Pharmaceutical Research

, Volume 24, Issue 5, pp 991–1000

Cyproterone Acetate Loading to Lipid Nanoparticles for Topical Acne Treatment: Particle Characterisation and Skin Uptake

  • Jana Štecová
  • Wolfgang Mehnert
  • Tobias Blaschke
  • Burkhard Kleuser
  • Ramadurai Sivaramakrishnan
  • Christos C. Zouboulis
  • Holger Seltmann
  • Hans Christian Korting
  • Klaus D. Kramer
  • Monika Schäfer-Korting
Research Paper

DOI: 10.1007/s11095-006-9225-9

Cite this article as:
Štecová, J., Mehnert, W., Blaschke, T. et al. Pharm Res (2007) 24: 991. doi:10.1007/s11095-006-9225-9
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Abstract

Purpose

Topical cyproterone acetate (CPA) treatment of skin diseases should reduce side effects currently excluding the use in males and demanding contraceptive measures in females. To improve skin penetration of the poorly absorbed drug, we intended to identify the active moiety and to load it to particulate carrier systems.

Materials and Methods

CPA metabolism in human fibroblasts, keratinocytes and a sebocyte cell line as well as androgen receptor affinity of native CPA and the hydrolysis product cyproterone were determined. CPA 0.05% loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), a nanoemulsion and micropheres were characterized for drug-particle interaction and CPA absorption using human skin ex-vivo.

Results

Native CPA proved to be the active agent. Application of CPA attached to SLN increased skin penetration at least four-fold over the uptake from cream and nanoemulsion. Incorporation into the lipid matrix of NLC and microspheres resulted in a 2–3-fold increase in CPA absorption. Drug amounts within the dermis were low with all preparations. No difference was seen in the penetration into intact and stripped skin.

Conclusion

With particulate systems topical CPA treatment may be an additional therapeutic option for acne and other diseases of the pilosebaceous unit.

Key words

cyproterone acetate lipid particles nanostructured lipid carriers parelectric spectroscopy pharmacological effects skin absorption 

Abbreviations

BSA

bovine serum albumin

CP

cyproterone

CPA

cyproterone acetate

DHT

dihydrotestosterone

EC50

concentration of drug specifically deplacing 3H-DHT by 50%

EDTA

ethylenediamine tetraacetic acid

FCS

fetal calf serum

GAPDH

glyceraldehyde 3-phosphate dehydrogenase

GR+/29+

mouse fibroblasts cell line GR+/29+

LD95%

maximum particles size of 95% of the particles

mRNA

messenger-RNA

MS

microspheres

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NLC

nanostructured lipid carrier(s); M (Miglyol® 812), O (oleic acid) added as indicated to the lipid component

NE

nanoemulsion

PBS

phosphate-buffered saline

PCR

polymerase chain reaction

PCS

photon correlation spectroscopy

PI

polydispersity index

PS

parelectric spectroscopy

rph

rotation per hour

SD

standard deviation

SLN

solid lipid nanoparticle

SZ95

immortalised sebocyte line

f0

dipole mobility

Δɛ

dipole density

\(\overline{{\text{x}}}\)

arithmetic mean value

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jana Štecová
    • 1
  • Wolfgang Mehnert
    • 1
  • Tobias Blaschke
    • 2
  • Burkhard Kleuser
    • 1
  • Ramadurai Sivaramakrishnan
    • 2
  • Christos C. Zouboulis
    • 3
  • Holger Seltmann
    • 3
  • Hans Christian Korting
    • 4
  • Klaus D. Kramer
    • 2
  • Monika Schäfer-Korting
    • 1
  1. 1.Institut für PharmazieFreie Universität BerlinBerlinGermany
  2. 2.Institut für PhysikFreie Universität BerlinBerlinGermany
  3. 3.Dermatologische KlinikCharité-Universitätsmedizin Berlin Campus Benjamin FranklinGermany
  4. 4.Dermatologische KlinikLudwig-Maximilians-Universität MünchenGermany

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