Novel pH-Sensitive Lipid-Polymer Composite Microspheres of 10-Hydroxycamptothecin Exhibiting Colon-Specific Biodistribution and Reduced Systemic Absorption

Novel lipid-polymer composite microspheres (LP-MS) were prepared by combining pH-sensitive polymer Eudragit S100 with solid lipid Compritol 888 ATO for colonic delivery of 10-hydroxycamptothecin (HCPT), and pH-dependent controlled drug release has been achieved. The colon-specific biodistribution and uptake by the mucosal tissue were examined using coumarin-6-marked LP-MS. It is proved that good in vitro-in vivo relationship has been achieved, with more drugs being delivered to colon and a higher drug level was maintained for a long period. Moreover, in vivo bioavailability of LP-MS was evaluated with conventional enteric microspheres (enteric MS) as reference. After administration of LP-MS, systemic absorption of HCPT was greatly reduced, with area under the curve from 0 to 24 h (AUC_0 -24h, 2.186 ± 0.27) being significantly lower than that of enteric MS group (6.352 ± 0.696). In conclusion, the novel pH-sensitive LP-MS has potential for colon-specific drug delivery.