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KMID : 0370220210650050375
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Yakhak Hoeji
2021 Volume.65 No. 5 p.375 ~ p.385
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Oral and Lymphatic Delivery of Paclitaxel via Lipid Nanocapsules
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Tran Phuong
Jang Ji-Hun
Jeong Seung-Hyun
Lee Yong-Bok
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Abstract
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Paclitaxel (Ptx) is a potent anticancer drug, especially in breast and ovarian cancers. However, orallyadministered Ptx presents a major therapeutic challenge because of its low bioavailability. In addition, an adjuvantconsisting of Cremophor® EL and dehydrated alcohol is used in current clinical formulations of Ptx, which causes seriousside 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 andaxillary lymph nodes were obtained, and the concentrations of Ptx in these tissues were measured to compare and evaluatethe pharmacokinetics and lymphatic delivery of Ptx. The mean droplet size, zeta potential, and encapsulation efficiency ofthe optimized Ptx-LNCs were approximately 87.6±6.2 nm, -4.0±0.4 mV, and 90.5±7.8%, respectively. The in vitro releaseprofiles of the prepared Ptx-LNCs were affected by the pH of the dissolution media. Based on in vivo studies, thebioavailability of orally administered Ptx in LNCs was significantly (p<0.05) improved by approximately 2-fold comparedto the reference solution. The prepared Ptx-LNCs also showed significantly (p<0.05) higher lymphatic targeting efficienciesthan the reference solution. Based on these results, we conclude that the prepared Ptx-LNCs could be a good candidateas an effective oral formulation of Ptx.
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KEYWORD
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Paclitaxel, Lipid nanocapsule, Lymphatic delivery, Pharmacokinetics
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