TY - JOUR
T1 - A novel Mitomycin C-Triamcinolone conjugate for the prevention of proliferative vitreoretinopathy
T2 - In-vitro efficacy and rat retinal toxicity
AU - Macky, Tamer A.
AU - Soliman, Mahmoud M.
AU - Oelkers, Carsten
AU - Heredia, Martin L.
AU - Künzel, Eva
AU - Baerbel, Rohrer
AU - Crosson, Craig E.
AU - Rohr, Jürgen
PY - 2005
Y1 - 2005
N2 - A novel conjugate of Mitomycin C (MMC) and Triamcinolone Acetonide (TA) was synthesized and anlyzed in respect of its hydrolysis rate, retinal toxicity and antiproliferative properties, the latter in comparison with MMC, TA, and an unconjugated mixture of MMC and TA (1:1). The two drugs, TA and MMC, were connected, using glutaric acid as a linker molecule, to provide a conjugate that delivers equimolar concentrations of both agents. To determine the rate of hydrolysis, the conjugate was dissolved in 50% of 0.1M phosphate buffer (pH 7.4) and propylene glycol (PG). Over a period of 180 hours, samples were analyzed by HPLC to determine the rate of appearance of free MMC and TA. The antiproliferative activity of the MMC-TA conjugate was assessed using fibrolast cells (NIH 3T3 cell line) cultured in DMEM and 10% bovine serum, which were exposed for 48 hours to different concentrations of half-life of 23.6 hours in aqueous solutions. The IC50 for the MMC-TA conjugate and the MMC, were 2.4 and 1.7 μM, respectively. However individuals responses at concentrations above 3μM showed that the conjugate was less active than MMC alone. The TA alone showed only limited inhibition of cell growth, compared to controls, at a concentration of 3nM (P values <0.001). Electrophysiological and histopathological studies evaluating the intravitreal injected conjugate showed no evidence of toxicity to the neurosensory retina in rats. The data provide evidence that the MMC-TA conjugate could be used as a slow-release drug delivery system. This could in turn be used to modulate the wound healing process occurring in proliferative vitreoretinopathy.
AB - A novel conjugate of Mitomycin C (MMC) and Triamcinolone Acetonide (TA) was synthesized and anlyzed in respect of its hydrolysis rate, retinal toxicity and antiproliferative properties, the latter in comparison with MMC, TA, and an unconjugated mixture of MMC and TA (1:1). The two drugs, TA and MMC, were connected, using glutaric acid as a linker molecule, to provide a conjugate that delivers equimolar concentrations of both agents. To determine the rate of hydrolysis, the conjugate was dissolved in 50% of 0.1M phosphate buffer (pH 7.4) and propylene glycol (PG). Over a period of 180 hours, samples were analyzed by HPLC to determine the rate of appearance of free MMC and TA. The antiproliferative activity of the MMC-TA conjugate was assessed using fibrolast cells (NIH 3T3 cell line) cultured in DMEM and 10% bovine serum, which were exposed for 48 hours to different concentrations of half-life of 23.6 hours in aqueous solutions. The IC50 for the MMC-TA conjugate and the MMC, were 2.4 and 1.7 μM, respectively. However individuals responses at concentrations above 3μM showed that the conjugate was less active than MMC alone. The TA alone showed only limited inhibition of cell growth, compared to controls, at a concentration of 3nM (P values <0.001). Electrophysiological and histopathological studies evaluating the intravitreal injected conjugate showed no evidence of toxicity to the neurosensory retina in rats. The data provide evidence that the MMC-TA conjugate could be used as a slow-release drug delivery system. This could in turn be used to modulate the wound healing process occurring in proliferative vitreoretinopathy.
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M3 - Article
AN - SCOPUS:33746347728
SN - 1765-3169
VL - 1
SP - 18
EP - 27
JO - EVRS Educational Electronic Journal
JF - EVRS Educational Electronic Journal
IS - 5
ER -