Studies on the anti-psoriatic activity of gossypol and its derivatives followed by pre-formulation and formulation studies of gossypol into a topical dosage form

Gossypol, a natural anti-inflammatory compound, has been studied extensively since the discovery of its in vivo male antifertility activity in the late
1960s and has since shown anti-viral, anti-parasitic and anti-tumour activity.
Psoriasis is a multifactorial skin condition characterised by benign keratinocyte
hyper-proliferation, skin inflammation, defective keratinisation, altered dermal
vasculature and insufficient anti-oxidant activity. In this study the in vitro
anti-psoriatic activity of gossypol and its derivatives was evaluated using an
anti-proliferative assay and an anti-oxidant assay (Dodou et al 2005). In the
anti-proliferative study, the sensitivity of an HPV-16 keratinocyte cell line to
each compound was determined using an MTT viability assay. The compounds
that showed increased inhibition against keratinocyte proliferation were subsequently tested for their anti-oxidant effect against iron/ascorbate dependent
lipid peroxidation, using the thiobarbituric acid (TBA) test. Racemic gossypol
(GI50 ¼ 5.4 0.03 M) and its enantiomers were the most potent compounds
against the proliferation of HPV-16 keratinocytes, followed by the half-Schiff’s
bases (GI50 ¼ 15–50 M), racemic gossypolone (GI50¼ 47.3 M) and the bisSchiff’s bases (GI50> 100 M). A comparison was made with the data from
the MTT assays on HPV-16 keratinocyte cell lines using methotrexate
(GI50 ¼ 148 M) and dithranol (GI50 ¼ 0.58 M). All tested compounds showed
similar anti-oxidant activity (IC50 17 M) and were more potent than the
positive control propyl gallate (IC70¼ 100 M). Pre-formulation and formulation studies were then conducted on racemic gossypol, which was the most
active compound according to the biological assays. The pre-formulation
studies included saturation solubility in hydrophilic and lipophilic vehicles,
compatibility with excipients, partition co-efficient over pH range 2–8, and
physicochemical stability in solution under extreme light, heat, acidic, basic