Skip to main content

Advertisement

SpringerLink
Log in

HPMC/PVP Dissolving Microneedles: a Promising Delivery Platform to Promote Trans-Epidermal Delivery of Alpha-Arbutin for Skin Lightening

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

Abstract

Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 μg/cm2/h and 74.24 μg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 μg and 312.23 μg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Saeedi M, Eslamifar M, Khezri K. Kojic acid applications in cosmetic and pharmaceutical preparations. Biomedicine & Pharmacotherapy. 2019;110:582–93. https://doi.org/10.1016/j.biopha.2018.12.006.

    Article  CAS  Google Scholar 

  2. Desmedt B, Courselle P, De Beer JO, Rogiers V, Grosber M, Deconinck E, et al. Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe. J Eur Acad Dermatol Venereol. 2016;30(6):943–50. https://doi.org/10.1111/jdv.13595.

    Article  CAS  PubMed  Google Scholar 

  3. Couteau C, Coiffard L. Overview of skin whitening agents: drugs and cosmetic products. Cosmetics. 2016;3(3). https://doi.org/10.3390/cosmetics3030027.

  4. Migas P, Krauze-Baranowska M. The significance of arbutin and its derivatives in therapy and cosmetics. Phytochem Lett. 2015;13:35–40. https://doi.org/10.1016/j.phytol.2015.05.015.

    Article  CAS  Google Scholar 

  5. Sccs, Degen GH. Opinion of the Scientific Committee on Consumer safety (SCCS)—opinion on the safety of the use of α-arbutin in cosmetic products. Regul Toxicol Pharmacol. 2016;74:75–6. https://doi.org/10.1016/j.yrtph.2015.11.008.

    Article  CAS  PubMed  Google Scholar 

  6. Won J, Park J. Improvement of arbutin trans-epidermal delivery using radiofrequency microporation. 2014.

  7. Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438–70. https://doi.org/10.3390/pharmaceutics7040438.

    Article  CAS  PubMed  Google Scholar 

  8. Mahato R. Chapter 13—microneedles in drug delivery. In: Mitra AK, Cholkar K, Mandal A, editors. Emerging nanotechnologies for diagnostics, drug delivery and medical devices. Boston: Elsevier; 2017. p. 331–53.

    Google Scholar 

  9. Pamornpathomkul B, Ngawhirunpat T, Tekko IA, Vora L, McCarthy HO, Donnelly RF. Dissolving polymeric microneedle arrays for enhanced site-specific acyclovir delivery. Eur J Pharm Sci. 2018;121:200–9. https://doi.org/10.1016/j.ejps.2018.05.009.

    Article  CAS  PubMed  Google Scholar 

  10. Simon GA, Maibach HI. The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantitative observations—an overview. Skin Pharmacol Appl Ski Physiol. 2000;13(5):229–34. https://doi.org/10.1159/000029928.

    Article  CAS  Google Scholar 

  11. Touitou E, Meidan VM, Horwitz E. Methods for quantitative determination of drug localized in the skin. J Control Release. 1998;56(1–3):7–21.

    Article  CAS  Google Scholar 

  12. Cilurzo F, Minghetti P, Sinico C. Newborn pig skin as model membrane in in vitro drug permeation studies: a technical note. AAPS PharmSciTech. 2007;8(4):E94-E. https://doi.org/10.1208/pt0804094.

    Article  Google Scholar 

  13. Davies DJ, Ward RJ, Heylings JR. Multi-species assessment of electrical resistance as a skin integrity marker for in vitro percutaneous absorption studies. Toxicol In Vitro. 2004;18(3):351–8. https://doi.org/10.1016/j.tiv.2003.10.004.

    Article  CAS  PubMed  Google Scholar 

  14. El-Say KM. Maximizing the encapsulation efficiency and the bioavailability of controlled-release cetirizine microspheres using Draper-Lin small composite design. Drug Des Dev Ther. 2016;10:825–39. https://doi.org/10.2147/dddt.S101900.

    Article  CAS  Google Scholar 

  15. Machekposhti SA, Soltani M, Najafizadeh P, Ebrahimi SA, Chen P. Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid. J Controlled Release. 2017;261:87–92. https://doi.org/10.1016/j.jconrel.2017.06.016.

    Article  CAS  Google Scholar 

  16. Larrañeta E, Moore J, Vicente-Pérez EM, Gonzalez Vazquez P, Lutton R, David Woolfson A, et al. A proposed model membrane and test method for microneedle insertion studies. 2014.

  17. Yao G, Quan G, Lin S, Peng T, Wang Q, Ran H, et al. Novel dissolving microneedles for enhanced transdermal delivery of levonorgestrel: in vitro and in vivo characterization. Int J Pharm. 2017;534(1–2):378–86. https://doi.org/10.1016/j.ijpharm.2017.10.035.

    Article  CAS  PubMed  Google Scholar 

  18. Structural characterization of inclusion complex of arbutin.pdf. https://doi.org/10.4314/tjpr.v15i10.22.

  19. Larrañeta E, Henry M, Irwin NJ, Trotter J, Perminova AA, Donnelly RF. Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications. Carbohydr Polym. 2018;181:1194–205. https://doi.org/10.1016/j.carbpol.2017.12.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. LaFountaine JS, Prasad LK, Brough C, Miller DA, McGinity JW, Williams RO 3rd. Thermal processing of PVP- and HPMC-based amorphous solid dispersions. AAPS PharmSciTech. 2016;17(1):120–32. https://doi.org/10.1208/s12249-015-0417-7.

    Article  CAS  PubMed  Google Scholar 

  21. Baghel S, Cathcart H, O'Reilly NJ. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci. 2016;105(9):2527–44. https://doi.org/10.1016/j.xphs.2015.10.008.

    Article  CAS  PubMed  Google Scholar 

  22. Zhang M, Ma Y, Wang Z, Han Z, Gao W, Gu Y. Optimizing molecular weight of octyl chitosan as drug carrier for improving tumor therapeutic efficacy. Oncotarget. 2017;8(38):64237–49. https://doi.org/10.18632/oncotarget.19452.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kariduraganavar MY, Kittur AA, Kamble RR. Chapter 1—polymer synthesis and processing. In: Kumbar SG, Laurencin CT, Deng M, editors. Natural and synthetic biomedical polymers. Oxford: Elsevier; 2014. p. 1–31.

    Google Scholar 

  24. Tritt-Goc J, Kowalczuk J, Pislewski N. Hydration of hydroxypropylmethyl cellulose: effects of pH and molecular mass. Acta Physica Polonica A - Acta Phys Pol A. 2006;108. https://doi.org/10.12693/APhysPolA.108.197.

  25. Sarkar N, Walker LC. Hydration—dehydration properties of methylcellulose and hydroxypropylmethylcellulose. Carbohydr Polym. 1995;27(3):177–85. https://doi.org/10.1016/0144-8617(95)00061-B.

    Article  CAS  Google Scholar 

  26. Chen CP, Hsieh CM, Tsai T, Yang JC, Chen CT. Optimization and evaluation of a chitosan/hydroxypropyl methylcellulose hydrogel containing toluidine blue O for antimicrobial photodynamic inactivation. Int J Mol Sci. 2015;16(9):20859–72. https://doi.org/10.3390/ijms160920859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mojumdar EH, Pham QD, Topgaard D, Sparr E. Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum. Sci Rep. 2017;7(1):15712. https://doi.org/10.1038/s41598-017-15921-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Verdier-Sevrain S, Bonte F. Skin hydration: a review on its molecular mechanisms. J Cosmet Dermatol. 2007;6(2):75–82. https://doi.org/10.1111/j.1473-2165.2007.00300.x.

    Article  PubMed  Google Scholar 

  29. Shabbir M, Ali S, Raza M, Sharif A, Akhtar MF, Manan A, et al. Effect of hydrophilic and hydrophobic polymer on in vitro dissolution and permeation of bisoprolol fumarate through transdermal patch. Acta Pol Pharm. 2017;74:187–97.

    CAS  PubMed  Google Scholar 

  30. Grubauer G, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res. 1989;30(3):323–33.

    CAS  PubMed  Google Scholar 

  31. Menon GK, Feingold KR, Elias PM. Lamellar body secretory response to barrier disruption. J Investig Dermatol. 1992;98(3):279–89. https://doi.org/10.1111/1523-1747.ep12497866.

    Article  CAS  PubMed  Google Scholar 

  32. Gupta J, Gill HS, Andrews SN, Prausnitz MR. Kinetics of skin resealing after insertion of microneedles in human subjects. J Control Release. 2011;154(2):148–55. https://doi.org/10.1016/j.jconrel.2011.05.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We would like to thank Miss Pichsinee Choomung, Mr. Pitpiboon Srisantisuk, and Miss Thitipanchaya Panya for assistance with research and Dr. John Tigue for proofreading.

Funding

The research was supported by the Thailand Research Funds (RTA6180003) and the Research and Creative Fund, Faculty of Pharmacy, Silpakorn University.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Pharmaceutical Development of Green Innovations Group (PDGIG), Department of Pharmaceutical Technology, Silpakorn University, Nakhon Pathom, 73000, Thailand

    Nway Nway Aung, Tanasait Ngawhirunpat, Theerasak Rojanarata, Prasopchai Patrojanasophon & Praneet Opanasopit

  2. Thai Traditional Medicine College, Rajamangala University of Technology Thanyaburi, Thanyaburi, Pathum Thani, 12130, Thailand

    Boonnada Pamornpathomkul

Authors
  1. Nway Nway Aung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tanasait Ngawhirunpat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Theerasak Rojanarata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prasopchai Patrojanasophon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Praneet Opanasopit
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Boonnada Pamornpathomkul
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boonnada Pamornpathomkul.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aung, N.N., Ngawhirunpat, T., Rojanarata, T. et al. HPMC/PVP Dissolving Microneedles: a Promising Delivery Platform to Promote Trans-Epidermal Delivery of Alpha-Arbutin for Skin Lightening. AAPS PharmSciTech 21, 25 (2020). https://doi.org/10.1208/s12249-019-1599-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-019-1599-1

KEY WORDS

Search

Navigation