Use of Microfluidizer™ Technology for the Production of Polymer Nanoparticles

This technical article provides an overview of polymer nanoparticle development and production using Microfluidizer® processing equipment. Microfluidizer has been recognized as an ideal technology for producing polymer nanoparticles. This application note provides an overview of polymer nanoparticle development and production using the Microfluidizer® homogenizer. Important factors to be considered while developing the process are also outlined. Microfluidizer has been recognized as an ideal technology for producing polymer nanoparticles. Polymer nanoparticles are used for the production of solid lipid nanoparticles (SLN). These SLNs can be used for developing cellular/molecular delivery.   .

Why Polymer Nanoparticles?

Over the past decade, there has been increasing interest in biodegradable polymer nanoparticles. Their benefits include: • Ability to deliver different therapeutic component combinations. • Capacity to target specific substances. • Ability to protect active components against degradative forces. • Capacity to control component release. • Option to include identification capabilities. • Ability to sterilize through filtration.

Step 1: Define the Formulation:

Aqueous phase: Water + Surfactant

The most commonly used surfactant is polyvinyl alcohol (PVA), but some researchers have achieved successful results using polymeric surfactants such as polysorbate and polyoxyethylene or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) phospholipids. Surfactant concentrations are typically quite low. Concentration ranges from 0.1% to 1%.

Oil phase

Water-immiscible solvent + polymer + other components (active substances, contrast agents, etc.) should be included. The most commonly used solvents are ethyl acetate and methylene chloride. When selecting a solvent, there are various factors to be considered:

Water Miscibility

In general, the less miscible with water, the better. When water miscibility is high (ethyl acetate dissolves at 8.3 g/100 mL concentration), most researchers saturate the aqueous phase with solvent.

Boiling Point

Solvents are typically removed from the environment by evaporation. While solvents with low boiling points are easier to remove, processing may be more difficult. When working with highly volatile solvents (for example, dichloromethane has a boiling point of 39°C), it is critical to keep the sample cold throughout all stages of processing to prevent solvent loss due to rapid temperature increase.

Toxicity

There are solvents with excellent properties for this type of application; however, they are carcinogenic and cause reproductive system disorders like chloroform and DCM. The most commonly used polymer is poly(lactic-co-glycolic acid) (PLGA). Various PLGA types can be used to take advantage of critical properties such as polymer dissolution rate and compatibility with active substances. Molecular weight and the ratio of lactic acid to glycolic acid can be controlled. Additionally, PLGA copolymers can be used to provide specific properties. Chitosan copolymers can be used to target specific parts of the body. Researchers have even bound active components to the polymer. Other biodegradable polymers such as polycaprolactone (PCL) and polyesters have also been used. Many types of materials can be encapsulated with polymers.

Active Pharmaceutical Ingredients (APIs)

Due to the flexibility of polymer nanoparticles, APIs have been developed for many different indications. It is common practice for researchers to use different active components together. Compatibility of these components with the polymer is critical.

Diagnostic Agents

Contrast enhancers can be wrapped with particles containing active components. They can be used to confirm delivery of the active component load to the desired location. Combined use of therapeutic and diagnostic agents is addressed in the field of theranostics (combined diagnostic and therapeutic use).

Other Components

There are many other components used for different purposes. Researchers have used paramagnetic particles for proper targeting. Others have used activated metal oxides to provide targeted heat therapy.

Step 2: Define the Process Add the oil phase to the aqueous phase.

Mix using a rotor-stator mixer to create a stable pre-emulsion. This pre-emulsion must remain stable for an extended period to be processed with the Microfluidizer. Process the pre-emulsion using Microfluidizer™. Critical processing parameters are chamber type, processing pressure, temperature, and number of passes.  

Step 3: Solvent Extraction

Once nanoparticles are formed, there are various ways to remove the solvent from the formulation. One method is to allow the solvent to evaporate in a fume hood during mixing. Other methods typically require the use of various solvent exchange techniques such as separatory funnels or Büchi Rotary evaporators.  

Analysis Techniques

  Polymer nanoparticles are typically analyzed using particle size analysis. Dynamic light scattering is frequently used due to its ability to measure distinctly small particles. Optical microscopy as well as SEM or TEM can be used to analyze particles.  

Results

As shown in the particle size distribution map and data, the polymer droplet size is reduced from 181 nm after one pass to 133 nm after five passes through the Microfluidizer.    

Other Applications of Polymer Nanoparticles

Microfluidic technology can also be used to create pores in polymers that can be used to encapsulate water-absorbing processes.  

Conclusion

The importance of particle distribution in polymer nanoparticles, which have a wide range of applications, is well known. Polymer nanoparticles that achieve homogeneous distribution can find applications in many fields and create potential for new application areas. Microfluidics systems can provide the expected homogenization in terms of particle size distribution, and it has been observed that the resulting homogeneous emulsion/suspension can meet the required shelf life. Microfluidics systems can be used in different fields and successful results have been published. Erkan Mankan / Sales and Marketing Coordinator / Anamed Analitik ve Medikal Sistemler A.Ş.