Host-guest complexation of oxicam NSAIDs with beta-cyclodextrin.
Spectroscopic and molecular modeling techniques have been employed to study the interaction of the oxicam group of nonsteroidal antiinflammatory drugs (NSAIDs) with a polysaccharide such as beta-cyclodextrin (beta-cd). beta-cd is a good drug delivery system and is known to reduce harmful side effects of these drugs in the gastrointestinal tract and to increase their clinical efficacy. A detailed understanding of such host-guest interaction helps in designing a better drug delivery system coupled with increased therapeutic potential. However, there exists a controversy as to which prototropic form of piroxicam, a drug belonging to the oxicam group, becomes encapsulated in the host and also the stoichiometry of binding. In this study, we have revisited that controversy using steady state fluorescence, absorption, fluorescence anisotropy measurements, and molecular modeling techniques. In addition, we have for the first time studied the interactions of two other oxicam drugs, viz. tenoxicam and meloxicam, with beta-cd in aqueous solution. In all cases the neutral forms of these drugs were incorporated in the beta-cd cavity with a binding stoichiometry of 1:1 host : guest. The values of the binding constants for piroxicam, meloxicam, and tenoxicam with beta-cyclodextrin are 134 +/- 21, 114 +/- 15, and 115 +/- 13 M(-1), respectively. Molecular modeling studies show that the minimum energy configuration gives favorable interaction energy between the host and the guest in the complex with 1:1 stoichiometry when the conjugated rings of the drugs are inside the hydrophobic bucket-like cavity of beta-cd and the third ring is exposed to the solvent.
Banerjee
Rona
R
Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Calcutta, 700 064, India.
Chakraborty
Hirak
H
Sarkar
Munna
M
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001665:Binding Sites; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D008958:Models, Molecular; D015394:Molecular Structure; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D046911:Macromolecular Substances; D047392:beta-Cyclodextrins; C031215:betadex