A MOF-based carrier for in situ dopamine delivery

Abstract

MIL-88A (Fe) MOF crystals were nucleated and grown around a polymer core containing superparamagnetic nanoparticles to assemble a new class of biocompatible particles for magnetophoretic drug delivery of dopamine. The carrier enabled efficient targeted release, dopamine protection from oxidative damage, long-term delivery and improved drug delivery cost-efficiency. After loading, dopamine was stable within the carrier and did not undergo oxidation. Drug release monitoring via spectrofluorimetry revealed a shorter burst effect and higher release efficiency than silica based carriers. The in vitro cytotoxicity at different MOF concentrations and sizes was assessed using PC12 cells as the neuronal cell model. The drug was directly uptaken into the PC12 cells avoiding possible side effects due to oxidation occurring in the extracellular environment.

Fig. 1. SEM images of MIL-88A MOF at different generations on PMP particles. (a) 1^st, (b) 2^nd, (c) 3^rd and (d) 4^th generation. (e) Crystal agglomerate diameter (μm) as a function of the generations. Results are the mean ± SD of ten measurements of PMP@ MIL-88A MOF agglomerate.

Fig. 2. SEM images of MIL-88A crystals at different generation on PMP particles. (a) 1^st (b) 2^nd (c) 3^rd and (d) 4^th. (e) Crystals size (μm) as a function of the growths. Results are the mean ± SD of ten measurements of crystal size.

Fig. 3. EDX mapping analysis of elements C (green), O (violet) and Fe (blue) in PMP@MIL-88A (Fe) MOF 2^nd generation.

Fig. 4. Image of DA-PMP@MIL-88A (black powder), (a) 1^st and (b) 2^nd generations, after several washing cycles with PBS. The particles are sensitive to the magnetic field and can be collected by a magnet.

Fig. 5. TGA analysis of PMP particles (red), MIL-88A MOF (black) and PMP@MIL-88A (Fe) (blue) in air at a heating rate of 10 °C min⁻¹.

Fig. 6. (a) Calibration curve of the dopamine, emission intensity λ_em: 327 nm vs. concentration in PBS solution. (b) Scheme of dopamine oxidation. (c) Fluorescence spectrum of dopamine in PBS as function of time. (d) Fluorescence spectra of PMP@MIL-88A (blue line) and dopamine release from PMP@MIL-88A (orange line) in PBS solution as function of time. λ_exc: 305 nm and λ_em: 327 nm. (e) DA (λ_exc: 305 nm) and (f) DQ (λ_exc: 390 nm) before (black line) and after the 10 hours (red line) required for the release test in PBS solution.

Fig. 7. The effect of PMP@MIL-88A and DA-PMP@MIL-88A (10, 20, 40 μg mL⁻¹) at different generations (a) 1^st, (b) 2^nd, (c) 3^rd on viability of PC12 for 24 h evaluated by trypan blue assay. P-value < 0.05 vs. control group. Legend: S= 1^st generation, S1 = 2^nd generation, S2 = 3^rd generation, suffix-DA = loaded with dopamine.

Fig. 8. (a) Effect of DA (0.664 μg mL⁻¹), PMP@MIL-88A and DA-PMP@MIL-88A (DA loading solution: 40 μg mL⁻¹) on a extracellular levels of dopamine in PC12 cells after 2, 4, 6, and 24 hours exposure, and (b) intracellular levels of dopamine in PC12 cells after 24 hours exposure.