Abstract
Cilostazol (CLZ) acts as a vasodilator and antiplatelet agent and is the main drug for the treatment of intermittent claudication (IC) related to peripheral arterial disease (PAD). The usual oral dose is 100 mg twice a day, which represents a disadvantage in treatment compliance. CLZ presents several side effects, such as headache, runny nose, and dizziness. This paper aimed to obtain novel polymeric nanocapsules prepared from poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) blend containing CLZ. Nanocapsules showed pH values between 6.1 and 6.3, average size lower than 137 nm, low polydispersity index (<0.22) and negative zeta potential. These nanoformulations demonstrated spherical shape with smooth surface. Results achieved by X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated drug amorphization compared to pure CLZ. Fourier-transformed infrared spectroscopy (FTIR) showed no chemical bonds between drug and polymers. Formulations presented suitable stability for physical parameters. The in vitro drug release demonstrated prolonged release with no burst effect. Drug release was controlled by both mechanisms of polymer relaxation/degradation and Fickian diffusion. Moreover, chosen CLZ-loaded nanocapsules provided an in vivo prolonged antiplatelet effect for CLZ statistically similar to aspirin. These formulations can be further used as a feasible oral drug delivery carrier for controlled release of CLZ in order to treat PAD and IC events.
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