INTRODUCTION

Effective management of many chronic diseases, such as type 2 diabetes, often requires daily injections; however, this can negatively impact patient adher­ence. In the case of GLP-1 analogs, changing from daily to weekly injections has been shown to significantly improve adherence – behavior that persists over time.^¹

To address this burden of frequent dosing, the Swedish company Nanexa has developed PharmaShell^®, an innovative drug delivery system that uses nanometer-thin, inorganic coatings to turn short-act­ing drugs into long-acting injectables. By enabling a steady, extended release of medication from a single treatment, Phar­maShell can dramatically reduce dosing frequency.

The following details the PharmaShell technology and its benefits, with a focus on Nanexa’s recent Phase I clinical study, and its once-monthly type 2 diabetes GLP-1 re­ceptor agonist therapy.

PHARMASHELL TECHNOLOGY: ALD-ENABLED PRECISION COATING

PharmaShell encapsulates solid drug particles within an extremely thin, uniform coating made of an inorganic compound. The coating is applied using atomic layer deposition (ALD); a technique that deposits one atomic layer at a time in a gas phase reaction, Figure 1. ALD has many estab­lished applications in the semiconductor industry – but Nanexa is pioneering its use in drug formulation.

The process operates at mild temper­atures, protecting sensitive drug molecules while achieving subnano-level precision in coating thickness. Each particle is coated conformally, and the coating is only tens of nanometers thick, Figure 2.

The coating acts as a release rate-controlling barrier: once the PharmaShell-coated particles are injected into the body, the coating dissolves slowly or permits the drug to be released at a controlled rate. By adjusting the ALD parameters, Nanexa can precisely tailor the release profile of the drug, from days up to several months, without altering the drug molecule itself.

Nanexa’s ALD approach offers sev­eral technical advantages over conven­tional long-acting formulation methods. The ultra-thin coating means that each mi­crosphere is composed mostly of the active drug, not excipient. Drug loadings as high as 80% have been demonstrated with ALD-coated pharmaceutical powders, al­lowing a full therapeutic dose to be deliv­ered in a small injection volume.

The ALD coatings are also completely uniform and virtually free from imperfec­tions.² This uniformity ensures a smooth, predictable release of drug, minimizing the “burst release” often seen with biodegradable polymer microspheres (where an initial surge of drug can leak out too quickly). And importantly, because ALD is a gentle, solvent-free process, it can en­capsulate a wide range of molecules – in­cluding fragile peptides and proteins – without denaturing them.

THERAPEUTIC BENEFITS & APPLICATIONS OF PHARMASHELL

Reduced Treatment Burden & Better Outcomes
The key benefit of transforming a drug into a long-acting injectable (known as a depot medication) is that extending the dosing interval results in more stable disease control. Fewer injections mean greater convenience for patients, en­hanced adherence to medication, and im­proved health outcomes.1 In diabetes management, for example, consistent use of a GLP-1 agonist leads to better glycemic control and reduced risk of long-term complications.

Steady Therapeutic Levels
PharmaShell depots release the drug at a controlled rate, keeping plasma con­centrations within the optimal therapeutic window for an extended period. This avoids the peaks and troughs associated with frequent dosing. A smoother pharma­cokinetic profile can improve efficacy and tolerability. For instance, GLP-1 receptor agonists (the class including liraglutide) commonly cause gastrointestinal side ef­fects like nausea when the therapy is initiated at higher doses. With a controlled re­lease formulation, drug levels rise gradu­ally, potentially reducing such side effects during the initial period. In fact, in the first human trial of a PharmaShell-based ther­apy (NEX-22), no significant nausea or vomiting was observed even at high doses, suggesting that controlled release helped avoid the usual acute side effects.

High Drug Load, Low Injection Volume
Thanks to the minimal bulk added by the coating, a full monthly dose can often be administered in a volume of only a few tenths of a milliliter. This small volume can be injected with a very fine needle (around 30-gauge, similar to an insulin pen nee­dle) which improves patient comfort and acceptance. By contrast, some existing depot injections (such as certain micros­phere-based therapies) require thicker needles and syringe volumes due to the substantial amount of polymer or oil carrier. A less painful injection experience can make a big difference to whether patients are willing to start and continue long-term injectable therapy.

Broad Drug Compatibility & Stability
The PharmaShell platform has been evaluated across diverse drug classes – from small-molecule therapeutics to large peptides – and has consistently demon­strated the ability to modulate their release profiles. This suggests that the technology could be applied across a wide range of therapeutics where less frequent dosing is desired.

The robust inorganic coating also helps protect sensitive drugs from degra­dation until the moment of release. In cases where an active ingredient might otherwise break down quickly in the body, encasing it in a protective coating can pre­serve its stability and potency until it is de­livered to the target site over time. In this way, PharmaShell not only extends the ac­tion of drugs but can also enhance their effective lifespan in the body.

NEX-22: A ONCE-MONTHLY GLP-1 INJECTION

Nanexa’s lead internal program, NEX-22, exemplifies the capabilities of PharmaShell technology. NEX-22 is a long-acting formulation of liraglutide, a GLP-1 receptor agonist used to treat type 2 diabetes.

Liraglutide’s clinical benefits (improv­ing blood sugar and supporting weight loss) are well established but in its stan­dard form, but liraglutide must be injected every day due to its short half-life (~13 hours). The goal for NEX-22 is to deliver liraglutide in a single injection that main­tains its therapeutic effect for about one month. Achieving this would reduce roughly 30 injections to just one, a dra­matic improvement in convenience for pa­tients.

In the PharmaShell manufacturing process, microparticles of liraglutide are coated with a precise inorganic coating to create the NEX-22 formulation. Upon sub­cutaneous injection, the coated micropar­ticles form a depot in the subcutaneous tissue, slowly releasing liraglutide as the coating gradually dissolves. Early labora­tory and animal studies indicated that the concept works: the coated particles re­leased liraglutide steadily over several weeks. These promising preclinical results paved the way for human testing of NEX-22.

Clinical Evaluation of NEX-22
The first-in-human evaluation of NEX-22 was a Phase I, single-ascending-dose trial conducted in 2024-2025. It enrolled patients with type 2 diabetes to assess safety, tolerability, and pharmacokinetics of this long-acting formulation. Small groups of patients received a single sub­cutaneous injection of NEX-22 at increas­ing dose levels (each new group getting a higher dose than the previous) under close observation. Each participant was followed for over a month to track how long liraglu­tide remained in circulation and to monitor any side effects.

The results were extremely encourag­ing. At the highest dose tested (30 mg, far above a typical daily dose), a single injec­tion maintained serum drug levels for up to 42 days, Figure 3. In other words, NEX-22 successfully turned a medication that normally lasts less than a day into a once-per-month treatment. The pharmacoki­netic data showed no large initial burst release – peak blood concentrations were reached around 1-2 days after injection, and then declined gradually over the sub­sequent weeks. This indicates that the ALD-applied coating functioned as in­tended, releasing the drug evenly over time rather than dumping it quickly.

Equally noteworthy was the tolerability of NEX-22 in this trial. Patients experienced no serious adverse events and, in fact, al­most no systemic side effects. Notably, the common GLP-1 related side effect of nau­sea did not occur in any dose group – even at the highest dose – an outcome that underscores how the controlled release prevented the sharp peak levels that typi­cally trigger such effects. The only side ef­fects observed were mild, transient reactions at the injection site (such as slight redness or tenderness), which resolved within a few days. The clinical study thus provided proof-of-concept that Phar­maShell can convert an immediate release drug into a long-acting injectable without new safety concerns, paving the way for the next phase of development.

COMPARISON WITH OTHER LONG-ACTING TECHNOLOGIES

PharmaShell’s approach to creating injectable depots is distinct from traditional methods. The most common technology for multi-week release has been biodegradable polymer microspheres (for example, PLGA-based microspheres used in some weekly injections). While polymer microspheres have enabled long-acting formulations for certain drugs, they often exhibit an initial burst release and can re­quire relatively large needles due to the volume and particle size of the injection. In contrast, PharmaShell’s coating pro­vides a controlled and uniform release with essentially no burst phase, and the high drug payload relative to the coating allows use of fine needles, making injec­tions more comfortable.

Pharmaceutical companies have also developed implantable devices or solid implants that release drugs over months or even years. Examples include contracep­tive hormone implants or implantable GLP-1 pumps. Implants can provide long-term therapy but require a minor surgical procedure for insertion and removal, and they cannot be easily adjusted once in place. PharmaShell aims to hit a sweet spot: achieving multi-month drug delivery with a simple injection. There is no need for surgical removal – when the drug depot is exhausted, it simply dissolves away.

FUTURE OUTLOOK

With the success of the Phase I study, Nanexa is now preparing to advance into the next stages of clinical development. The company is also exploring partner­ships and licensing opportunities, reflect­ing the strong interest in the industry for long-acting injectable therapies. A once-monthly GLP-1 treatment would be a no­table breakthrough in type 2 diabetes care, and other pharmaceutical compa­nies are likewise investigating long-acting formulations for metabolic diseases.

Beyond diabetes, the PharmaShell platform is being applied to other thera­peutic areas. For instance, Nanexa has en­gaged in feasibility studies with major pharmaceutical partners to evaluate Phar­maShell on their proprietary compounds – a testament to the wider interest in this ap­proach to drug delivery.

To prepare for future commercializa­tion, Nanexa has begun scaling up the ALD coating process in its current GMP fa­cility, ensuring that production can meet anticipated demand while maintaining the precision and consistency required for in­dustrial application.

In conclusion, PharmaShell technol­ogy represents a significant innovation in the field of drug delivery. By enabling pre­cise control over drug release through atomic-level engineering, Nanexa offers a way to dramatically extend the action of existing medications without compromis­ing their safety or efficacy.

NEX-22, in particular, shows how a daily therapy can be reimagined as a once-monthly treatment, potentially im­proving patient quality of life and adher­ence. As this technology progresses through clinical development, it has the potential to create a new generation of long-acting injectable therapies that ben­efit patients, healthcare providers, and health systems alike.

REFERENCES 

1. Polonsky WH, et al. (2022). “Higher Rates of Persistence and Adherence in Patients with Type 2 Diabetes Initiating Once-Weekly vs Daily Injectable GLP-1 RAs (STAY Study).” Diabetes Therapy, 13(2): 175–187.
2. Sparrow N. (2015). “Atomic layer dep­osition technology finds path to med­ical market via drug-delivery systems.” PlasticsToday, July 7, 2015.
3. La Zara D, et al. (2021). “Drug pow­ders with tunable wettability by atomic and molecular layer deposition: From highly hydrophilic to superhydropho­bic.” Applied Materials Today, 22: 100945.

Dr. Anders Johansson serves as Head of Intellectual Property, Senior Scientist, and Co-Founder at Nanexa, where he is been employed since 2009. Dr Johansson holds both an MSc and a PhD in Chemistry from Uppsala University, Sweden. Prior to joining Nanexa, he gained experience as a patent consultant at the intellectual property firm Bjerkéns KB in Sweden.

Dr. Polla Rouf is Head of ALD R&D at Nanexa. Dr. Rouf leads the development of atomic layer deposition (ALD) coatings that enable controlled drug release, contributing to programs such as NEX-22. He earned a PhD in Materials Chemistry from Linköping University specializing in the ALD technology, and holds a MSc in Chemical Engineering from Uppsala University.

Dr. Joel Hellrup is Head of Pharmaceutical R&D at Nanexa AB, leading research and development of drug formulations and quality control. He is one of the key developers of the PharmaShell® technology and is named as an inventor on several patent applications. He holds a PhD in Pharmaceutical Sciences and an MSc in Pharmacy from Uppsala University, and has received the Young Investigator Award from the Controlled Release Society.