title: Nanosuspensions Containing Oridonin/HP-β-Cyclodextrin Inclusion Complexes for Oral Bioavailability Enhancement via Improved Dissolution and Permeability.
abstract: Chemotherapy via oral route of anticancer drugs offers much convenience and compliance to patients. However, oral chemotherapy has been challenged by limited absorption due to poor drug solubility and intestinal efflux. In this study, we aimed to develop a nanosuspension formulation of oridonin (Odn) using its cyclodextrin inclusion complexes to enhance oral bioavailability. Nanosuspensions containing Odn/2 hydroxypropyl-β-cyclodextrin inclusion complexes (Odn-CICs) were prepared by a solvent evaporation followed by wet media milling technique. The nanosuspensions were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and dissolution. The resulting nanosuspensions were approximately 313.8 nm in particle size and presented a microcrystal morphology. Nanosuspensions loading Odn-CICs dramatically enhanced the dissolution of Odn. Further, the intestinal effective permeability of Odn was markedly enhanced in the presence of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and poloxamer. Bioavailability studies showed that nanosuspensions with Odn-CICs can significantly promote the oral absorption of Odn with a relative bioavailability of 213.99% (Odn suspensions as reference). Odn itself possesses a moderate permeability and marginal intestinal metabolism. Thus, the enhanced bioavailability for Odn-CIC nanosuspensions can be attributed to improved dissolution and permeability by interaction with absorptive epithelia and anti-drug efflux. Nanosuspensions prepared from inclusion complexes may be a promising approach for the oral delivery of anticancer agents.
authors.affiliation: Institute of Animal Husbandry and Veterinary, Henan Academy of Agricultural Sciences, Zhengzhou, 450008, China.|Division of Pharmaceutics, School of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutics, School of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China.
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Animal Husbandry and Veterinary, Henan Academy of Agricultural Sciences, Zhengzhou, 450008, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Division of Pharmaceutics, School of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou, 510632, China. bj.wu@hotmail.com.
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
authors.affiliation: Institute of Animal Husbandry and Veterinary, Henan Academy of Agricultural Sciences, Zhengzhou, 450008, China. szhvet@163.com.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Shi
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000379:methods; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013535:Suspensions / Q000737:chemistry* / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D045786:Diterpenes, Kaurane; D013535:Suspensions; D047392:beta-Cyclodextrins; C011959:oridonin; D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: bioavailability; cyclodextrin inclusion complexes; dissolution; nanosuspensions; oridonin