title: Glucose-Based Mesoporous Carbon Nanospheres as Functional Carriers for Oral Delivery of Amphiphobic Raloxifene: Insights into the Bioavailability Enhancement and Lymphatic Transport.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Yanghuan
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Li
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
authors.forename: Danyi
authors.initials: D
authors.lastname: Lu
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China. bj.wu@hotmail.com.
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China. pharmazxw@gmail.com.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000502:physiology; D002244:Carbon / Q000737:chemistry*; D002460:Cell Line; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005947:Glucose / Q000737:chemistry*; D008196:Lymph / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D054118:Nanospheres / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004337:Drug Carriers; D010743:Phospholipids; D020849:Raloxifene Hydrochloride; D002244:Carbon; D005947:Glucose
keywords: bioadhesion; bioavailability; lymphatic transport; mesoporous carbons; raloxifene