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Abstract
Synthesis And Evaluation Of Pharmacological Activities Of Cyclodextrin Conjugates Of Methotrexate
Author(s): D Gupta, Deepali V Mhaske, S. S Kadam, S. R Dhaneshwar
In the present investigation methotrexate prodrugs of α-and γ-cyclodextrins were synthesized. The primary hydroxy group of α- and γ-cyclodextrins were used to block the acid group. The synthesis involved a series of protection and deprotection reaction. The esters were evaluated for stability in simulated gastric and intestinal fluid. The hydrolysis of cyclodextrin conjugates in colon is confirmed by the hydrolysis kinetics studies in rat fecal material. The esters were also evaluated for ulcerogenicity. Results of these studies established the primary aim of masking the ulcerogenic potential of free drug, by using 12-fold dose of the normal dose of methotrexate and equivalent doses of the esters.
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