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

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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.

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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

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Acknowledgement

Financial support of the Deutsche Forschungsgemeinschaft, FG 463 (SCHA 382, KR 1696), is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Straße 2-4, D-14195, Berlin, Germany

    Jana Štecová, Wolfgang Mehnert, Burkhard Kleuser & Monika Schäfer-Korting

  2. Institut für Physik, Freie Universität Berlin, Berlin, Germany

    Tobias Blaschke, Ramadurai Sivaramakrishnan & Klaus D. Kramer

  3. Dermatologische Klinik, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany

    Christos C. Zouboulis & Holger Seltmann

  4. Dermatologische Klinik, Ludwig-Maximilians-Universität, München, Germany

    Hans Christian Korting

Authors
  1. Jana Štecová
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  2. Wolfgang Mehnert
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  3. Tobias Blaschke
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  7. Holger Seltmann
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  8. Hans Christian Korting
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  10. Monika Schäfer-Korting
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Correspondence to Monika Schäfer-Korting.

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Štecová, J., Mehnert, W., Blaschke, T. et al. Cyproterone Acetate Loading to Lipid Nanoparticles for Topical Acne Treatment: Particle Characterisation and Skin Uptake. Pharm Res 24, 991–1000 (2007). https://doi.org/10.1007/s11095-006-9225-9

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  • DOI: https://doi.org/10.1007/s11095-006-9225-9

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