DDF Drug Delivery & Formulation Summit 2026 / Berlin
Despite pronounced clinical toxicity and significant challenges in therapy management, the oral administration of Tacrolimus has been the worldwide standard of care for decades in rejection prophylaxis following solid organ transplantation.
Because Tacrolimus has a very narrow therapeutic window, one of the central questions in therapy management is how treatment safety can be improved and how therapeutic blood-level profiles can become more predictable.
This challenge was at the heart of Dr. Elke Horstkotte’s presentation at the Drug Delivery & Formulation Summit 2026 in Berlin.
Under the title “An Innovative Mucoadhesive Buccal Film Formulation for Tacrolimus”, Nucleus Medical GmbHpresented a revolutionary, globally unique, patent-protected therapeutic system for Tacrolimus: a mucoadhesive buccal film that releases the active substance unidirectionally into the tissue and subsequently into the systemic circulation. In doing so, the system is designed to bypass the well-known limitations of oral therapy, including low bioavailability, food-dependent blood levels, and high intra- and interindividual variability in blood concentrations.
In particular, intraindividual fluctuations in Tacrolimus blood levels represent a substantial risk for patients. Below the therapeutic window, patients may no longer be adequately protected against rejection, creating a potentially life-threatening situation. Above the therapeutic window, Tacrolimus is associated with pronounced clinical toxicity affecting various organs.
Buccal administration therefore represents the world’s first non-oral medication approach with the potential to significantly improve the safety and tolerability of long-term immunosuppressive therapy with Tacrolimus.
Tacrolimus has been a standard of care in immunosuppressive therapy since its approval in 1994. For many patients, this means lifelong treatment, usually twice daily, and until now primarily in oral form. This is precisely where one of the key challenges lies. Tacrolimus has a narrow therapeutic window: underdosing may compromise protection against rejection, while overdosing may be associated with toxicity. In addition, there are pronounced food effects, high interindividual variability, and the known limitations of oral absorption.
Nucleus addresses this significant medical need with what it positions as the world’s first non-oral Tacrolimus medication system. The principle is clear: Tacrolimus should no longer be absorbed primarily via the gastrointestinal tract, but instead enter the systemic circulation through the oral mucosa. This concept is based on groundbreaking findings from modern clinical microbiology and genetics, which suggest a close relationship between oral administration and clinical toxicity.
Key points from the presentation
1. Tacrolimus remains indispensable — but oral administration is challenging.
Tacrolimus is a highly effective standard drug in transplantation medicine. At the same time, its use is characterized by a narrow therapeutic window, blood-level fluctuations, food effects, and high variability. This creates a clear need for a new dosage form.
2. The route of administration may be a clinically relevant lever.
Nucleus is pursuing a non-oral approach: a buccal film system that adheres to the oral mucosa and is designed to release the active substance in a targeted manner. The strategic rationale is clear: when a drug is used lifelong, its administration must be as controlled and reproducible as possible.
3. The formulation is technologically demanding.
Tacrolimus is practically insoluble in water and chemically sensitive. Developing a buccal film therefore requires a matrix that embeds the active substance in a stable manner, remains dimensionally stable upon contact with saliva, provides mucoadhesive properties, and at the same time enables directed release toward the mucosa. The presentation made clear that such a film is not a simple galenic formulation, but a complex drug-delivery system.
4. The film system is based on a bilayer concept.
The development approach presented combines an active-substance-containing mucoadhesive matrix with a backing layer. The goal is unidirectional release toward the oral mucosa. This structure is central to the functionality of the system.
5. Nucleus is working according to a clear development roadmap.
The company was founded in 2019, began operations in 2020, and develops the product through a network-based model. The development plan includes, among other steps, human proof of concept, design freeze, and pivotal kinetic studies.
The presentation made one thing clear: innovation in pharmaceutical development does not arise solely from new molecules. It can also emerge where established active substances are made more usable through intelligent formulation and new routes of administration.
This is particularly relevant in lifelong therapies such as immunosuppression after organ transplantation. In this context, drug delivery is more than a technical question. It is about predictability, control, therapeutic safety margins, and ultimately the everyday practicability of a therapy that accompanies patients for many years.
With this development program, Nucleus stands for a clear idea:
Tacrolimus does not need to be reinvented. But the way Tacrolimus enters the body can be rethought.
Rethinking Tacrolimus delivery for lifelong immunosuppression.
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