Abstract Background information: @entity1499 ( @entity1500 ), an anticancer drug of choice, has poor permeability across blood-brain barrier (BBB) making it unsuitable for @entity1313 application. Its brain availability and scope of application was improved by preparation of reversible conjugate with @entity376 by capitalizing the endogenous transport system of @entity376 at BBB. Methods: To enhance its delivery to brain, @entity1500 was reversibly conjugated with @entity9108 by an @entity6346 linkage. It was characterized by advanced spectroscopy techniques including IR, NMR and @entity15 . Furthermore, conjugate was assessed for stability, @entity137 and drug release ability. In vivo distribution studies were done by radioscintigraphy study using (99m)Tc radioisotope. Results: The structure of prodrug was confirmed by (1)H-NMR, @entity7352 -NMR and Mass. The m/e (mass to charge ratio) fragment was found at [M   +   H] 711.32 in Mass spectra. Stability and metabolic studies suggested that conjugate was stable at physiological pH (in Phosphate buffer pH 7.4 t1/2 is 70.25        2.17   h and in plasma t1/2 is 193.57        2.03   min) and circulated adequately to release @entity1500 slowly in brain. In vivo biodistribution study showed that prodrug significantly increased the level of @entity1500 in brain when compared with pharmacokinetic parameter of parent drug. Conclusion: The brain permeability of @entity1500 was enhanced significantly by this conjugate.

Development and characterization of @entity376 - XXXX conjugate for enhanced brain delivery.

@entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity1313 :: ('MESH:D001932', 'Disease') :: ['brain tumor'] @entity7352 :: ('CHEBI:36928', 'Chemical') :: ['(13)C'] @entity9108 :: ('CHEBI:29967', 'Chemical') :: ['l-Lysine'] @entity376 :: ('CHEBI:25094', 'Chemical') :: ['lysine'] @entity1500 :: ('CHEBI:44185', 'Chemical') :: ['MTX'] @entity6346 :: ('CHEBI:32988', 'Chemical') :: ['amide'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['Methotrexate'] @entity15 :: ('MESH:D009103', 'Disease') :: ['MS']
@entity1499 :: (MESH:D008727,Chemical) :: ['methotrexate']
