Cyclodextrins as phototoxicity inhibitors in drug formulations: studies on model systems involving naproxen and β-cyclodextrin

• Published in: Journal of photochemistry and photobiology. A, Chemistry. Vol. 140; no. 1; pp. 67 - 74
• Main Authors: Partyka, Morgan, Au, Bao Ha, Evans, Christopher H
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 13-04-2001; Elsevier Science
• Subjects: Biological and medical sciences; Cyclodextrins; Drug formulations; General pharmacology; Medical sciences; Naproxen; Pharmacology. Drug treatments; Phototoxicity; Physicochemical properties. Structure-activity relationships; Phototoxicity; Cyclodextrins; Drug formulations; Naproxen; Stern Volmer diagram; Equilibrium constant; Oligoholoside; Association constant; Fluorescence spectrometry; Non steroidal antiinflammatory agent; Cyclodextrin; Binding capacity; Structure activity relation; Molecular association; Photosensitization; Arylpropionic acid derivatives; Physicochemical properties
• ISSN: 1010-6030; 1873-2666
• DOI: 10.1016/S1010-6030(01)00386-0

The binding of the phototoxic non-steroidal anti-inflammatory drug naproxen (NX) to β-cyclodextrin (β-CD) in the presence of alcohols or protein (bovine serum albumin, BSA) is described. Changes in the NX fluorescence spectrum shows that it forms a moderately strong 1:1 complex with β-CD in pH 7.4 aqueous buffer at room temperature (
K
app=475±35
M
−1). The presence of 1% linear alcohols (ethanol to pentanol) systematically lowers
K
app for the β-CD:NX complex. The greatest reduction is observed for the longest alkyl chain. Detailed analysis of
K
app as a function of [pentanol] suggests that three-member complexes involving the CD, NX and pentanol form (
K
3=141±32
M
−1). Quenching the fluorescence of NX with NaI shows that the β-CD cavity protects NX from this aqueous phase quencher. Addition of pentanol inhibits this protective effect. Ultra-violet irradiation of NX at pH 7.4 leads to formation of photoproducts. An amount of 10
mM β-CD strongly inhibits NX photoconversion. Addition of 1% pentanol essentially eliminates the photosuppressive effect of β-CD. By contrast to the moderate CD/NX binding, NX binds very strongly to BSA (
K
app=(3.2±1.6)×10
5
M
−1). Changes in the shape and energy of the NX fluorescence spectrum in the presence of BSA and separation experiments based on molecular weight support the view that BSA essentially displaces NX entirely from the CD environment. The implications of these results for application of CDs as in vivo phototoxicity inhibitors are discussed.