Current Drifts in Design and Development of Prodrugs

Abstract

The design and development of prodrug is based on the objectivity to improve the pharmacokinetic and pharmacodynamic profiles including toxicity of the potent chemical entity. Currently, the prodrug approach is extended with conjugating the parent drug with a self immolating molecule or linker which itself assembles into nanoparticles and prolonged the blood circulation and having passive targeting ability. It also includes delivery of the drug at target site having specific pH condition, delivery of drug to brain by endogenous carrier molecule, NQO1 activable prodrug, prodrug with sustained release behavior, receptor targeted, dual action prodrug, activation via specific enzyme like human carboxylesterase, and phospholipase A2. Some other approaches to prodrug development are that the conversion of active pharmaceutical ingredient (API) into ionic liquids (ILs). In this the biocompatible ionic liquids include choline and amino acid esters are used. One of the anticancer drug methotrexate is formulated into ionic liquid form and used as potential anticancer prodrug. In addition to improvement in combination chemotherapy, there is photoresponsive hybrid prodrug that consists of a photoremovable protecting group. The release of doxorubicin and combrestatin A4 is mainly triggered by 405 nm light and 365 nm light respectively and displayed a quasi-sequential release behavior.