HPMA copolymer-dexamethasone prodrug

HPMA copolymer-dexamethasone prodrug (P-Dex) is a macromolecular, pH-sensitive polymeric prodrug of the potent glucocorticoid dexamethasone, developed by the University of Nebraska Medical Center. The prodrug consists of dexamethasone covalently conjugated to an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone via an acid-cleavable hydrazone linker. This design exploits the 'extravasation through leaky vasculature and inflammatory cell-mediated sequestration' (ELVIS) mechanism to passively target sites of active inflammation, such as inflamed joints in rheumatoid arthritis, the kidneys in lupus nephritis, and injured brain tissue in traumatic brain injury (TBI). Upon cellular internalization by inflammatory cells (such as macrophages) or exposure to the acidic microenvironment of inflamed tissues, the hydrazone bond is cleaved, releasing active dexamethasone locally. This targeted delivery significantly enhances therapeutic efficacy while mitigating systemic glucocorticoid-associated toxicities, such as osteoporosis, bone loss, and adrenal gland atrophy.

Other names

HPMA copolymer-dexamethasone conjugateN-(2-hydroxypropyl)methacrylamide copolymer-dexamethasone conjugateN-(2-hydroxypropyl)methacrylamide copolymer-dexamethasone prodrugP-DEXProGel-Dexmacromolecular dexamethasone prodrug