Yanghuan Ye1, Tianpeng Zhang1, Wan Li1, Hua Sun1, Danyi Lu1, Baojian Wu2, Xingwang Zhang3. 1. Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China. 2. Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China. bj.wu@hotmail.com. 3. Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China. pharmazxw@gmail.com.
Abstract
PURPOSE: Oral therapy with raloxifene (RXF), an amphiphobic drug for remedy of the postmenopausal osteoporosis and estrogen-dependent breast cancer, is less effective due to its poor bioavailability (2% or so). This work aimed to devise mesoporous carbon nanospheres (MCNs) for oral delivery of RXF and evaluate their performance in bioavailability enhancement and lymphatic transport. METHODS: Glucose-based MCNs were fabricated by hydrothermal reaction followed by high-temperature activation. RXF-loaded MCNs (RXF-MCNs) were prepared by solvent-diffusion/high-pressure homogenization and stabilized by phospholipid. RXF-MCNs were fully characterized by particle size, morphology, in vitro drug release and metabolism, in vivo pharmacokinetics and lymphatic transport, and ex vivo fluorescent imaging. RESULTS: The prepared RXF-MCNs were 230 nm around in particle size, showing high entrapment efficiency (95.35%) and satisfactory physical stability. The oral bioavailability of RXF was enhanced by 2.07 folds through MCNs compared with RXF suspensions in rats. It was shown that reduced intestinal metabolism due to entrapment into MCNs, active transcellular uptake and increased lymphatic transport were responsible for enhanced bioavailability as a result of transport improvement. CONCLUSIONS: The results suggest that MCNs are suitable nanocarriers for oral delivery of poorly bioavailable RXF.
PURPOSE: Oral therapy with raloxifene (RXF), an amphiphobic drug for remedy of the postmenopausal osteoporosis and estrogen-dependent breast cancer, is less effective due to its poor bioavailability (2% or so). This work aimed to devise mesoporous carbon nanospheres (MCNs) for oral delivery of RXF and evaluate their performance in bioavailability enhancement and lymphatic transport. METHODS:Glucose-based MCNs were fabricated by hydrothermal reaction followed by high-temperature activation. RXF-loaded MCNs (RXF-MCNs) were prepared by solvent-diffusion/high-pressure homogenization and stabilized by phospholipid. RXF-MCNs were fully characterized by particle size, morphology, in vitro drug release and metabolism, in vivo pharmacokinetics and lymphatic transport, and ex vivo fluorescent imaging. RESULTS: The prepared RXF-MCNs were 230 nm around in particle size, showing high entrapment efficiency (95.35%) and satisfactory physical stability. The oral bioavailability of RXF was enhanced by 2.07 folds through MCNs compared with RXF suspensions in rats. It was shown that reduced intestinal metabolism due to entrapment into MCNs, active transcellular uptake and increased lymphatic transport were responsible for enhanced bioavailability as a result of transport improvement. CONCLUSIONS: The results suggest that MCNs are suitable nanocarriers for oral delivery of poorly bioavailable RXF.
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