Polydopamine particles as nontoxic, blood compatible, antioxidant and drug delivery materials

Abstract

Herein, the potential biomedical application of poly(3,4-dihyroxyphenyl)ethylamine, (poly(dopamine)-p(DA)) particles is reported. P(DA) particles with the size about 100 nm, 18.05 m²/g specific surface area, and mesoporous structure (7.19 nm pore width) were prepared and shown to be chemically modifiable using chlorosulfonic acid (CSA) and 3-CHloro-2 hydroxypropyl) trimethylammonium chloride solution (CHPACl) to obtain sulfonic acid and quaternary amine group containing modified p(DA) particles, m-p(DA)-CSA and m-p(DA)-CHPACl particles, respectively. The hydrolytic degradation of p(DA) particles at different pHs, including 1, 7.4 and 11, was carried out at 37.5 °C. These degradation studies revealed that p(DA) is slightly degradable at pH 1 and pH 7.4 with weight losses of 13.01 ± 0.08% and 7.26 ± 0.23% in 11 days, respectively. At pH 11, a sustained degradation that is almost linear degradation with time was observed for up to 30 days, with a total weight loss of 21.42 ± 0.88%. Furthermore, p(DA) particles were tested for cell toxicity against COS-1 cells and found non-toxic up to 50 μg/mL with 95.6 ± 4.5% cell viability as compared to 37.5 ± 0.03% for DA molecules. The p(DA) particles and DA were also compared for their ability to inhibit α-glucosidase; both inhibited α-glucosidase inhibition activity a concentration-dependent fashion: at concentrations of 500-4000 μg/mL, p(DA) provided 8.52-27.67% inhibition while DA inhibited 42.8-67.7% over the same concentration range. Furthermore, p(DA) particles were found to be blood compatible e.g., non-hemolytic with 1.87 ± 0.97% hemolysis ratio up to 50 μg/mL concentration and with 86.7% blood clotting index. Interestingly, p(DA) particle can be considered as an effective antioxidant with 33.5 ± 3.9 μg/ mL total phenol content in terms of gallic acid equivalency and 0.89 ± 0. 30 μmol/g trolox equivalent antioxidant capacity (TEAC). Finally, p(DA) particles and their modified forms, m-p(DA)-CSA, and m-p(DA)-CHPACl, were shown to be useful as active agent/drug delivery devices by using acyclovir as a model drug that can be readily loaded into particles and released at longer times at higher amounts for the modified p(DA) particles at physiological conditions.

Keywords: Drug delivery device; Modifiable phenolic microgel/nanogel; Poly(dopamine) particles; biocompatible/blood compatible antioxidant materials.