Electrostatically Assembled Multilayered Films of Biopolymer Enhanced Nanocapsules for on-Demand Drug Release

We describe layer-by-layer (LbL) buildup and pH-responsive behavior of multilayer films of alginate/chitosan/alginate -modified silica nanocapsules (SNCs) and chitosan (CS) biopolymers via electrostatic interaction. The SNC/CS films exhibit pH-triggered swelling/deswelling transitions under physiological conditions. Fulvestrant, an FDA-approved selective estrogen receptor down-regulator agent for the treatment of breast cancer, was encapsulated in SNCs and further incorporated into the LbL films. The drug release profile from the films was dependent on pH value of the surrounding environment. At pH 7.4, the films were able to efficiently entrap fulvestrant, with only ∼38% released in 120 days, whereas exposure to a lower pH value (pH 5.0) triggered faster fulvestrant release in phosphate buffer solution at 37 °C. Atomic force microscopy and ellipsometry showed that the films retained their structural integrity in PBS after several swelling/deswelling cycles. SNC/CS LbL films demonstrated repeated on/off drug release under external triggers, allowing consistent fulvestrant release (∼14-18% of encapsulated fulvestrant released for each cycle) over a 10-day period without significant change in drug release rate. This work demonstrates the first proof-of-concept platform of SNC-incorporated films with well-defined internal structure, good stability, high loading capacity, and controlled/sustained release profile for on-demand drug delivery. With great versatility to use various active compounds and building blocks, the films may have high potential for broad applications such as implantable biosensors and antifouling coatings.