Skip to main content

Advertisement

Log in

Development of transdermal vitamin D3 (VD3) delivery system using combinations of PLGA nanoparticles and microneedles

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Although vitamin D3 (VD3), which is the main form of vitamin D, can be produced in human skin under the sunlight, vitamin D deficiency emerged as a major public health problem worldwide. Mainly, oral supplements or vitamin D-fortified foods are distributed to help supplementation of vitamin D. However, those oral methods are limitedly supplied in the Middle East countries, and oral absorption has low efficiency due to many barriers and various changes of conditions along the route. Then, it is recommended to take them every day in order to maintain the adequate serum level of vitamin D. Alternatively, transdermal delivery system could provide a convenient way to get sustained supplement of vitamin D by its advantages like avoiding first-pass effect of the liver and providing release for long periods of time. In this study, we introduced transdermal delivery system for sustained vitamin D release using coating microneedles that easily pierce the skin layer with enough mechanical strength and allow the localization of drugs within the dermal region. According to the experimental results, poly (lactic-co-glycolic acid) (PLGA) successfully encapsulated VD3 as a nanoparticle form with appropriate properties for transdermal delivery such as size distribution, skin compatibility, and effective release of encapsulated compound. Finally, PVD3 layers coated on solid microneedles were completely dissolved into intradermal region in porcine skin model and revealed better performance for VD3 release into plasma compared to ointment base transdermal method.

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
Fig. 9

Similar content being viewed by others

References

  1. Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999;96(4):507–15. https://doi.org/10.1016/S0092-8674(00)80655-8.

    Article  CAS  PubMed  Google Scholar 

  2. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010;95(2):471–8. https://doi.org/10.1210/jc.2009-1773.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lehmann B, Meurer M. Vitamin D metabolism. Dermatol Ther. 2010;23(1):2–12. https://doi.org/10.1111/j.1529-8019.2009.01286.x.

    Article  PubMed  Google Scholar 

  4. Luo Y, Teng Z, Wang Q. Development of zein nanoparticles coated with carboxymethyl chitosan for encapsulation and controlled release of vitamin D3. J Agric Food Chem. 2012;60(3):836–43. https://doi.org/10.1021/jf204194z.

    Article  CAS  PubMed  Google Scholar 

  5. Al Anouti F, Thomas J, Abdel-Wareth L, Rajah J, Grant WB, Haq A. Vitamin D deficiency and sun avoidance among university students at Abu Dhabi, United Arab Emirates. Dermato-endocrinology. 2011;3(4):235–9. https://doi.org/10.4161/derm.3.4.16881.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008;3(5):1535–41. https://doi.org/10.2215/CJN.01160308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Alsaqr A, Rasoully M, Musteata FM. Investigating transdermal delivery of vitamin D3. AAPS PharmSciTech. 2015;16(4):963–72. https://doi.org/10.1208/s12249-015-0291-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. N’Da DD. Prodrug strategies for enhancing the percutaneous absorption of drugs. Molecules. 2014;19(12):20780–807. https://doi.org/10.3390/molecules191220780.

    Article  PubMed  Google Scholar 

  9. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261–8. https://doi.org/10.1038/nbt.1504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Haham M, Ish-Shalom S, Nodelman M, Duek I, Segal E, Kustanovich M, et al. Stability and bioavailability of vitamin D nanoencapsulated in casein micelles. Food Funct. 2012;3(7):737–44. https://doi.org/10.1039/c2fo10249h.

    Article  CAS  PubMed  Google Scholar 

  11. Abbasi A, Emam-Djomeh Z, Mousavi MA, Davoodi D. Stability of vitamin D(3) encapsulated in nanoparticles of whey protein isolate. Food Chem. 2014;143:379–83. https://doi.org/10.1016/j.foodchem.2013.08.018.

    Article  CAS  PubMed  Google Scholar 

  12. Manosroi A, Chankhampan C, Manosroi W, Manosroi J. Transdermal absorption enhancement of papain loaded in elastic niosomes incorporated in gel for scar treatment. Eur J Pharm Sci. 2013;48(3):474–83. https://doi.org/10.1016/j.ejps.2012.12.010.

    Article  CAS  PubMed  Google Scholar 

  13. Baek SH, Shin JH, Kim YC. Drug-coated microneedles for rapid and painless local anesthesia. Biomed Microdevices. 2017;19(1):2. https://doi.org/10.1007/s10544-016-0144-1.

    Article  PubMed  Google Scholar 

  14. Donnelly RF, Morrow DI, Fay F, Scott CJ, Abdelghany S, Singh RR, et al. Microneedle-mediated intradermal nanoparticle delivery: potential for enhanced local administration of hydrophobic pre-formed photosensitisers. Photodiagn Photodyn Ther. 2010;7(4):222–31. https://doi.org/10.1016/j.pdpdt.2010.09.001.

    Article  CAS  Google Scholar 

  15. Kim YC, Park JH, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012;64(14):1547–68. https://doi.org/10.1016/j.addr.2012.04.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Prausnitz MR. Microneedles for transdermal drug delivery. Adv Drug Deliv Rev. 2004;56(5):581–7. https://doi.org/10.1016/j.addr.2003.10.023.

    Article  CAS  PubMed  Google Scholar 

  17. Lee SG, Jeong JH, Lee KM, Jeong KH, Yang H, Kim M, et al. Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule. Int J Nanomedicine. 2014;9:289–99. https://doi.org/10.2147/IJN.S54529.

    PubMed  Google Scholar 

  18. Ramadan E, Borg T, Abdelghani G, Saleh NM. Transdermal microneedle-mediated delivery of polymeric lamivudine-loaded nanoparticles. J Pharm Technol Drug Res. 2016;5(1):1. https://doi.org/10.7243/2050-120X-5-1.

    Article  Google Scholar 

  19. Rao JP, Geckeler KE. Polymer nanoparticles: preparation techniques and size-control parameters. Prog Polym Sci. 2011;36(7):887–913. https://doi.org/10.1016/j.progpolymsci.2011.01.001.

    Article  CAS  Google Scholar 

  20. Panyam J, Dali MM, Sahoo SK, Ma W, Chakravarthi SS, Amidon GL, et al. Polymer degradation and in vitro release of a model protein from poly(D,L-lactide-co-glycolide) nano- and microparticles. J Control Release. 2003;92(1–2):173–87. https://doi.org/10.1016/S0168-3659(03)00328-6.

    Article  CAS  PubMed  Google Scholar 

  21. Kim SJ, Shin JH, Noh JY, Song CS, Kim YC. Development of the novel coating formulations for skin vaccination using stainless steel microneedle. Drug Deliv Transl Res. 2016;6(5):486–97. https://doi.org/10.1007/s13346-016-0321-z.

    Article  PubMed  Google Scholar 

  22. Kim YC, Quan FS, Compans RW, Kang SM, Prausnitz MR. Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. J Control Release. 2010;142(2):187–95. https://doi.org/10.1016/j.jconrel.2009.10.013.

    Article  CAS  PubMed  Google Scholar 

  23. Gill HS, Prausnitz MR. Coated microneedles for transdermal delivery. J Control Release. 2007;117(2):227–37. https://doi.org/10.1016/j.jconrel.2006.10.017.

    Article  CAS  PubMed  Google Scholar 

  24. Seok H, Noh JY, Lee DY, Kim SJ, Song CS, Kim YC. Effective humoral immune response from a H1N1 DNA vaccine delivered to the skin by microneedles coated with PLGA-based cationic nanoparticles. J Control Release. 2017; https://doi.org/10.1016/j.jconrel.2017.04.027.

  25. Caldorera-Moore M, Guimard N, Shi L, Roy K. Designer nanoparticles: incorporating size, shape and triggered release into nanoscale drug carriers. Expert Opin Drug Deliv. 2010;7(4):479–95. https://doi.org/10.1517/17425240903579971.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cegnar M, Kos J, Kristl J. Cystatin incorporated in poly(lactide-co-glycolide) nanoparticles: development and fundamental studies on preservation of its activity. Eur J Pharm Sci. 2004;22(5):357–64. https://doi.org/10.1016/j.ejps.2004.04.003.

    Article  CAS  PubMed  Google Scholar 

  27. Coulman SA, Anstey A, Gateley C, Morrissey A, McLoughlin P, Allender C, et al. Microneedle mediated delivery of nanoparticles into human skin. Int J Pharm. 2009;366(1–2):190–200. https://doi.org/10.1016/j.ijpharm.2008.08.040.

    Article  CAS  PubMed  Google Scholar 

  28. Desai ND, Singh PP, Amin PD, Jain SP. Stability-indicating LC method for assay of cholecalciferol. Chromatographia. 2009;69(3–4):385–8. https://doi.org/10.1365/s10337-008-0914-x.

    Article  CAS  Google Scholar 

  29. Budhian A, Siegel SJ, Winey KI. Production of haloperidol-loaded PLGA nanoparticles for extended controlled drug release of haloperidol. J Microencapsul. 2005;22(7):773–85. https://doi.org/10.1080/02652040500273753.

    Article  CAS  PubMed  Google Scholar 

  30. Yang YY, Chia HH, Chung TS. Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. J Control Release. 2000;69(1):81–96. https://doi.org/10.1016/S0168-3659(00)00291-1.

    Article  CAS  PubMed  Google Scholar 

  31. Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3(3):1377–97. https://doi.org/10.3390/polym3031377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hossein-nezhad A, Holick MF, editors. Vitamin D for health: a global perspective. Mayo Clinic Proceedings. Elsevier; 2013.

  33. Li X, Kong X, Zhang Z, Nan K, Li L, Wang X, et al. Cytotoxicity and biocompatibility evaluation of N,O-carboxymethyl chitosan/oxidized alginate hydrogel for drug delivery application. Int J Biol Macromol. 2012;50(5):1299–305. https://doi.org/10.1016/j.ijbiomac.2012.03.008.

    Article  CAS  PubMed  Google Scholar 

  34. Archana D, Singh BK, Dutta J, Dutta P. In vivo evaluation of chitosan–PVP–titanium dioxide nanocomposite as wound dressing material. Carbohydr Polym. 2013;95(1):530–9. https://doi.org/10.1016/j.carbpol.2013.03.034.

    Article  CAS  PubMed  Google Scholar 

  35. Kim YC, Song JM, Lipatov AS, Choi SO, Lee JW, Donis RO, et al. Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch. Eur J Pharm Biopharm. 2012;81(2):239–47. https://doi.org/10.1016/j.ejpb.2012.03.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ammar H, Ghorab M, El-Nahhas S, Kamel R. Evaluation of chemical penetration enhancers for transdermal delivery of aspirin. Asian J Pharm Sci. 2007;2:96–105.

    CAS  Google Scholar 

  37. Godin B, Touitou E. Transdermal skin delivery: predictions for humans from in vivo, ex vivo and animal models. Adv Drug Deliv Rev. 2007;59(11):1152–61. https://doi.org/10.1016/j.addr.2007.07.004.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Matching Fund Project of KAIST-Kustar Institute (Project No. N11160038) and by the Ministry of Science and ICT (Project No. NRF-2014M3A9E4064580).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yeu-Chun Kim.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, HG., Gater, D.L. & Kim, YC. Development of transdermal vitamin D3 (VD3) delivery system using combinations of PLGA nanoparticles and microneedles. Drug Deliv. and Transl. Res. 8, 281–290 (2018). https://doi.org/10.1007/s13346-017-0460-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-017-0460-x

Keywords

Navigation