Oral and Lymphatic Delivery of Paclitaxel via Lipid Nanocapsules

Abstract

Paclitaxel (Ptx) is a potent anticancer drug, especially in breast and ovarian cancers. However, orally administered Ptx presents a major therapeutic challenge because of its low bioavailability. In addition, an adjuvant consisting of Cremophor？？ EL and dehydrated alcohol is used in current clinical formulations of Ptx, which causes serious side effects. The side effects of Cremophor？？ EL include hypersensitivity reactions, nephrotoxicity, and neurotoxicity. Therefore, this study prepared lipid nanocapsules (LNCs) containing Ptx to reduce its toxicity and improve bioavailability. The LNCs were characterized using droplet size distribution, zeta potential, drug encapsulation efficiency, stability, differential scanning calorimetry, field emission-transmission electron microscopy, and in vitro release tests. The reference (Ptx) solution and LNCs containing Ptx were orally administered (12 mg/kg) to rats. The plasma and the mesenteric and axillary lymph nodes were obtained, and the concentrations of Ptx in these tissues were measured to compare and evaluate the pharmacokinetics and lymphatic delivery of Ptx. The mean droplet size, zeta potential, and encapsulation efficiency of the optimized Ptx-LNCs were approximately 87.6±6.2 nm, -4.0±0.4 mV, and 90.5±7.8%, respectively. The in vitro release profiles of the prepared Ptx-LNCs were affected by the pH of the dissolution media. Based on in vivo studies, the bioavailability of orally administered Ptx in LNCs was significantly (p<0.05) improved by approximately 2-fold compared to the reference solution. The prepared Ptx-LNCs also showed significantly (p<0.05) higher lymphatic targeting efficiencies than the reference solution. Based on these results, we conclude that the prepared Ptx-LNCs could be a good candidate as an effective oral formulation of Ptx.