Abstract
Chitosan and alginate hydrogels are attractive because they are highly biocompatible and suitable for developing nanomedicine microcapsules. Here we fabricated a polydimethylsiloxane-based droplet microfluidic reactor to synthesize nanomedicine hydrogel microcapsules using Au@CoFeB–Rg3 as a nanomedicine model and a mixture of sodium alginate and PEG-g-chitosan crosslinked by genipin as a hydrogel model. The release kinetics of nanomedicines from the hydrogel were evaluated by simulating the pH and temperature of the digestive tract during drug transport and those of the target pathological cell microenvironment. Their pH and temperature-dependent release kinetics were studied by measuring the mass loss of small pieces of thin films formed by the nanomedicine-encapsulating hydrogels in buffers of pH 1.2, 7.4, and 5.5, which replicate the pH of the stomach, gut and blood, and cancer microenvironment, respectively, at 20 °C and 37 °C, corresponding to the storage temperature of hydrogels before use and normal body temperature. Interestingly, nanomedicine-encapsulating hydrogels can undergo rapid decomposition at pH 5.5 and are relatively stable at pH 7.4 at 37 °C, which are desirable qualities for drug delivery, controlled release, and residue elimination after achieving target effects. These results indicate that the designed nanomedicine hydrogel microcapsule system is suitable for oral administration.
Highlights
Hydrogels are hydrophilic three-dimensional polymer networks, which can absorb and retain a large amount of water and swell without dissolving or losing their structural features.[1,2] Hydrogels have high water permeability, they are suitable for drug delivery systems, and the embedded proteins or drugs can be released through their porous microstructures.[3,4,5,6,7] Nanocomposite hydrogels are composed of polymer networks embedded with functional nanoparticles (NPs) or nanostructures.[8]
These types of poly(dimethylsiloxane) (PDMS) devices are fabricated using traditional so lithography based on SU-8 molds.[68,69]
A type of nanomedicine-encapsulating hydrogel for preparing nanodrug microcapsules was designed using Au@CoFeB–Rg3 as a type of nanomedicine model and a mixture of sodium alginate and polyethylene glycol (PEG)-g-chitosan crosslinked by genipin as a type of hydrogel model that combines the advantages of both chitosan and alginate
Summary
Several limitations reduce the efficacy of anticancer drugs directly administered to tumor tissues, such as short circulation time and transient high concentration due to uncontrolled drug release, unstable drug molecules and poor dispersion in the focal region, and lack of targeting.[22,23] In 2016, Chan et al analyzed the delivery efficiency of nanomedicines (NMs) to tumor sites in the last decade and found that the delivery efficiency of NMs is low, at an average of 0.7% for solid tumors, with a low penetration depth.[24,25] To achieve efficient drug delivery and high therapeutic efficiency of anticancer nanodrugs, nanodrug delivery systems of large speci c surface area, appropriate pore size, and high drug-loading capacity for controlled release at the desired cell microenvironment are desirable for enhanced penetration and retention in the focal region.[26,27,28,29,30,31,32,33,34,35,36] Shi et al.[37] reported a nanocomposite hydrogel doped with the porous and hollow-like structure of MgSiO3 NPs, which can be loaded with the anticancer drug doxorubicin. The natural polymer sodium alginate or chitosan hydrogels have received great interest owing to their biocompatibility, low toxicity, and degradability.[42,43,44,45] These types of hydrogels undergo pH-sensitive swelling and allow diffusion of drugs through their intrinsic micropores.[46] sodium alginate has poor mechanical properties and excessively high water solubility, so it must be chemically crosslinked to improve its stability in aqueous media.[47] Chitosan can attract negatively charged proteins via electrostatic interactions, which results in poor drug release.[48,49,50] But the low polymer concentration of the sol results in a hydrogel with poor mechanical strength. Genipin is used in traditional Chinese medicine for certain diseases and can spontaneously react with amino acids.[57,58] So genipin can be used to crosslink sodium alginate and modi ed chitosan to prepare oral drug capsules with pH- and temperature-sensitive characteristics for controlled release
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