Sequential multi-step flash nanoprecipitation process for producing stable nanoparticles with high core loadings

Background

Nanoparticles are critical across diverse industries, serving essential roles in targeted drug delivery, medical imaging, and cosmetics. Their effectiveness relies heavily on two fundamental parameters: physical size and core loading capacity. For medical applications, particles must ideally remain under 100 nanometers to navigate biological barriers. Simultaneously, there is a pressing need to maximize core loading, which is the fraction of the active ingredient within the particle. High core loading is vital because it delivers more active material per nanoparticle, significantly reducing the required dosage and improving product efficacy.

Despite this need, current formulation approaches face significant limitations. Traditional methods like emulsions and metal-organic frameworks inherently struggle with scalability and cannot achieve sufficiently high active material loadings. Furthermore, conventional rapid precipitation techniques are fundamentally constrained because precipitation and stabilization occur simultaneously in a single mixing step. By forcing core formation and protective shell stabilization to happen concurrently, these single-step processes cannot push core loadings above 50 percent without compromising structural integrity. Attempting to increase the active payload in these conventional systems inevitably leads to uncontrolled particle growth, aggregation, and a loss of critical nanoscale dimensions.

Technology

The sequential, multi-step Flash Nanoprecipitation (FNP) process is a continuous manufacturing solution separating the precipitation and stabilization phases of nanoparticle formation. Utilizing two distinct mixing chambers connected by a delay tube, the system precisely controls particle assembly. In the first chamber, a hydrophobic core material dissolved in an organic solvent mixes with an antisolvent, causing the core to nucleate. The mixture flows through the connecting tube, imposing a strict residence time of 10 to 10,000 milliseconds for optimal core formation. Finally, it enters a second chamber where an amphiphilic polymer stabilizer is introduced to encapsulate the core within a protective shell.

This technology is differentiated by overcoming the limitations of traditional single-step FNP methods, which struggle to exceed 50% core loading without compromising stability. By decoupling core formation from shell stabilization, this solution achieves ultra-high core loadings of up to 95% by weight while maintaining tightly controlled diameters between 20 and 500 nanometers. This exceptional loading capacity delivers more active material per nanoparticle, significantly reducing required dosages. Furthermore, the resulting nanoparticles exhibit remarkable long-term stability in aqueous solutions. Its scalable nature and broad compatibility with various hydrophobic actives make it a versatile platform for drug delivery and medical imaging.

Benefits

• Ultra-High Core Loading: Achieves core loadings of up to 95% by weight, enabling the delivery of more active ingredients per nanoparticle, which reduces required dosages and improves treatment efficacy.
• Precise Size Control: Consistently produces small, monodisperse nanoparticles (typically 20 to 500 nanometers) that are optimal for targeted drug delivery and medical imaging.
• Exceptional Long-Term Stability: Creates highly stable nanoparticles that resist aggregation and maintain their size for months in aqueous solutions.
• Scalable and Continuous Manufacturing: Utilizes a robust, continuous-flow dual-chamber process that is easily scalable for commercial pharmaceutical and industrial production.
• Broad Versatility: Highly adaptable for encapsulating a wide variety of hydrophobic actives, ion-paired complexes, and imaging agents using diverse stabilizers and solvents.
• Enhanced Material Performance: Improves the functional properties of encapsulated materials, such as enhancing the fluorescence of imaging agents for medical diagnostics.

Applications

• High-loading pharmaceutical drug delivery
• Medical imaging contrast agents
• Cosmetic active ingredient encapsulation
• Nutraceutical and food fortification
• Specialty ink and pigment manufacturing

Additional info

This sequential Flash Nanoprecipitation process utilizes two continuous mixing chambers separated by a delay tube to decouple nanoparticle nucleation from stabilization. Hydrophobic cores precipitate in the first chamber before entering a second chamber where amphiphilic stabilizers form a protective shell. By controlling residence times between 10 and 10,000 milliseconds, the system produces stable nanoparticles with core loadings up to 95% and diameters ranging from 20 to 500 nanometers.