PHARMACOKINETICS AND ORAL DELIVERY OF POLYMETHOXYLATED FLAVONES

Abstract

Polymethylated flavones are constituents of many herbs and edible plants in nature. Their broad spectrum of pharmacological activities such as anti-inflammatory, anti-cancer, anti-diabetic, anti-bacterial, anti-fungal, blood thinning and neuro-protective effects have been reported extensively. To further evaluate the medicinal potentials of three polymethylated flavones, namely tangeretin (TAN), apigenin trimethyl ether (ATE), and luteolin tetramethyl ether (LTE), their pharmacokinetic profiles were assessed in Sprague-Dawley rats. Aqueous solubility has been identified a major barrier to their oral bioavailability. Subsequently, self-microemulsifying drug delivery system (SMEDDS) was developed and characterized. In vivo evaluation found that the oral delivery of ATE and LTE was substantially enhanced by SMEDDS. Moreover, abundant tissue distribution of TMF was also confirmed. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or the herbs contain ATE. The results obtain from this PhD study will facilitate further medicinal explorations on TAN, ATE, and LTE.