Lung cancer is a complicated long-term disease, which is extremely difficult to cure. A traditional single drug delivery system cannot achieve desired long-term controlled release of therapeutic compounds. Our previous studies have found that temperature-responsive micelles demonstrated high loading efficiency and a long-term controlled release rate, which allows them to be an efficient drug delivery system. We utilized temperature-responsive micelles and hyaluronic acid biopolymers to create a sandwich-like membrane based on hydrogen bonding by layer-by-layer (LBL) self-assembly technology. The multilayer films efficiently absorbed osimertinibthe third-generation inhibitor for nonsmall cell lung cancer (NSCLC) treatment. The release profile of osimertinib from the films is controlled by environmental stimuli. Block copolymer micelles with a poly(N-isopropylacrylamide) (PNIPAM) core were deposited into the multilayer films to introduce temperature sensitivity to the composite thin films. By the above approach, we built a drug carrier for the delivery of an anticancer drug, which potentially demonstrates good loading capacity, high morphology stability, and a controllable drug release mode. We investigated the films’ responsive behavior to temperature and ionic strength and loading capacity of the composite membrane and explored the influence of each component on the response of the drug release profile to environmental triggers. The films retained their morphology integrity after several temperature-triggered swelling/deswelling cycles based on atomic force microscopy and ellipsometry measurements. The mechanism of the intermolecular interaction and molecular motions in the system was studied to elucidate the relationship between structure and delivering efficiency of the system. Development of the LBL films can provide ideas for the modification of traditional drug delivery materials. More importantly, nanoparticle layer-by-layer self-assembly and micro/nanoscale structure manipulation for controlled release of therapeutic compounds are also beneficial to future design and development of innovative functional materials.
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 welldefined 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.
Using surface-initiated atom-transfer radical polymerization, temperature-responsive block polymers were functionalized on the surface of silica nanocapsules (SNCs) by a “grafting-from” technique. Favipiravir, a potential medicine candidate for the treatment of coronavirus disease (COVID-19), was encapsulated in polymer-coated SNCs and further incorporated into well-defined films by layer-by-layer self-assembly. The multilayer films composed of polymer-coated SNCs and poly(methacrylic acid) (PMAA) homopolymers exhibited swelling/deswelling behaviors under the trigger of a temperature stimulus. For the first time, the impact of steric hindrance on the assembling behavior, swelling/deswelling transition, and delivering capacity of nanocapsule-based multilayer films was investigated. SNCs with coronae of higher steric hindrance resulted in a larger layering distance during film growth. Moreover, the difference in the sustained release rates of the drug indicated their diverse diffusion coefficients and intermolecular interactions within the multilayer films, due to the presence of a methyl spacer at the amino group of nanocapsule coronae and weaker ionic pairing between SNC coronae and PMAA homopolymers. The profile of drug release from the films was dependent on the temperature value of the surrounding environment. At 37 and 40 °C, the films were able to efficiently entrap favipiravir, with as low as 50% released in 80 days, whereas a faster favipiravir release was triggered by exposure to a lower temperature value at 25 °C. This work demonstrates the first proof-of-concept platform of temperature-responsive SNC-incorporated multilayered films with a well-defined internal structure and a sustained release profile for on-demand in vitro drug delivery.
Using surface-initiated atom transfer radical polymerization (ATRP), block polymers with a series of quaternization degrees were coated on the surface of silica nanocapsules (SNCs) by the “grafting-from” technique. Molnupiravir, an antiviral medicine urgently approved for the treatment of SARS-CoV-2, was encapsulated in polymer-coated SNCs and further incorporated into well-defined films with polystyrene sulfonate (PSS) homopolymers by layer-by-layer (LBL) self-assembly via electrostatic interactions. We investigated the impact of the quaternization degree of the polymers and steric hindrance of functional groups on the growth mode, swelling/deswelling transition, and drug-delivering efficiency of the obtained LBL films. The SNCs were derived from coronas of parent block polymers of matched molecular weights—poly( N -isopropylacrylamide)- block -poly( N , N -dimethylaminoethyl methacrylate) (PNIPAM- b -PDMAEMA)—by quaternization with methyl sulfate. As revealed by the data results, SNCs with coronas with higher quaternization degrees resulted in a larger layering distance of the film structure because of weaker ionic pairing (due to the presence of a bulky methyl spacer) between SNCs and PSS. Interestingly, when comparing the drug release profile of the encapsulated drugs from SNC-based films, the release rate was slower in the case of capsule coronas with higher quaternization degrees because of the larger diffusion distance of the encapsulated drugs and stronger hydrophobic–hydrophobic interactions between SNCs and drug molecules.
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