Cyproterone Acetate Loading to Lipid Nanoparticles for Topical Acne Treatment: Particle Characterisation and Skin Uptake
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- Štecová, J., Mehnert, W., Blaschke, T. et al. Pharm Res (2007) 24: 991. doi:10.1007/s11095-006-9225-9
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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.
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.
With particulate systems topical CPA treatment may be an additional therapeutic option for acne and other diseases of the pilosebaceous unit.
Key wordscyproterone acetate lipid particles nanostructured lipid carriers parelectric spectroscopy pharmacological effects skin absorption
bovine serum albumin
concentration of drug specifically deplacing 3H-DHT by 50%
ethylenediamine tetraacetic acid
fetal calf serum
glyceraldehyde 3-phosphate dehydrogenase
mouse fibroblasts cell line GR+/29+
maximum particles size of 95% of the particles
nanostructured lipid carrier(s); M (Miglyol® 812), O (oleic acid) added as indicated to the lipid component
polymerase chain reaction
photon correlation spectroscopy
rotation per hour
solid lipid nanoparticle
immortalised sebocyte line
arithmetic mean value