Facilitating gastrointestinal solubilisation and enhanced oral absorption of SN38 using a molecularly complexed...

SN38 (7-ethyl-10-hydroxycamptothecin) is a highly potent anti-cancer compound. However, it is poorly soluble in pharmaceutically acceptable excipients, thus the direct formulation and delivery are restricted. The current study focused on lipid-based formulation design to enable oral delivery of SN38 at high doses and at therapeutic levels. The pH dependent ionisation property of SN38 was utilised to form a molecular complex with the cationic surfactant, oleylamine and this increased (>200-fold) solubility/loading in Labrasol (the optimally determined lipid carrier). A SN38 loaded silica-lipid hybrid (SN38-SLH) particle delivery system was prepared by lyophilisation of mesoporous silica nanoparticle stabilised lipid emulsions. The subsequent free-flowing, SLH solid dosage form contained high loading levels of molecularly dispersed SN38 (5%w/w) and significantly enhanced in vitro dissolution in simulated gastrointestinal media. Furthermore, SN38 was chemically stable for at least 12months at 25°C. Orally dosed pharmacokinetics in a rat model demonstrated a 176% increase in SN38 blood plasma exposure in comparison with a raw drug suspension and a significant increase in the period where therapeutic levels are established. SN38-SLH shows potential for enabling injection-to-oral transformation in cancer chemotherapy.