Inhaled Therapeutics
Effective delivery to the lung represents a promising opportunity for many pulmonary and systemic diseases. Inhaled delivery of particle-based therapeutics holds tremendous potential for treating diseases, such as tuberculosis and cystic fibrosis, where delivery to specific regions of the lung and patient compliance are required.
By combining rationally designed PRINT particles with known small molecule and biological therapeutics, Liquidia is developing a new generation of inhaled therapeutics that offer enhanced delivery to specific regions of the lung based on the precise size, shape, and chemistry of the nanocarrier. More efficient and targeted delivery may lead to enhanced efficacy and optimized therapeutic index.
Combined, these characteristics may lead to reduced drug dosage and dosing frequency requirements, thereby minimizing systemic side effects and resulting in improved patient compliance. The application of PRINT particle delivery methods to biotherapeutics offers an effective non-invasive alternative to needle injections.
Liquidia’s inhaled PRINT particles are distinguished by:
- Precise control of particle size and shape - Precise control of particle size and shape facilitates predictable and controlled delivery to specific regions of the lung, including potentially the small airways and distal alveolar spaces which can be difficult to access with traditional technologies. In addition shape can be uniquely used to minimize aggregation, maximize airflow independence, and control drug release profiles.
- Monodisperse (i.e. uniform) particle mixtures - Unlike traditional nanoparticle production methods such as self-assembly and milling, which result in heterogeneous particle mixtures, the PRINT process yields particles that are highly uniform in size and shape. The monodispersity of PRINT particle mixtures reduces aggregation, increases fine particle dose, and facilitates more predictable biodistribution profiles and optimization for various therapeutic objectives.
- Neat Drug Profiles - Developing therapeutics of neat or"pure" drug (without excipients) may avoid potential toxicities and reduce additional development uncertainties
siRNA Delivery
The discovery of RNA interference (RNAi) has been widely heralded as the foundation for a major breakthrough in human therapeutics. RNAi is a novel mechanism that silences gene expression and inhibits protein production using molecules known as small interfering RNA (siRNA). Since the mechanism was discovered by Andrew Fire and Craig Mello in 1998, significant progress has been made towards the development of RNAi-based therapeutics for diseases, with several candidates in human clinical trials. However, to enable widespread adoption of siRNA therapeutics, safe and effective delivery vehicles are required to protect the delicate biological cargo and facilitate knockdown of target genes.
In the rapidly emerging field of siRNA delivery, Liquidia is developing PRINT nanoparticles to overcome barriers to effective systemic delivery in addition to unique approaches to local delivery. Systemic siRNA delivery, in particular, requires that particles have the ability to navigate the circulatory system and avoid uptake and clearance by non-target tissues. Upon leaving the bloodstream, the siRNA nanoparticles must diffuse through the extracellular matrix, be taken up into the target cell, and escape the endosome to reach the cytoplasm. Finally, the siRNA must be released from the carrier to induce gene knockdown, a process by which the expression of unwanted genes is reduced.
The ability to precisely tune multiple particle characteristics, including size, shape, surface functionality, and chemistry using PRINT technology offers significant advantages for unleashing the potential of siRNA-based therapeutics.
Next Generation Sequencing
Enabling rapid and accurate gene sequencing at a low cost represents a promising opportunity toward the advancement of personalized medicine. Next generation sequencing instruments provide different ways of achieving high throughput with reasonable cost. While these new technologies utilize different platforms and sequencing principles, many of these approaches require the use of micro-beads and/or wells with precise control of size, chemistry, surface functionality and porosity.
Liquidia's PRINT® technology can offer multiple benefits for next generation sequencing technologies including improved read accuracy, longer read length and faster reads, increased throughput and reduced cost.
These benefits are derived from inherent capabilities of the platform, including:
- Monodisperse particles: prepared from a molding based process, PRINT particles are truly mono-disperse and demonstrate excellent batch to batch consistency.
- Independent control of particle attributes: Micro-beads prepared by emulsion polymerization are typically limited in their capability to control all the critical design parameters. PRINT particles can independently optimize different particle attributes such as size, shape, composition, porosity and surface functionality.
- Patterned micro- and nano-wells with high fidelity and low cost: PRINT technology combines the precision of lithographic processes with the scale and economics of film-based manufacturing. Single nanometer precision has been achieved at low cost using a variety of replication materials. Multiple features of different size, shape, aspect ratio and packing density can be prepared in a single-step replication process with high fidelity.
- Additional dimensions for multiplexing: the unprecedented control of particle shape, as well as the unique format of high density particle arrays, may significantly decrease sample preparation time, provide additional dimensions for multiplexing, and enable new sequencing platforms that would be otherwise impossible.
Materials Science Applications
In the Materials Science sector, Liquidia utilizes PRINT technology to develop nano-precision patterned films for transformative energy efficient products in multiple sectors.
Liquidia's unique ability to manufacture high volumes of complex micro- and nanostructured films, from a variety of materials, offers novel solutions for precise light management and improved energy efficiency. Commercial scale production is made possible by a high throughput, roll-to-roll manufacturing process.
Liquidia is working independently and with partners to commercialize high-performance applications for the following markets:
Energy Storage
A significant need exists for next- generation batteries and supercapacitors with increased energy and power density that can be operated within a wide temperature range and at high operating voltage, while maintaining a long life cycle (greater than 10 years). Liquidia’s PRINT technology makes it possible to produce large volumes of nano-patterned electrode materials that may dramatically improve the efficiency of energy storage devices such as Li batteries.
Energy Efficient Building Materials
Energy expenditure on residential and commercial buildings exceeds hundreds of billions of dollars each year. Cool roof technologies and dynamic windows offer a promising solution to reducing building energy expenditures by selectively reflecting or absorbing solar radiation to promote heating or cooling. Liquidia’s PRINT® technology offers the unprecedented ability to fabricate highly precise nanoscale objects and features from virtually any material to produce dynamic or passive films that can selectively increase the reflection efficiency of roofing materials and windows. Combining the precision of the electronics industry with large area, high volume manufacturing, Liquidia is enabling a new generation of high efficiency, cost-effective, and aesthetically appealing materials for a variety of architectural applications.
Solid State Lighting
Solid-state lighting (SSL) promises to contribute to vast energy savings, especially as it is employed for general illumination applications. Energy savings realized from current LED and OLED lighting technologies could be significantly improved by using functional nano-featured film to extract trapped light within the SSL devices. Using PRINT® technology, Liquidia is focused on manufacturing nano-featured films, fabricated from high performance materials, that can be incorporated into SSL devices to increase efficiency, cost-effectiveness, and reliability. Ultimately, Liquidia’s scalable manufacturing process will facilitate rapid commercialization of high efficiency SSL devices.
Aerospace and Defense
Liquidia’s ability to produce cost-effective, large area nanostructured materials enables novel applications in aerospace and defense. High fidelity replication of high aspect ratio and/or complex features from unique materials can facilitate applications in stealth, security, stimuli responsive films, aerodynamic flow, advanced displays, and other areas of critical national need.
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