Hydroxypropyl Cyclodextrin Particles: Excellent Carriers for Controlled Release of Toxic and Labile Drugs With High Blood Compatibility and No Cytotoxicity

ABSTRACT Using 2‐Hydroxypropyl beta‐cyclodextrin (2‐HP‐β‐CD), p(HP‐β‐CD) particles were prepared using divinyl sulfone (DVS) as crosslinker in microemulsion system with smooth surfaces with tens of micrometers size range. P(HP‐β‐CD) particles are negatively charged even at low pHs, for example, ζ = −2.5 mV at pH 2 and decreased with increase in solution pHs, for example, ζ = ~ −12.5 mV at pH 12. The prepared p(HP‐β‐CD) particles afforded a loading capacity of 89.5 ± 1.6 μg/mg of vancomycin, a relatively hydrophilic model drug, corresponding to a loading amount of 8.9% ± 0.2% and an encapsulation efficiency of 17.9% ± 0.4%. Also, 69.1 ± 2.4 μg/mg of vancomycin was released in 24 h, corresponds to 76.8% ± 1.9% of the loaded vancomycin amount. Vancomycin release from p(HP‐β‐CD) particles was best described by the first order kinetic model, which showed a high correlation coefficient ( R 2 = 0.9904) and low sum of squares due to regression (SSR = 10.44) and Chi square ( χ 2 = 0.36) values, indicating a concentration‐dependent mechanisms. Moreover, blood compatibility testing also demonstrated excellent compatibility, with a hemolysis index% (HI%) of 0.8% ± 0.06% and blood clotting index% (BCI%) of 87 ± 3, even at a concentration of 1000 μg/mL. Furthermore, cytotoxicity testing with L929 fibroblast cell further confirmed that the particles were non‐toxic and mitigated drug toxicity at high concentrations yielding approximately 80% ± 2% cell viability after 25 h of incubation.