Abstract
In this study, the toxicity of 4-hydroxytamoxifen (4-OHT) on human Schwann cells (HSCs) was evaluated. Substantial alterations in the cell morphology and viability were observed at 4-OHT concentrations higher than 3 µg/mL. Therefore, we designed and synthesized a drug–polymer conjugate, based on N-(2-hydroxypropyl)methacrylamide (HPMA) and ethyl acrylate (EA) for delivering 4-OHT to the target tissue without the detrimental consequences of the systemic therapy currently used. The macromer carrier of 4-OHT (MATX), with a functionalization degree of 80%, was synthesized in two steps and verified by 1H-NMR and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectroscopy. MATX was conjugated to the poly(HPMA-co-EA) copolymer network via radical polymerization. The influence of MATX on the physical, chemical, and mechanical properties of poly(HPMA-co-EA-co-MATX) with a ratio of 69/29/2 wt% was compared to those of poly(HPMA-co-EA) networks with a similar feed mixture. The in vitro release of 4-OHT within 1 month was 6 wt% of the total amount of drug linked to the copolymer backbone.
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