Cyproterone acetate loading to lipid nanoparticles for topical acne treatment: particle characterisation and skin uptake.
OBJECTIVE
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.


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.


CONCLUSIONS
With particulate systems topical CPA treatment may be an additional therapeutic option for acne and other diseases of the pilosebaceous unit.
Stecová
Jana
J
Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2-4, D-14195, Berlin, Germany.
Mehnert
Wolfgang
W
Blaschke
Tobias
T
Kleuser
Burkhard
B
Sivaramakrishnan
Ramadurai
R
Zouboulis
Christos C
CC
Seltmann
Holger
H
Korting
Hans Christian
HC
Kramer
Klaus D
KD
Schäfer-Korting
Monika
M
D000152:Acne Vulgaris / Q000188:drug therapy*; D000279:Administration, Cutaneous; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017373:Cyproterone Acetate / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D009570:Nitriles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D011944:Receptors, Androgen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013696:Temperature; D013997:Time Factors
D000726:Androgen Antagonists; D007093:Imidazoles; D008055:Lipids; D009570:Nitriles; D011944:Receptors, Androgen; C086458:RU 58841; D017373:Cyproterone Acetate