Gold and Silica Nanoparticles in Nanomedicine: Bridging the Gap Between the Bench and GMP
Scientist
on
August 24, 2023
This blog post was written by Kimberly Quart and Stephanie Morris from Fortis Life Sciences®. Fortis partners with diagnostics and life sciences companies to design, validate, and manufacture solutions to solve their complex development problems.
Nanomedicine is a rapidly advancing field that utilizes nanotechnology to revolutionize medical applications. At the nanoscale, materials exhibit unique properties that hold the potential to transform drug delivery, imaging, diagnostics and therapeutics. Among the various nanomaterials being explored, gold and silica nanoparticles have garnered significant attention due to their distinctive characteristics and their importance in nanomedicine. While the synthesis of these materials is widely performed during R&D at the bench scale, challenges associated with process development and scale-up often arise on the path to GMP manufacturing.
Challenges with Scaling Up Gold Nanoparticles
Gold nanoparticles have emerged as a versatile nanomaterial with a wide range of applications in nanomedicine. Their unique optical properties, particularly in the near-infrared range, make them valuable in photothermal therapies, imaging and theranostics, while their inherent biocompatibility and ability to be surface-modified has seen them used in drug delivery and gene therapy applications.
The size and shape of gold nanoparticles are often critical to the particles’ therapeutic function or properties for various applications – whether for targeting a narrow absorption profile, precisely controlling size to direct an uptake route or influence circulation time or triggering a particular biological response. During scale-up, it can be more challenging to achieve particle attributes that match those of small-scale reactions – i.e., average particle size might be larger or smaller – making additional evaluation and adjustments necessary. For many nanoparticle syntheses, temperature control and mixing rates are essential factors for controlling particle size and shape. Often, standard “off the shelf” equipment used for GMP fabrication and purification work in other spaces (i.e. CGT) are not designed to accommodate the unique tolerances and parameters required for reproducible, clinical-scale manufacturing of metal nanoparticles.
While physicochemical characteristics like size and optical properties are often high on the list for consideration during scale-up, another challenge with gold nanoparticles lies in their vulnerability to biological growth and contamination. Scaling up while ensuring low bioburden and/or including filtration becomes crucial for applications that require microbiological controls. When combined with the already challenging fabrication considerations covered in the previous paragraph, bioburden and sterility requirements drive a need for even more specialized fabrication and purification equipment and controls.
Challenges with Scaling Up Silica Nanoparticles
Silica nanoparticles, particularly mesoporous silica, have attracted significant interest in nanomedicine. Their high surface area, porous structure and high biocompatibility make them attractive candidates as drug carriers. Due to a very large library of commercially available silica precursor materials, silica nanoparticle surface chemistries are extremely customizable, making this particle platform readily translated across many nanomedicine-based applications.
The primary considerations when scaling up silica nanoparticles focus on particle attributes such as size, shape and pore structure. Like their gold counterparts, silica nanoparticles’ size and shape strongly influence characteristics such as circulation time and uptake route. With mesoporous silica, the pore structure is also critical-to-function – particular pore structures and sizes are optimized for a given application and need to be preserved throughout scale-up to maintain the end product’s desired function. Fabrication parameters such as heating rate, mixing rate and reagent addition rate are of particular importance in maintaining these key attributes.
Like gold nanoparticles, silica’s innate biocompatibility can allow for unwanted contamination and growth of biologics. There are several methods that can be implemented during fabrication to minimize contamination, but as discussed previously this becomes more challenging at-scale and can require specialized equipment.
Finding Balance
In both gold and silica nanoparticle development, balance is key. To avoid costly delays and budgetary overruns, manufacturers must prioritize critical quality attributes and understand which specifications are vital for successful product performance. For example, a bench-scale process to synthesize gold nanoparticles may consistently produce nanoparticles with an average diameter of 20 nm, while a scaled-up process for the same particle produces material with an average diameter of 24 nm. A first instinct may be to re-tool the scaled process until the output exactly matches the 20 nm output of the bench-scale process. This triggers an effort to review what parameters in the manufacturing process are most impactful on particle size and then design new processes to more tightly control that parameter. Such development work can incur high labor costs, additional equipment expenditures and force delays that result in missed clinical trial and funding timelines – all of this to address a tolerance in particle size that may not actually impact product performance.
A contract development and manufacturing organization (CDMO) with deep expertise in both nanomaterial development and manufacturing can guide clients through scenarios such as this. The right CDMO partner can design optimization and process development experiments that identify which specifications and associated tolerances are critical to product performance, and in turn, identify which manufacturing or processing parameters impact those specifications the most. By empirically identifying the right controls, the CDMO and client can find the right balance between designing robust manufacturing processes that eliminate scrap and reduce overall risk while also maintaining speed to clinic and budgetary constraints.
The Path Forward
Despite the challenges, the potential of gold and silica nanoparticles in nanomedicine is undeniable. As nanomedicine continues to thrive, addressing scale-up and process development challenges will be vital for driving innovation. Transitioning from promising ideas and successful laboratory studies to commercially viable products is no easy feat. Many nanomaterials fail to progress beyond the early stages of development due to the lack of a clear path and specialized expertise required to navigate the middle ground between research and commercialization.
At nanoComposix (a Fortis Life Sciences company), we play a critical role in supporting the transition from early-stage research to GMP manufacturing for Phase I and Phase II clinical trials, and beyond. We offer end-to-end contract services, supporting clients at any entry point, from early R&D and tech transfers, through scale-up, process development and manufacturing. With our technical expertise in both development and manufacturing commercialization, we provide invaluable support to companies looking to bring gold or silica nanoparticle-based nanomedicine technologies to fruition. Contact us to speak with one of our experts about your project today.