In Vitro Evaluation and Finite Element Simulation of Drug Release from Polydiacetylene-Polyethylene Glycol Stearate Nanovesicles
Abstract:Vesicles comprised of 10,12-pentacosadiynoic acid (PCDA) were modified, using polyethylene glycol 40 stearate (PEG40S), and crosslinked by ultraviolet (UV) irradiation to create polymerized nanovesicles for sustained drug release. Paclitaxel, a water-insoluble compound widely used in cancer chemotherapy, was used as a model drug to examine the physicochemical stability and release profiles of PCDA/PEG40S nanovesicles. TEM analysis revealed the formation of paclitaxel-encapsulated PCDA/PEG40S nanovesicles of 40 to 200 nm in size. Upon the addition of ethanol, instantaneous releases of paclitaxel in the amount of 28 μg/mL from polymerized PCDA/PEG40S nanovesicles and 108 μg/ml from unpolymerized ones were observed. This suggested the noncomplete drug release from polymerized PCDA/PEG40S nanovesicles due to their enhanced physicochemical stability by ultraviolet irradiation-induced polymerization, if compared to unpolymerized ones. An in vitro study demonstrated that an accumulative release of 24.1 ± 3.1% and 8.1 ± 1.7% of paclitaxel was obtained within 24 hrs from nanovesicles comprised of PCDA/PEG40S at a 9:1 and 7:3 molar ratio, respectively. A finite element model that considered the diffusion-driven releases and the reversible drug-vesicle interaction captured the sustained release of paclitaxel from polymerized PCDA/PEG40S nanovesicles. PCDA/PEG40S nanovesicles capable of sustained release and with enhanced physicochemical stability thus possess great potential for applications in drug release.
Document Type: Research Article
Publication date: January 1, 2012
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