Synthesis of <scp>CO₂</scp>‐Based Polyurethane Hydrogels for the Loading and In Vitro Release of 5‐Fluorouracil Acetic Acid Prodrug

ABSTRACT Vinyl functional polycarbonate‐co‐polyester (including poly(4‐vinyl‐1,2‐cyclohexene carbonate) [PVCHC, P 1 ], poly(propylene carbonate‐co‐4‐vinyl‐1,2‐cyclohexene carbonate) [PPC‐co‐PVCHC, P 2 ], poly(propylene carbonate‐co‐4‐vinyl‐1,2‐cyclohexene carbonate‐co‐lactide) [PPC‐co‐PVCHC‐co‐PLA, P 3 ], poly(4‐vinyl‐1,2‐cyclohexene carbonate‐co‐lactide) [PVCHC‐co‐PLA, P 4 ]) are used to prepare polyurethane gels by the reaction with hexamethylene diisocyanate (HDI), in the coexistence of hydroxypropyl methyl cellulose (HPMC) and polyethylene glycol (PEG). The vinyl groups of thus‐prepared polyurethane gels were partly derivatized to amino groups, resulting in amino‐modified gels PU i ‐NH 2 s ( i = 1, 2, 3, 4, produced from P 1 , P 2 , P 3 , P 4 , respectively), which display a high swelling ratio in water (vary from 824.6% to 1261.4%), and can load 5‐fluorouracil acetic acid physically (drug loading efficiency varies from 148.5 to 189.6 mg/g). The physically loaded gels display a slow and controlled release rate of 5‐FUA in in vitro release experiments (drug release period varies from 16 to 44 h, implying different compounding ability of different hydrogels). 5‐Fluorouracil acetic acid can also react with PU i ‐NH 2 s gels by an amidation reaction to form gels chemically loaded by drugs (the grafting efficiency varies from 40.91% to 57.86%), and the drug fragments can be detected by UV absorbance after different hydrodegradation periods in 2 M NaOH methanol solution at 50°C (varies from 20 to 96 h), reflecting different water‐resistance performance of different gels.