International Journal of Nanomedicine (Jul 2019)

Preparation and evaluation of tacrolimus-loaded thermosensitive solid lipid nanoparticles for improved dermal distribution

  • Kang JH,
  • Chon J,
  • Kim YI,
  • Lee HJ,
  • Oh DW,
  • Lee HG,
  • Han CS,
  • Kim DW,
  • Park CW

Journal volume & issue
Vol. Volume 14
pp. 5381 – 5396

Abstract

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Ji-Hyun Kang*,1 Jinmann Chon*,2 Young-Il Kim,1 Hyo-Jung Lee,1 Dong-Won Oh,1 Hong-Goo Lee,1 Chang-Soo Han,1 Dong-Wook Kim,3 Chun-Woong Park11College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 2School of Medicine, Kyung Hee University, Seoul, Republic of Korea; 3Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea*These authors contributed equally to this workBackground: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty.Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention.Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations.Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin.Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.Keywords: tacrolimus, thermosensitive, solid lipid nanoparticle, FT-IR imaging, atopic dermatitis, dermal delivery

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