title: Prednisolone-α-cyclodextrin-star poly(ethylene glycol) polypseudorotaxane with delayed pH-sensitivity as a targeted drug delivery system.
abstract: The acylation of prednisolone 20-hydrazone with star poly(ethylene glycol) tetracarboxylic acid (M = 20,000) has been used to prepare the corresponding pH-sensitive conjugate. With α-cyclodextrin, this conjugate forms a polypseudorotaxane, which was characterised by means of (1)H NMR spectra, powder X-ray diffraction patterns and STM microscopy. The rate of acid-catalysed hydrolysis of the conjugate was studied under in vitro conditions in model media of hydrochloric acid solutions, phosphate and acetate buffers (pH 2-5.8). The acid-catalysed hydrolysis (at pH 2) of the polypseudorotaxane was ca 3.5 times slower than that of the original conjugate. After 1h in this medium, 86% of the covalently attached prednisolone remained unchanged. The prepared polypseudorotaxane represents a promising peroral transport system of prednisolone with a pH-sensitive linker with delayed acid-catalysed hydrolysis thanks to protection at the molecular level using α-cyclodextrin.
authors.affiliation: Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
authors.forename: Eliška
authors.initials: E
authors.lastname: Bílková
authors.forename: Miloš
authors.initials: M
authors.lastname: Sedlák
authors.forename: Aleš
authors.initials: A
authors.lastname: Imramovský
authors.forename: Petra
authors.initials: P
authors.lastname: Chárová
authors.forename: Petr
authors.initials: P
authors.lastname: Knotek
authors.forename: Ludvík
authors.initials: L
authors.lastname: Beneš
mesh_terms: D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients; D005782:Gels; D005938:Glucocorticoids / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D043862:Rotaxanes / Q000737:chemistry*; D047391:alpha-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D005079:Excipients; D005782:Gels; D005938:Glucocorticoids; D006835:Hydrazones; D043862:Rotaxanes; D047391:alpha-Cyclodextrins; C569744:star poly(ethylene glycol)hydrazide-prednisolone-20-hydrazone; D011092:Polyethylene Glycols; D011239:Prednisolone; C032613:alpha-cyclodextrin