Explore nanoparticle types, properties, and applications

Nanoparticles are a versatile class of materials engineered at the nanoscale, offering unique properties that can be precisely tailored for therapeutic applications. Their size, surface characteristics, and compositions allow for targeted interactions with biological systems, making them suitable carriers for drug delivery. Understanding the different types of nanoparticles, along with distinct properties and formulation strategies, is key to unlocking their potential in advanced treatments.

Using NanoAssemblr™ technology, you can develop a broad range of nanoparticle formulations varying in size, payload, and excipient characteristics. Our NanoAssemblr™ technology enables the development of a broad range of nanoparticle formulations, varying in size (20 to 200 nm), payload (e.g., nucleic acids, hydrophobic drugs), and excipient characteristics (e.g., charge and pH tuning). With the ability to iterate and tune particle characteristics quickly, researchers are finding new designs and opening possibilities for targets that were once difficult to reach, and drugs that would have previously taken longer to develop.

Overview of drug carriers

Table 1. Particle type, active ingredients, and carrier materials

Other particle types that have been developed on the NanoAssemblr™ platform include:

• Niosomes – non-ionic surfactant-based vesicle
• Nanolipomer – hybrid particles made of lipids and polymers
• Dendrimer nanoparticle – modular biodegradable dendrimer carrying miRNA

Liposomes

Liposomes are drug-delivery vehicles that can be formulated with a wide variety of natural, synthetic, and modified lipid species to deliver drugs and contrast agents.

Fig 1. Schematic of the inside of a liposome.

More than 15 liposomal drug and vaccine formulations are on the market for indications such as cancer, fungal infections, macular degeneration, and pain management. Liposomes are also being studied in clinical, preclinical, and basic research, including for applications such as:

• Drug delivery
• Gene delivery and transfection
• Contrast agents for medical imaging (e.g., ultrasound, MRI, and fluorescence)
• Precursors for lipid coatings (e.g., biosensors)
• Model cell membranes
   

How liposomes are formulated

Fig 2. Diagram of formulation of liposomes using NanoAssemblr™ technology.

1. An organic solvent with dissolved lipids and an aqueous solution is injected into the two inlets of the NxGen™ mixer.
2. With laminar flow, the two solutions do not immediately mix. Microscopic features engineered into the channels cause the two fluids to intermingle in a controlled and reproducible way. 
3.  Within 1 ms, the two fluids are completely mixed. This mixing causes a change in solvent polarity, which triggers the self-assembly of lipids into liposomes. 
4. Controlling the speed and ratio of fluid injection controls the size of the liposomes.

NanoAssemblr™ technology overcomes liposome formulation challenges

Table 2. Challenges and solutions in advancing liposome formulations

Lipid nanoparticles

Lipid nanoparticles are the most clinically advanced non-viral gene delivery system. They effectively deliver nucleic acids to cells in the body, addressing a key barrier in the development and use of genetic medicines. LNP open the door to new applications in genetic medicine, such as gene editing, rapid vaccine development, immuno-oncology, and the treatment of rare genetic and difficult-to-treat diseases — all of which are usually hindered by inefficiencies in nucleic acid delivery.

Fig 3. Schematic of the inside of nucleic acid-lipid nanoparticle.

Lipid nanoparticles offer many advantages over previous lipid-based nucleic acid delivery systems, including:

• High nucleic acid encapsulation efficiency and potent transfection
• Improved penetration into tissues to deliver therapeutics
• Low cytotoxicity and immunogenicity

These characteristics make LNP the optimal delivery system for nucleic acids. In 2018, the FDA approved the first RNAi drug (Patisiran) delivered via lipid nanoparticles.

How LNP are formulated for clinical use

Fig 4. Lipid nanoparticle formulation in NanoAssemblr™ technology (left) and how LNPs deliver nucleic acids (right).

1. An organic solvent containing dissolved lipids and an aqueous solution containing nucleic acids are injected into the two inlet channels of the NxGen™ cartridge.
2. Under laminar flow, the two solutions do not immediately mix, but microscopic features engineered into the channel cause the two fluids to intermingle in a controlled and reproducible way.
3. Within a millisecond, the two fluids are completely mixed, causing a change in solvent polarity that triggers the self-assembly of lipid nanoparticles loaded with nucleic acids.
4. Changing the speed and ratio of fluid injection controls the size of the lipid nanoparticles.

Once manufactured, lipid nanoparticles mimic low-density lipoproteins in the body, allowing them to be taken up by an endogenous cellular transport pathway to deliver nucleic acids to cells. Using pH-sensitive lipids allows LNP to release encapsulated nucleic acids into the cytoplasm when vesicle pH decreases.

NanoAssemblr™ technology offers key advantages in lipid nanoparticle production

Table 3. Challenges and solutions in advancing LNP production

Polymeric nanoparticles

Polymer-based nanoparticles can improve the efficacy, solubility, toxicity, bioavailability, and pharmacokinetic profile of a drug molecule.

Fig 5. Diagram of a naked nanoparticle.

Numerous polymeric nanoparticle applications are being developed, including:

• Biodistribution of chemotherapeutic agents in tumors to reduce off-target toxicity and widen the therapeutic window
• Encapsulation and delivery of biomolecules for genetic medicine, gene-editing, and immunotherapy
• Encapsulation and co-delivery of multiple APIs and/or image contrast agents for combination drug therapy

How polymeric nanoparticles are formulated

Fig 6. Diagram of formulation of polymer nanoparticles using NanoAssemblr™ technology.

Polymers in a solvent are mixed with an aqueous phase in the NxGen™ cartridge where rapid, homogeneous mixing ensures particles are formed under consistent conditions. Computer-controlled independent injection of both liquids allows mixing speed and mixing ratio to be easily dialed in to systematically optimize particle formation parameters.

Overcoming key challenges in advancing polymer nanoparticle formulations

Table 4. Challenges and solutions in advancing polymeric nanoparticle formulations

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Application note: Developing a scalable RNA-LNP drug product for clinical translation application note