Development of Injectable Silk Hydrogel for Nanoprodrugs Control Release

In traditional drug delivery systems, nanoparticles tend to accumulate at tumor sites due to the enhanced permeability and retention (EPR) effect, resulting in therapeutic efficacy. However, in the process of transporting through the blood, there is inevitable diffusion of drug to the normal tissue, causing side effects and reducing efficacy at the tumor site. An approach for such problems is to selectively release the drug at the tumor site through localized drug administration.<br/>Silk protein hydrogels are inherently suitable for biological applications due to their permeability, high water content, and structural properties compatible with cell membranes. Its biodegradability can also be modified and subsequently utilized to control the drug release behavior, making silk hydrogel a potential drug-loading material.&lt;span style="font-size:10.8333px"&gt; &lt;/span&gt;In vivo, hydrogels can be broken down by proteases. By changing the properties of the hydrogel, the degradation rate of the silk hydrogel can be tuned, therefore achieving controllability over the drug release. The study of injectable silk protein hydrogels as drug delivery systems has achieved good results in research for breast and liver cancers, but the research focus of controlling water-insoluble drug loading and drug release properties of hydrogels has not yet been realized. The aim of this study is to fabricate silk protein hydrogels that could be used as nano-prodrug carriers.<br/>To this end, systematic changes in silk hydrogel preparation conditions were screened, and the obtained hydrogels were then used to load and release various types of drugs. Changes in dissolution conditions and gel parameters such as temperature, sonication time, shaking, stirring time, etc., during the preparation of hydrogels are considered to be factors that affect the performance of hydrogels. The properties of silk protein hydrogels were analyzed by gel fraction, swelling ratio, degradation rate, FT-IR, XRD, rheometer and so on.<br/>In this report, calcium chloride solution was used to dissolve fibroin to obtain hydrogels with gelation times ranging from 1 to 4 days. By changing the gelation conditions, hydrogels with different properties were obtained. In addition, the loading of nano-prodrugs (NPDs) has been preliminary investigated. The in vitro drug release behavior of drug-loaded hydrogels will be studied. We expect to create an injectable hydrogel in which degradability can be controlled in vivo. This means that drug release can be manually controlled.