title: Evaluation of thermosensitive poloxamer 407 gel systems for the sustained release of estradiol in a fish model.
abstract: The purpose of this study was to develop and evaluate a delivery system comprising a thermosensitive gel for the sustained release of steroidal hormones in fish, over an extended period of time after a single intramuscular (i.m.) injection and for the improved reproductive performance in fish. Controlled delivery systems based on thermosensitive gels are easy to prepare, low cost and high versatility dosage forms, which have been shown to be effective in several animal species for sustained release of hormones. In this work, a thermosensitive gel system based on poloxamer 407 in water:ethanol medium, able to work as a prolonged release carrier for 17β-estradiol (E2), has been developed. Such a system was able to solubilize the lipophilic E2 and to gel at the required water temperature for fish rearing (20°C). Moreover, the system exhibited the best injection condition at temperatures below 15°C when the system behaved as a low viscosity Newtonian liquid. The thermosensitive gel system was tested in vivo in the fish model, Carassius auratus, and the results compared with a single i.m. injection of E2 dissolved in corn-oil and other relevant control systems not containing E2. The results were particularly interesting, since fish injected with the E2 thermosensitive gel formulation, showed significantly higher levels of the circulating hormone than corn oil-E2 treated animals at 72 and 96h after injection. In addition, the thermogel system was able to sustain the plasma level of E2 for about 11days. The increased plasma levels of E2 were also accompanied by maintained higher values of plasma vitellogenin (VTG), thus suggesting that the thermosensitive polymer based delivery system could prevent rapid hepatic clearance of E2, resulting in prolonged stimulation of estrogen receptor-mediated pathways in goldfish.
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cespi
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bonacucina
authors.affiliation: University of Camerino, School of Biosciences and Veterinary Medicine, Camerino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pucciarelli
authors.affiliation: University of Camerino, Unità Ricerca e Didattica San Benedetto del Tronto (URDIS), San Benedetto del Tronto, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cocci
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: Diego Romano
authors.initials: DR
authors.lastname: Perinelli
authors.affiliation: University of Urbino, Department of Biomolecular Sciences, Urbino, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Casettari
authors.affiliation: IDentity, 19 Cavendish Crescent North, The Park, Nottingham NG7 1BA, UK.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Illum
authors.affiliation: University of Camerino, School of Pharmacy, Camerino, Italy.
authors.forename: Giovanni Filippo
authors.initials: GF
authors.lastname: Palmieri
authors.affiliation: University of Camerino, School of Biosciences and Veterinary Medicine, Camerino, Italy; University of Camerino, Unità Ricerca e Didattica San Benedetto del Tronto (URDIS), San Benedetto del Tronto, Italy. Electronic address: francesco.palermo@unicam.it.
authors.forename: Francesco Alessandro
authors.initials: FA
authors.lastname: Palermo
authors.affiliation: University of Camerino, School of Biosciences and Veterinary Medicine, Camerino, Italy.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Mosconi
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood* / Q000138:chemical synthesis; D005782:Gels / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D006054:Goldfish; D023421:Models, Animal; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D020442:Poloxamer; D004958:Estradiol
keywords: 17β-Estradiol; 17β-Estradiol (PubChem CID: 5757); Goldfish; Poloxamer; Poloxamer 407 (PubChem CID: 24751); Sustained release; Thermosensitive gel; Vitellogenin