title: Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan.
abstract: The objective of this study was to construct a new in situ gel system based on the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407 hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed potassium ion concentration - dependent erosion characteristics which ensured slow erosion in aqueous environment containing potassium ion at the physiological level. Loading with ketorolac tromethamine influenced erosion, drug release and thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine showed suitable gelation temperature (near 35°C) and in vitro sustained release profiles. Pharmacokinetic study of intranasal CPH containing 15% ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability (68.8 ± 23.3%) and prolonged mean residence time (8.8 ± 3.5h) in comparison with the intranasal solution group (24.8 ± 13.8%, 3.9 ± 0.6h). Nasal ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the safety of CPH for intranasal use. All results suggested the potential of CPH as a new sustained - release platform for the intranasal delivery of ketorolac tromethamine.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China; Department of Clinical Pharmacy, Institute for Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China; School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China; School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Zheshuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacy, Institute for Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China. Electronic address: liuyu@fudan.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D002351:Carrageenan / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000737:chemistry; D007477:Ions / Q000737:chemistry; D020911:Ketorolac Tromethamine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D007477:Ions; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020911:Ketorolac Tromethamine; D002351:Carrageenan; D011188:Potassium
keywords: Bioavailability; Carrageenan; In situ hydrogel; Intranasal delivery; Ketorolac tromethamine; Poloxamer 407