Zhejiang University to Transfer High-Permeability Polymeric Nanocapsule Technology for RMB 300,000

Recently, Zhejiang University released a public notice on the transformation of scientific and technological achievements, proposing to transfer related rights through agreed pricing.“A High-Penetration Polymer Nanocapsule and Its Preparation Method and Application”Assignment of relevant patents, with an assignment fee of300,000 yuan. The inventors of this patent areShao Shiqun and his team。

The present invention discloses a highly permeable polymeric nanocapsule, as well as its preparation method and applications. The nanocapsule exhibits oral stability and mucus-penetrating properties both in vitro and in vivo, enabling rapid cellular internalization. It mitigates radiation-induced injury by releasing antioxidants within the intestine, significantly reducing oxidative stress levels in intestinal tissues following radiotherapy, and alleviating the severity of intestinal inflammation and ulceration.

The treatment of diseases such as inflammatory bowel disease and radiation colitis has long faced core challenges, including inefficient drug delivery, poor targeting, and significant side effects. Traditional therapeutic agents are mostly administered systemically, making it difficult to achieve precise accumulation at the lesion site. This results in suboptimal therapeutic efficacy and a tendency to cause toxicity to normal tissues, leading to adverse reactions such as nausea and vomiting, which severely impair patients' quality of life.

FromDrug Delivery LevelExisting nanocarrier technologies suffer from several limitations. On one hand, the intestinal mucus layer forms a natural biological barrier; most nanoparticles are readily adsorbed by the mucus, making it difficult for them to penetrate and reach intestinal epithelial cells, thereby resulting in low drug bioavailability. On the other hand, these technologies lack intelligent responsive mechanisms, leading to nonspecific drug release in vivo. They cannot dynamically adjust the release rate based on the microenvironment of the lesion, which further reduces the specificity of the treatment.

Furthermore, macromolecular drugs (e.g., proteins and nucleic acids) are susceptible to degradation by gastric acid and digestive enzymes in the gastrointestinal tract, resulting in poor stability and compromised therapeutic efficacy. This issue is particularly pronounced in the context of oral administration.

For specific conditions such as radiation colitis, patients experience a significant increase in oxidative stress levels in intestinal tissues following radiotherapy, leading to frequent inflammation and ulceration. However, existing treatments struggle to precisely mitigate oxidative damage at the lesion sites, and there is a lack of delivery systems that combine mucus-penetrating capabilities with intestinal stability. This prevents drugs from effectively reaching and acting upon the damaged areas. These challenges have trapped clinical treatment in a dilemma of "insufficient efficacy" and "pronounced side effects," creating an urgent need for a novel drug delivery solution that offers high permeability, targeted responsiveness, and biological stability to overcome the core challenges of targeted therapy.

It is precisely what exists in the treatment of inflammatory bowel disease and radiation colitis“Low drug delivery efficiency, poor targeting, and insufficient stability of macromolecules”clinical pain points have prompted the research team to conduct targeted technological breakthroughs. The core advantage of the patented technology “High-Penetration Polymer Nanocapsules and Their Preparation Methods and Applications,” which is being commercialized in this instance, lies inDeveloping an integrated drug delivery solution based on “core-shell structure design + ROS-responsive intelligence”Achieving end-to-end technological innovation spanning carrier stability, biological barrier penetration, and targeted release.

This technology has pioneered a disruptive breakthrough in carrier structure design, innovativelyAdopts a "core-shell" core-shell structure, with the help ofInterfacial Polymerization ProcessDeveloping nanocarriers with both stability and high permeability.

The core is loaded with bioactive molecules such as catalase and superoxide dismutase, while the shell is formed by the polymerization of cationic monomers, tertiary amine oxide monomers, and cross-linking agents. Notably, the incorporation of tertiary amine oxide monomers (e.g., ODEA) significantly reduces nonspecific adsorption between the carrier and intestinal mucus. The small particle size of 5–200 nm facilitates easier penetration through the mucus layer and the intestinal epithelial cell barrier. In vitro experiments have confirmed that its mucus-penetrating ability and cellular internalization efficiency are significantly superior to those of traditional nanocarriers.

Meanwhile, the shell coordinates with boron nitride via electrostatic interactions, tightly encapsulating the core and effectively resisting erosion by gastric acid and digestive enzymes in the gastrointestinal tract. After incubation in simulated gastric and intestinal fluids, the core protein remains intact. 70% - 85% activity, successfully addressing the core challenge of poor oral stability in macromolecular drugs.

In terms of targeted delivery and therapeutic mechanisms,This technology establishes a closed-loop system of “ROS responsiveness + precise action,” significantly enhancing the specificity of treatment.

First, innovatively employing ROS-sensitive crosslinkers (e.g., BDD),The phenylboronic acid groups contained in this crosslinker undergo degradation in the high-concentration reactive oxygen species (ROS) microenvironment at the lesion site, thereby triggering the precise release of bioactive molecules from the core and avoiding side effects caused by nonspecific drug release in normal tissues. In vitro experiments demonstrated that the degradation rate of the carrier was significantly increased in the ROS-rich environment, with the drug release rate positively correlated with the level of oxidative stress at the lesion site, thus achieving “on-demand release at the target site.”

Secondly, the released antioxidant active molecules can directly scavenge excessive ROS at the lesion site.Reduce oxidative stress levels in intestinal tissues, while alleviating inflammatory responses and the severity of ulcers.In a murine model of ulcerative colitis, treatment with the nanocapsules significantly reduced the Disease Activity Index (DAI), restored colon length to near-normal levels, and returned reactive oxygen species (ROS) concentrations to baseline. In a model of radiation-induced enteritis, the nanocapsules effectively mitigated weight loss and markedly improved intestinal tissue damage.

Furthermore, this technology inClinical Utilityaspects possess“Multi-scenario adaptability + simple preparation”significant advantages.

In terms of scope of application,It can carry various bioactive molecules, such as proteins and nucleic acids, and is suitable for the treatment of gastrointestinal inflammatory conditions, including radiation-induced colitis and ulcerative colitis, as well as other diseases such as tumors and arthritis. Its formulations support multiple routes of administration, including oral and injectable, to meet diverse clinical needs.

In terms of the preparation process,Scalable production can be achieved through simple interfacial polymerization. The mild reaction conditions (4–37°C, pH 8–10) eliminate the need for complex equipment, thereby reducing industrialization costs.

In terms of safety,The carrier material exhibits excellent biocompatibility and shows no significant toxic side effects, laying a solid foundation for clinical translation.

Currently, to address the core challenges of “poor drug targeting, low bioavailability, and significant side effects” in the treatment of diseases such as inflammatory bowel disease and radiation-induced injury, biopharmaceutical companies and research translation platforms both in China and abroad are leveraging material innovations and formulation optimizations to advance precision therapy technologies from the laboratory to clinical practice, thereby meeting the needs of diverse scenarios including gastrointestinal inflammation and adjuvant cancer therapy.

Institute of Radiation Medicine, Chinese Academy of Medical SciencesIn response to the lack of pharmacological treatments for radiation enteritis, [we/the company] has developed and launchedNear-Infrared-Driven Self-Thermophoretic Nanomotors (H(x)MoO(3)(@)SA(@)COS). This technology employs hydrogenated molybdenum oxide as the hydrogen-storage core, coated with sodium alginate and chitooligosaccharides. It innovatively utilizes near-infrared light (808 nm) to trigger directional self-propelled motion, enabling efficient penetration of the intestinal mucus barrier and achieving precise delivery and sustained release of active hydrogen at inflammatory sites.

The core advantage of this technology lies in its ability to selectively scavenge highly reactive free radicals via active hydrogen, without the need for conventional drugs, while simultaneously modulating immune repair, intestinal barrier reconstruction, and microbiota balance. In mouse models, it has improved survival rates under lethal-dose irradiationIncreased from 10% to 80%. The related research findings were published in Nature Communications in October 2025 and are currently in the preclinical translation stage, providing a novel approach for the treatment of radiation enteritis.

Danish biopharmaceutical company Zealand PharmaFocusing on the targeted therapy needs for inflammatory bowel disease (IBD), in collaboration with the acquiredEncycle TherapeuticsLaunchCandidate Drug ET3764. This drug targets integrin α4β7. As a class of oral inhibitors synthesized via Encycle’s advanced biotechnology platform, it leverages the unique physicochemical properties of macrocyclic peptides and their advantage in modulating protein-protein interactions to precisely act on core adhesion molecules that mediate the migration of immune cells to gut-associated lymphoid tissues.

Its core advantage lies in its ability to selectively target key therapeutic targets in IBD, without relying on traditional broad-spectrum anti-inflammatory mechanisms. By inhibiting the adhesive function of integrin α4β7, it intervenes in the inflammatory process at the pathogenic level, while enhancing treatment convenience through oral administration.

The drug has passed preliminary R&D validation and been incorporated into Zealand Pharma’s peptide portfolio. Leveraging its expertise in peptide drug development and collaborative resources with leading global pharmaceutical companies, the company is advancing subsequent development. Currently in the translational research phase, it offers a novel direction for targeted peptide therapies in the treatment of inflammatory bowel disease.