Protocol of Whey Protein Isolate-Based Microgel Targeted Delivery in Mouse Kidney
Oksana A Mayorova1, Mariia S Saveleva1, Daria A Terentyeva2
1Science Medical Center, Saratov State University, Saratov, Russia.
Abstract:
Every year, there is an increase in the number of cases of chronic kidney disease, and a delay in the initiation of adequate treatment can lead to kidney failure, which requires regular dialysis or transplantation. Intensive systemic therapy used to treat kidney diseases often has a negative impact on other weakened organs, making it crucial to ensure targeted delivery of medications directly to the kidneys and to minimize systemic side effects. In order to reduce the toxicity of medications and decrease dosages, innovative delivery methods are being developed, such as micro-sized targeted delivery systems, which ensure highly effective distribution of encapsulated drugs directly within the organs. In a recent article, we presented innovative emulsified microgels stabilized with whey protein isolate (WPI), specifically designed for targeted drug delivery to the kidneys. Our stability studies revealed that these microgels start to degrade after 72 h, with this degradation exhibiting a time-dependent profile. Furthermore, intravenous administration of the microgel suspension through the tail vein showed significant selective accumulation in both the liver and kidneys over a duration of 5 days. As part of our research, we present the protocol for synthesizing emulsion microgels derived from whey protein isolate. This article provides a comprehensive overview of the procedures for precursor preparation, along with an in-depth investigation of the emulsion system's stability over time. The protocol also includes the injection of an emulsion microgel suspension into the tail vein of mice, enabling the evaluation of their biocompatibility and potential therapeutic efficacy. This protocol outlines the precautions and important nuances that should be considered at each stage of the experiment. Key features • This protocol provides detailed instructions on the synthesis of fluorescently labeled emulsion microgels using mucoadhesive whey protein isolate, allowing the replication of this process. • The protocol describes in detail how to prepare samples for confocal microscopy. • We are exploring a method to study the stability of emulsion microgels by analyzing the size of emulsion droplets using optical microscopy. • We provide guidance on the administration of suspension into the tail vein of mice, followed by visualization of the microgels' body biodistribution.
Insights
Researchers developed novel whey protein isolate microgels for targeted kidney drug delivery, showing significant accumulation in kidneys and liver after intravenous injection in mice. This method aims to reduce systemic side effects and improve treatment efficacy for chronic kidney disease.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Pharmacology
Background:
- Chronic kidney disease (CKD) cases are rising, with delayed treatment leading to kidney failure.
- Current systemic therapies for kidney disease can harm other organs.
- Targeted drug delivery to kidneys is crucial to minimize side effects and improve efficacy.
Purpose of the Study:
- To present a protocol for synthesizing emulsion microgels stabilized with whey protein isolate (WPI) for targeted kidney drug delivery.
- To evaluate the stability and biodistribution of these novel microgels.
- To assess the biocompatibility and potential therapeutic efficacy of the microgel system.
Main Methods:
- Synthesis of fluorescently labeled emulsion microgels using mucoadhesive WPI.
- Stability studies of microgels using optical microscopy to analyze droplet size over time.
- Intravenous administration of microgel suspension into mice via tail vein.
- Confocal microscopy for sample preparation and visualization of microgel biodistribution.
Main Results:
- Emulsion microgels demonstrated time-dependent degradation, starting after 72 hours.
- Significant selective accumulation of microgels was observed in the liver and kidneys within 5 days post-injection.
- The protocol allows for the replication of microgel synthesis and evaluation of their in vivo behavior.
Conclusions:
- Whey protein isolate-based emulsion microgels are a promising system for targeted drug delivery to the kidneys.
- The developed protocol enables the synthesis and evaluation of these microgels for potential therapeutic applications in CKD.
- This approach offers a strategy to reduce drug toxicity and improve treatment outcomes for kidney diseases.


