title: pH-and thermo-sensitive pluronic/poly(acrylic acid) in situ hydrogels for sustained release of an anticancer drug.
abstract: In this study, we developed oral in situ gelling formulations composed of pluronic (Plu) and polyacrylic acid (PAA) for the delivery of an anticancer drug, epirubicin (Epi). We investigated various Plu/PAA/Epi formulations for their physicochemical properties and in vitro permeation and accumulation, as well as for in vivo pharmacokinetic and antitumor efficacy. A scanning electron microscopic (SEM) image of Plu 14%/PAA 0.75%/Epi hydrogel showed a sponge-like structure. This formulation has suitable gelation time, water content, bioadhesive force, structural stability, and a high permeation percentage of Epi, with sustained drug release characteristics for 96 h. This hydrogel was retained at the end of the ileum near the colon of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after oral administration in this formulation, Epi had prolonged half-life, greater area under the curve, and higher relative bioavailability than in an oral Epi solution. In vivo tumor growth inhibition of Epi in this formulation was more pronounced compared with oral Epi and intravenous Epi solutions in CT-26 mouse colon adenocarcinoma bearing Balb/c mice. This study highlights the advantages of using oral in situ temperature- and pH-sensitive hydrogels for future cancer therapy.
authors.affiliation: Department of Biological Sciences and Technology, National University of Tainan, Tainan, Taiwan. yulilo@mail.nutn.edu.tw
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Lo
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Hsu
authors.forename: Hong-Ru
authors.initials: HR
authors.lastname: Lin
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D015251:Epirubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D020442:Poloxamer / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D020442:Poloxamer; D015251:Epirubicin; C006903:carbopol 940