Modulation of release mechanisms of methylene blue (MB) monomers and dimers from silica-MB@shellac synthesized by antisolvent crystallization.

Release behaviors of drugs from drug deliveries are crucial for the enhancement of therapy efficiency, reduction of toxicity and patient compliance. Herein, antisolvent crystallization is employed to coat methlyene blue (MB)-loaded silica by shellac precipitation (silica-MB@shellac), which is simultaneously induced by outward diffusion of H ions from particular silica-MB. The encapsulation of shellac shell on silica-MB modulates the aggregation state of MB, which endows silica-MB@shellac a decreased MB's thermal stability, enhanced photoluminescence intensity, improved stability against in vitro reduction by ascorbic acid and retained photodynamic therapy activity. From the absorbance of MB supernatant obtained during incubation, the concentrations of MB monomers and dimers are determined via a non-linear regression analysis to investigate the influence of shellac coating on MB's release mechanisms from silica-MB@shellac. According to the simulated models, small diffusion constants of MB are caused by limited diffusion through shellac shells with high compaction degrees. These are observed for samples synthesized under high supersaturation degree during antisolvent crystallization. High degree of supersaturation is achieved through increasing shellac concentration, additive amount and dropping rate of antisolvent, as well as decreasing pH values of aqueous buffers as antisolvent. Furthermore, a combined mechanism of Fickian diffusion and Case-IΙ relaxation is proposed to describe the release behaviors of MB monomer and dimers from silica-MB@shellac. Therefore, this work may shed light on the encapsulation method of polymer on drug-loaded powders and the control of aggregation states of photosensitizers to promote the photoluminescence intensity, photodynamic therapy efficiency and controlled release behaviors.