More importantly, through the proprietary treatment method developed by the research group, the density of silanol groups on the material’s surface reaches more than four times that of conventional silica materials.
This property endows the material with an unprecedentedly strong adsorption capacity for drug molecules, while also exhibiting a significant affinity for water molecules.
Based on this, the research team discovered a novel phenomenon: when crystalline drugs are mixed with this silica nanomaterial, the drug molecules are converted into an amorphous state and adsorbed onto the material’s surface under dry conditions; when the mixture is immersed in water, the material preferentially adsorbs water molecules, causing the drug molecules originally adsorbed on the material to be released and form a supersaturated drug solution. This demonstrates that water molecules have transformed from a solubility-limiting factor in the traditional sense into a solubilizing factor that promotes drug dissolution.
This discovery not only uncovers a new law governing the adsorption and desorption of substances on silica surfaces, but also provides a completely new solution to the bioavailability challenge of poorly soluble drugs.
It is expected to greatly improve the water solubility and bioavailability of drugs, enhance therapeutic efficacy, and potentially revitalize drug development projects that have been shelved due to solubility issues.
In addition, the research findings provide a theoretical basis and technical support for the design of more efficient drug carrier systems, boasting broad application prospects.
Recently, the relevant paper, entitled Enhancing drug solubility through competitive adsorption on silica nanosurfaces with ultrahigh silanol densities, was published in PNAS[1].
Figure | Related paper (Source: PNAS)
I. From Submission to Acceptance in Just 6 Weeks
Lei Xu stated, “This paper took only six weeks from submission to acceptance, which underscores the peer recognition of our work.”
Reviewers commented, “This study presents a technology that is significantly superior to existing methods, with performance improvements of up to two to three orders of magnitude in some cases, and it has the potential to become a next-generation drug delivery platform.”
They further noted that by increasing the density of silanol groups on the nanoparticle surface, the technology not only accelerates the release rate of hydrophobic drugs but also greatly boosts their release load. Combined with density functional theory calculations, the study is the first to thermodynamically validate the advantages of this process, standing in stark contrast to previous methods. They also believed this achievement is expected to exert a far-reaching impact on the pharmaceutical industry and drive the further development of hydrophobic drug delivery technologies.
First, it can be applied to targeted drug delivery systems.
As modern medical technology advances toward the era of precision medicine, the research and development (R&D) and application of targeted drugs have become a key direction for treating complex diseases (e.g., cancer, immune-related diseases). However, many novel targeted drugs, such as proteolysis-targeting chimeras (PROTACs) and small-molecule inhibitors, often face critical issues like poor solubility and low bioavailability due to their high specificity and complex molecular structures, which greatly limit their clinical application.
The team’s technology is based on molecular-level interactions, aligning perfectly with the R&D logic of targeted drugs. By developing silica nanomaterials with high silanol group density, it provides a brand-new delivery solution for these poorly soluble drugs. Preliminary experimental results show that the technology can significantly enhance the release efficiency and stability of CRBN E3 ligase ligand-based drugs. This delivery system is expected to become a standard component of next-generation precision medicine, facilitating the translation of more targeted drugs from the laboratory to the clinic.
Second, it enables the repurposing of poorly soluble drugs.
Many drug candidates shelved due to solubility issues may be revitalized by this technology. By converting them into a stable amorphous state and achieving efficient delivery, these “failed drugs” can re-enter clinical trials, shortening the new drug R&D cycle and reducing costs.
Third, it holds potential for the delivery of gene therapy and biologic drugs.
II. The “Tough” Shift in Research Direction and Entrepreneurial Journey
In recent years, with advances in scientific research and a deeper understanding of disease mechanisms, the R&D of new drug molecules has become increasingly complex and costly.
Particularly in the field of small-molecule drugs, although many candidates exhibit excellent efficacy at the cellular level, their high lipophilicity leads to poor water solubility, which often prevents them from achieving the expected effects in clinical trials.
Statistics show that approximately 60% to 70% of small-molecule drugs fail due to solubility issues [2]. This not only increases R&D costs but also delays the launch of new drugs.
This study was conducted against the backdrop of this critical challenge. Specifically, the research team aimed to develop a universal drug delivery system to improve the water solubility and bioavailability of poorly soluble drugs.
In this way, the team hopes to revitalize potentially effective drugs abandoned due to solubility problems and significantly boost the success rate of new drug R&D.
In addition, this delivery system is expected to shorten the drug translation cycle from the laboratory to the market and reduce R&D costs, thereby accelerating the development of innovative therapies and providing more treatment options for patients.
Initially, Lei Xu and his colleagues focused their research on exploring the mechanism underlying this phase transition. They discovered that when crystalline drugs are mixed with the team’s colloidal sphere assemblies, all the crystals are converted into an amorphous state.
Based on classical nucleation theory, the research group focused on altering pore size and designed a series of experiments to verify the relationship between drug nucleation and nanomaterials. However, they found that surface modification had a more significant impact on the experimental results than pore size.
Furthermore, as the experiments progressed, the research team began to notice that this modification method could not only alter the physical form of drugs but also significantly improve their solubility.
Subsequent studies demonstrated that under appropriate conditions, the modified drugs can achieve an extremely high supersaturated state. This was a major breakthrough for the team, as it meant a solution to the critical problems of many poorly soluble drugs.
During this period, the research group concentrated on optimizing the preparation process of nanomaterials and their effects on different drugs to identify the most effective formulations.
After confirming the technology’s effectiveness and broad applicability, the research team began to consider its commercialization. The first challenge they faced was translating the lab-scale technology into practical products.
Following initial successes and technological recognition, the research team founded the startup PharmaEase Tech Limited in 2023, dedicated to developing drug delivery solutions based on this technology.
According to introductions, PharmaEase Tech focuses on developing cutting-edge nanotechnology-based drug delivery solutions, particularly for addressing the challenges of poorly soluble drugs. The team’s core technology is derived from research on silica nanomaterials with high silanol group density, which can significantly improve drug solubility and bioavailability, thereby enhancing therapeutic efficacy.
Currently, the company is actively advancing product R&D and preclinical testing, with the goal of bringing this innovative technology to the market as soon as possible to benefit more patients.
The journey may seem smooth on the surface, but in reality, the team has overcome numerous obstacles. Initially, Lei Xu’s team was focused on fundamental physics research, operating in a research environment and with conditions vastly different from those it faces today.
Lei Xu still clearly remembers the first time the team conducted experiments based on theoretical hypotheses. Back then, the team set their goals with great confidence, but reality quickly dampened their spirits. Experiments failed one after another, and those days were filled with frustration.
In addition to internal challenges, the team faced immense external pressure. Investors raised constant doubts, worrying whether the technology could truly move beyond the laboratory. In the face of such pressure, the research team requested samples from commercial partners and used outstanding experimental results to demonstrate to investors that their technology still holds strong competitiveness when applied to commercial products.
Through these interactions, the research team not only gained investors’ trust and support but also received valuable feedback, which helped them further optimize the technology and business model.
Looking to the future, Lei Xu plans to collaborate with pharmaceutical companies to expand the technology to the latest drug R&D fields, including targeted drugs and biologic drugs.
References:
1.https://www.pnas.org/doi/10.1073/pnas.2423426122
1.D. V. Bhalani, B. Nutan, A. Kumar, A. K. Singh Chandel, Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics.Biomedicines10, 2055 (2022).