Chemically Cross-Linked Poly(β-Cyclodextrin) Particles as Promising Drug Delivery Materials

One-pot synthesis of poly(beta-cyclodextrin) (p(beta-CD)) micro-/nanoparticles was accomplished using two different cross-linkers, divinyl sulfone (DVS) as p(beta-CD)-1 and trimethylolpropane glycidyl ether (TMPGDE) as p(beta-CD)-2. High gravimetric yields of 84 +/- 4 and 62 +/- 6%, respectively, were attained for p(beta-CD)-1 and p(beta-CD)-2 particles. The p(beta-CD)-1 and p(beta-CD)-2 particles had spherical shapes with 5.09 +/- 0.24 and 0.60 +/- 0.01 mu m diameters, respectively, and exhibited good water dispersibility at physiological pH, and their isoelectric points were calculated correspondingly to be pH 1.1 and 1.2. The surface areas of p(beta-CD)-1 and p(beta-CD)-2 particles were determined to be 4.76 +/- 0.6 and 2.18 +/- 0.2 m(2)/g, respectively. Moreover, p(beta-CD) particles were found to be biocompatible with more than 98% cell viability on human retinal pigment epithelial (ARPE-19) cells at 0.1 mg/mL concentration. Also, p(beta-CD)-1 particles exhibited 52.81 +/- 9.5% Fe(II) chelation capacity at 1.0 mg/mL concentration. The hemolysis and coagulation tests revealed that p(beta-CD)-1 particles possessed excellent blood compatibility with a 1.18 +/- 0.60% hemolysis ratio and a 92.02 +/- 1.02% clotting index even at 2.0 mg/mL concentration, whereas the safety limit of p(beta-CD)-2 particles for blood interactions was determined to be 0.5 mg/mL. The in vitro drug release performances of p(beta-CD)-1 and p(beta-CD)-2 particles for hydrophobic acyclovir and hydrophilic vancomycin model drugs at pH 7.4 PBS showed sustained releases of 2.14 +/- 0.34 and 1.34 +/- 0.43 mg/g acyclovir and 51.90 +/- 1.09 and 61.26 +/- 3.71 mg/g vancomycin within 24 h, respectively. Kinetic modeling of experimental release data revealed the best fit for drug release from p(beta-CD) particles mediated by the Korsmeyer-Peppas model.

Automated summary

The one-pot synthesis of poly(beta-cyclodextrin) (p(beta-CD)) micro/nanoparticles using different cross-linkers proved to have good physicochemical properties, including biocompatibility, blood compatibility, and sustained drug release capabilities.