Editorial Article: Unchain your lipid nanoparticle development

Discover how to speed up high-throughput screening and production of lipid nanoparticles

21 Nov 2023

Eileen Hannigan and Sarah Nadin, Assay Development team at Merck
Sunshine by Unchained Labs

Lipid nanoparticles (LNPs) have made quite a name for themselves over the past few years, with a whole host of recent vaccine successes propelling them into the upper echelons of drug delivery mechanisms. Despite the elevated status of this truly game-changing technology, many labs are still making do with microfluidic equipment that isn’t specifically designed for high-throughput screening or production. This is leaving an unfortunate subset of researchers tied to time-consuming, inefficient, and costly workflows that are preventing them from taking full advantage of the enthusiasm surrounding LNPs. Fortunately, help is at hand in the form of Unchained Labs’ new Sunny Suite – comprising the Sunscreen formulation screener and the Sunshine process developer – designed to help lighten the load of LNP development and ultimately make the lives of researchers that little bit easier.

The pains of particle processing

Before shedding light on the benefits of the Sunny Suite, it’s worth taking some time to understand the pain points frequently encountered in LNP research. The creation of an ideal nanoparticle is anything but a quick process, typically involving hundreds of experiments to gain even the faintest glimpse of the formulation design space. Development doesn’t end there though, with multiple experimental iterations often required to hone in on areas of interest while shutting down avenues that are likely to lead to a dead end. Using traditional equipment to accomplish this can be incredibly inefficient, not least due to the manpower and time involved in the manual prepping, loading, running, unloading, and washing steps required for each individual experiment. This slow and laborious process can often render labs unable to reach double figures in terms of runs per day – a particularly harrowing thought considering how many iterations are needed to truly optimize LNP characteristics.

There is also the issue of consumables costs to contend with. Many platforms are still reliant on disposable microfluidic mixing cartridges that must be thrown away and replaced after each screening run, the cost of which can easily add up to many thousands of dollars over the course of a development program.

These challenges have left the scientific community crying out for purpose-built, high-throughput automation solutions that can unburden researchers from laborious, time-consuming, and expensive procedures. Fortunately, Unchained Labs has come to the rescue with its Sunny Suite screening and process development platforms, which operate symbiotically to create the ultimate LNP workflow.

Why apply Sunscreen?

Sunscreen is the first link in the Sunny Suite chain, designed to decimate the cost, time, and manpower involved in LNP screening. 96-well plates are the format of choice here, giving Sunscreen the capacity to generate 96 different formulations in a single automated protocol. There’s no need for complex coding either; Sunny Suite Software takes care of the entire process, even running sense checks to minimize the chance of failure. Simply enter your plate contents into the interface, decide which lipid-to-payload ratios and flow rates you’d like to run at, and then watch as the platform populates an entire batch of formulations in just six hours. Variability between runs can be disastrous for LNP development, which is why Sunscreen conducts automated washing protocols between each experiment, ensuring that poor formulations don’t have a knock-on effect on subsequent successful ones. Once the formulation protocols are complete, the Unchained Labs Stunner platform can be used to measure particle sizes, polydispersity, and payload concentration, creating a formidable workflow capable of producing and analyzing almost a hundred formulations in a single day.

Don’t forget your Sunnies

None of this would be possible without the Sunny, a reusable payload and lipid mixing device designed to be used time and time again rather than being thrown away after a single use. Eliminating disposable mixing cartridges from the equation can save labs literally thousands of dollars per experimental batch while minimizing the amount of waste sent to landfill. These microfluidic marvels come in several different designs to suit a wide variety of experiments, each one sporting a unique channel arrangement. Employing a solitary Sunny in place of multiple cartridges means that every single formulation will be mixed using the same device – removing the effect of geometric inconsistencies between cartridges that can affect encapsulation efficiencies and particle size – giving researchers an extra confidence boost that their results are valid.

Forecast: Sunshine

Speaking of Sunnies, the exact same Sunny used to screen LNP formulations in Sunscreen can then be directly transferred over to Sunshine for process development – along with researchers’ carefully optimized formulation protocols – eliminating the need for time-consuming revalidation procedures. Sunshine allows the rapid exploration of everything from lipid to payload ratios and flow rates to dilution factors and mixing options, with 10 experiments taking just 15 minutes. Sunny Suite Software is on hand once again to simplify the optimization of flow rate ratio, total flow rate, precursor volume, sample collection volume, and optional in-line dilution, making the synthesis of controlled, reproducible, and monodispersed nanoparticles a breeze.

Once the perfect formulation has been developed and it’s time to scale up, simply flip the switch to continuous flow mode and watch Sunshine generate tens of liters of product per day, all while maintaining a consistent particle size and polydispersity index. To satisfy even greater yield requirements, multiple Sunshine platforms performing identical protocols can be run side by side to increase output without the revalidation steps usually required for mass production. Sunshine truly bridges the gap between formulation screening and commercial-scale manufacturing in a single system solution, ensuring consistent particle sizes no matter the volumes produced.

A ray of hope

Put simply, Sunscreen and Sunshine are set to transform LNP research by eliminating the inefficient processes that still plague many labs. Whether it’s initial screening trials or process development, these cutting-edge platforms can reduce hands-on time, slash consumables budgets, and decimate experimental run times, while providing everything needed for efficient and consistent scale-up. Researchers are already enjoying groundbreaking LNP successes with equipment that isn’t specifically designed for the task, so imagine what could be achieved using high-throughput, automated screening and process development platforms that are. With the introduction of the SunnySuite, supercharged LNP formulation and process development is finally a reality.

This guest editorial article was written in conjunction with Dr. Ben Knappett, Product Manager – LNP Solutions at Unchained Labs.