Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement

• Published in: Langmuir Vol. 33; no. 45; pp. 12960 - 12972
• Main Authors: Tsao, Nadia H, Hall, Elizabeth A. H
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14-11-2017
• Subjects: Capsules - chemistry; Drug Delivery Systems; Drug Liberation; Silicon Dioxide; Solubility
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/acs.langmuir.7b02954

Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded delivery vehicle. The uptake and delivery were studied and compared with similar microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively charged lucigenin was encapsulated through an electrostatic mechanism, following a Type I Langmuir isotherm as expected, but with an additional multilayer uptake that leads to a much higher loading for the SiPCL system (∼280 μg/2.4 × 109 microcapsules compared with ∼135 μg/2.4 × 109 microcapsules for S/M/S). Whereas the lucigenin release from the S/M/S bubbles and capsules loaded below the solubility limit is consistent with diffusion from a monolithic structure, the SiPCL structures show distinct release patterns; the Weibull function predicts a general trend for diffusion from normal Euclidean space at short times tending toward diffusion out of fractal spaces with increasing time. As a slow release system, the dissolution time (T d) increases from 1 to 2 days for the S/M/S and for the low concentration, loaded SiPCl vehicles to ∼10 days for the high loaded microcapsules. However, T d can be reduced on insonation to 2 days, indicating the potential to gain control over the local enhanced release with ultrasound. This was tested for a docetaxel model and its effect on C4-2B prostate cancer cells, showing improved cell toxicity for concentrations below the normal EC50 in solution.