;73(2–3):255–67.CrossRefPubMedGoogle Scholar
  12. 12.
    Liu C-Q, Deng L, Zhang P, Zhang S-R, Liu L, Xu T, et al. Screening of high α-arbutin producing strains and production of α-arbutin by fermentation. J Microb Biotechnol. 2013;29(8):1391–8.CrossRefGoogle Scholar
  13. 13.
    Arezou G, Soleiman M, Fatemeh T, Farid T. Synthesis and optimization of chitosan nanoparticles: potential applications in nanomedicine and biomedical engineering. J Intern Med. 2014;5(3):156–61.Google Scholar
  14. 14.
    Yassin EB, Anwer MK, Mowafy HA, Elbagory IM, Bayomi MA, Alsarra IA. Optimization of 5-fluorouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. Int J Med Sci. 2010;7:398–408.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhao L-M, Shi L-E, Zhang Z-L, Chen J-M, Shi D-D, Yang J, et al. Preparation and application of chitosan nanoparticles and nanofibers. Braz J Chem. 2011;28(3):353–62.CrossRefGoogle Scholar
  16. 16.
    Manoj KS, Sunil KP, Alok M, Neha R, Chitosan RS. A novel excipient in pharmaceutical formulation: a review. Int J Pharma Sci and Research. 2017:2266–77.Google Scholar
  17. 17.
    Alia ME, Lamprecht A. Spray freeze drying as an alternative technique for lyophilization of polymeric and lipid-based nanoparticles. Int J Pharm. 2017;516:170–7.CrossRefGoogle Scholar
  18. 18.
    Se KK, Niranjan R. Enzymatic production and biological activities of chitosan oligosaccharides (COS): a review. Carbohydr Polym. 2005;62:357–68.Google Scholar
  19. 19.
    Papadimitriou S, Bikiaris D, Avgoustakis K, Karavas E, Georgarakis M. Chitosan nanoparticles loaded with dorzolamide and pramipexole. Carbohydr Polym. 2008;73:44–54.CrossRefGoogle Scholar
  20. 20.
    Van der Lubben IM, Verhoef JC, Borchard G, Junginger HE. Chitosan for mucosal vaccination. Adv Drug Deliv Rev. 2001;52(2):139–44.CrossRefPubMedGoogle Scholar
  21. 21.
    ClaraM, RuoL, GianlucaC.Chitosan nanoparticles as therapeutic protein nanocarriers: the effect of pH on particle formation and encapsulation efficiency. Volume 34: 9, pp. 1538–1545(8) (2013).Google Scholar
  22. 22.
    Kazuhisa Sugimoto, Takahisa Nishimura, Koji Nomura, Kenji Sugimoto, and TakashiKuriki. Syntheses of arbutin-a-glycosides and a comparison of their inhibitory effects with those of a-arbutin and arbutin on human tyrosinase. Chem Pharm Bull51(7) 798—801 (2003).Google Scholar
  23. 23.
    Anarjan N, Jafarizadeh-Malmiri H, Nehdi IA, Sbihi HM, Al-Resayes SI, Tan CP. Effects of homogenization process parameters on physicochemical properties of astaxanthin nanodispersions prepared using a solvent diffusion technique. Int J Nanomedicine. 2015:1109.Google Scholar
  24. 24.
    Antonio R, Massimiliano B, Paolo BB, Bellicha AC. Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm. 2013;455(1–2):219–28.Google Scholar
  25. 25.
    Ghadiria M, Fatemi S, Vatanara A, Doroudb D, Najafabadib AR, Darabib M, et al. Loading hydrophilic drug in solid lipid media as nanoparticles: statistical modeling of entrapment efficiency and particle size. J Pharma. 2012;424:128–37.Google Scholar
  26. 26.
    Sivakumar SM. Pharmaceutical aspects of chitosan polymer. Int J Pharm and Tech. 2013:6–12.Google Scholar
  27. 27.
    Singla AK, Chawla M. Chitosan: some pharmaceutical and biological aspects. J Pharm Pharmacol. 2001;53:1047–67.CrossRefPubMedGoogle Scholar
  28. 28.
    Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100(1):5–28.CrossRefPubMedGoogle Scholar
  29. 29.
    Illum L. Nanoparticulate systems for delivery of drugs: a real improvement over simple systems. IntJ Pharma Sci. 2007;96:473.Google Scholar
  30. 30.
    Shaha SM, Ashtikarb M, Jaina AS, Makhijac DT, Nikamd Y, Guded RP, et al. Chitosan, and liposomes: a skin penetration study. Int J Pharm. 2015;490:391–403.CrossRefGoogle Scholar
  31. 31.
    Takeuchi H, Yamamoto H, Kawashima Y. Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev. 2001;47(1):39–54.CrossRefPubMedGoogle Scholar
  32. 32.
    Takeuchi H, Yamamoto H, Niwa T, Hino T, Kawashima Y. Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes. Pharm Res. 1996;13(6):896–901.CrossRefPubMedGoogle Scholar
  33. 33.
    Rejinold NS, Muthunarayanan M, Chennazhi KP, Nair SV, Jayakumar R. 5-Fluorouracil loaded fibrinogen nanoparticles for cancer drug delivery applications. Int J Biol Macromol. 2011;48(1):98–105.CrossRefPubMedGoogle Scholar
  34. 34.
    Hussain Z, Katas H, Amin MCIM, Kumolosasi E, Buang F, Sahudin S. Self-assembled polymeric nanoparticles for percutaneous co-delivery of hydrocortisone/hydroxytyrosol: an ex vivo and in vivo study using an NC/Nga mouse model. Int J Pharm. 2013;444:109–19.CrossRefPubMedGoogle Scholar
  35. 35.
    Nash RA, Haegar BE. Zeta potential in the development of pharmaceutical suspensions. Int. J Pharm Sci. 1996;Google Scholar
  36. 36.
    Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems—a review (part 1). J Pharm Res. 2013;12(2):255–64.Google Scholar
  37. 37.
    Havrdovaa M, Polakova K, Skopalik J, Vujtek M, Mokda A, Homolkova M, et al. Field emission scanning electron microscopy (FE-SEM) as an approach for nanoparticle detection inside. Cell. 2014:149–54.Google Scholar
  38. 38.
    Janes KA, Calvo P, Alonso MJ. Polysaccharide colloidal particles as delivery systems macromolecules. Adv Drug Deliv Rev. 2001;47(1):83–97.CrossRefPubMedGoogle Scholar
  39. 39.
    Janes KA, Alonso M. Depolymerized chitosan nanoparticles for protein delivery: preparation and characterization. Inter. J Appl Polym Sci. 2003;88:2769–76.CrossRefGoogle Scholar
  40. 40.
    R.V.Contri, L.A.Fiel, N.Alnasif,, A.R.Pohlmann, S.S.Guterres, M.Schafer Korting. Skin penetration and dermal tolerability of acrylic nanocapsules: influence of the surface charge and a chitosan gel used as vehicleInter J Pharma Vol 507, Issues 1–2, Pages 12–20, (2016).Google Scholar
  41. 41.
    Rajan M, Raj V. Encapsulation, characterisation and in-vitro release of anti-tuberculosis drug using chitosan poly ethylene glycol nanoparticles. Int J Pharm Pharm Sci. 2012;4(4):255–9.Google Scholar
  42. 42.
    Agnihotri S, Nadagouda MN, Aminabhavi TM. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100(1):5, 5–28.CrossRefPubMedGoogle Scholar
  43. 43.
    Suedina M.L.Silva, Carla R.C.Braga, Marcus V.L.Fook, Application of infrared spectroscopy to analysis of chitosan/clay nanocomposites J. Infrared Spectroscopy Materials Science, Eng Technol ,1–21(2011).Google Scholar
  44. 44.
    Schmid-Wendtner MH, Korting HC. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol. 2006;19:296–302.CrossRefPubMedGoogle Scholar
  45. 45.
    Senel S, McClure SJ. Potential applications of chitosan in veterinary medicine. Adv Drug Deliv Rev. 2004:23–32.Google Scholar
  46. 46.
    Goldstein A, Soroka Y, Frusic Zlotkin M, Popov I, Koh R. High resolution SEM imaging of nanoparticles in cells and tissues. J Microsc. 2014;256:237–47.CrossRefPubMedGoogle Scholar
  47. 47.
    Tarek A. Ahmed, Bader M Aljaeid.Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery J. Pharm Drug Devel Ther, 10483–507 (2016).Google Scholar
  48. 48.
    Thandapani Gomathia, P.N. Sudhaa, JAK Florence,Jayachandran Venkatesanc, Sukumaran Anil. Fabrication of letrozole formulation using chitosan nanoparticles through ionic gelation method. Int J Biol Macromol104 ,1820–1832 (2017).Google Scholar
  49. 49.
    Van der Lubben IM, Verhoef JC, van Aelst AC, Borchard G, Junginger HE. Chitosan microparticles for oral vaccination: preparation, characterization and preliminary in vivo uptake studies in murine Peyer’s patches. JBiomaterials. 2001;22(7):687–94.CrossRefGoogle Scholar
  50. 50.
    Baldrick P. The safety of chitosan as a pharmaceutical excipient. J Regul Toxicol Pharmacol. 2010;56(3):290–9.CrossRefGoogle Scholar
  51. 51.
    Chang ML, Chang C–M. Simultaneous HPLC determination of hydrophilic whitening agents in cosmetic products. J Pharm Biomed Anal. 2003;33:617–26.CrossRefPubMedGoogle Scholar
  52. 52.
    Felt O, Buri P, Gurny R. Chitosan: a unique polysaccharide for drug delivery. Drug Dev Ind Pharm. 1998;24:979–93.CrossRefPubMedGoogle Scholar
  53. 53.
    Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Deliv Rev. 2006;58:1688–713.CrossRefPubMedGoogle Scholar
  54. 54.
    Wang JJ, Zeng ZW, Xiao RZ. Recent advances of chitosan nanoparticles as drug carriers. Int J Nanomedicine. 2011;6:765–74.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Yangchao Luo, Boce Zhang, Monica Whent, Liangli Lucy Yu, Qin Wang. Preparation and characterization of zein/chitosan complex for encapsulation of α-tocopherol, and its in vitro controlled release study. Colloids and Surfaces B: Biointerfaces85 145–152 (2011).Google Scholar
  56. 56.
    Wang Y-W, Jou C-H, Hung C-C, Yang M-C. Cellular fusion and whitening effect of a chitosan derivative coated liposome. Colloids Surf B: Biointerfaces. 2012;90:169–76.CrossRefPubMedGoogle Scholar
  57. 57.
    Palmer BC, DeLouise LA. Nanoparticle-enabled transdermal drug delivery systems for enhanced dose control and tissue targeting. J Investig Dermatol. 2007;127:1701–12.CrossRefGoogle Scholar
  58. 58.
    Avonto C, Wang Y-H, Avula B, Khan IA. Investigation of the instability of alpha and beta-arbutin. J Cosmet Sci. 2014;  https://doi.org/10.1055/s-0034-1382659.
  59. 59.
    Cui F, Qian F, Yin C. Chitosan graft copolymer nanoparticles for protein drug delivery: preparation and characterization. Int J Pharma. 2006;316:154–61.CrossRefGoogle Scholar
  60. 60.
    EunsunL., SangJ. P., JaeH. L., MinS. K., Chun-H. K. Preparation of chitosan/TPP nanoparticles and their physical and biological properties. J Pharm Sci11:166–167(2016).Google Scholar
  61. 61.
    Aydm STR, Pulat M. 5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: evaluation of controlled release kinetics. JNanomater. 2012:1–10.Google Scholar
  62. 62.
    Papadimitriou S, Bikiaris D. Novel self-assembled core–shell nanoparticles based on crystalline amorphous moieties of aliphatic copolyesters for efficient controlled drug release. J Control Release. 2009;138:177–84.CrossRefPubMedGoogle Scholar
  63. 63.
    Ko H-H, Chiang Y-C, Tsai M-H, Liang C-J, Hsu L-F, Li S-Y, et al. Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: role of MAPK and Akt pathways. J Ethnopharmacol. 2014;151:386–93.CrossRefPubMedGoogle Scholar
  64. 64.
    Hussain Z, Sahudin S. Preparation, characterisation and colloidal stability of chitosan tripolyphosphate nanoparticles: optimisation of formulation and process parameters. Int J Pharm Pharm Sci. 2016;8(3):297–308.Google Scholar
  65. 65.
    Prego C, Garcia M, Torres D, Alonso M. Transdermal nano molecular chitosan drug delivery. J Control Release. 2005;101:151.CrossRefPubMedGoogle Scholar
  66. 66.
    Dhakar RC, Maurya SD, Saluja V. From formulation variables to drug entrapment efficiency of microspheres a technical review. J Drug Deliv Ther. 2012;2(6):128–33.Google Scholar

Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  • Nursyafiqah Sahrum Ayumi
    • 1
  • Shariza Sahudin
    • 1
  • Zahid Hussain
    • 1
  • Mumtaz Hussain
    • 1
  • Nor Hayati Abu Samah
    • 1
  1. 1.Department of Pharmaceutics, Faculty of PharmacyUniversiti Teknologi MaraSelangorMalaysia

Personalised recommendations