Together with the Swiss company InnoMedica, @TheWackerLab at the National University of Singapore develops novel performance assays for injectable nanomedicines including their clinical drug candidate Talidox. The strategic collaboration within the Department of Pharmacy is supported by the National Research Foundation of Singapore and the Faculty of Science with a Resilience & Growth Postdoc Fellowship.
Our latest research article will appear in the journal Molecules soon. Here we explore the pharmacokinetics and in vitro properties of the drug formulations NanoCore-6.4 and NanoCore-7.4. Both polymeric nanocarrier formulations attract lipoproteins endowing them with a lipid-like biological identity. This leads to enhanced uptake in the brain. In the in vivo setting, the capacity of brain uptake depends on the drug release in the blood plasma that constantly reduces the payload of the carrier. Therefore, our simulations contribute to a better understanding of the brain delivery process, qualitatively and quantitatively. Furthermore, we were able to show that a small shift in the drug release had a considerable effect on pharmacokinetics. This is a way to measure the effectiveness of the loading strategy and allows a quality-by-design approach in carrier development.
Thanks to my great team, the #WackerLab has flourished! We moved our equipment twice and were completely digitalized during the Circuit Breaker. Now we are part of the new Wet Science Building Family. Our national and international collaborations have made us much stronger. Who would have known that you could use #ReleaseTesting to estimate the environmental impact of drug products? Also, our predictions of the performance of injectable drug products have reached the next level! We can do everything we want, as long as we are working together! #MerryVirtualChristmas #WackerLab #ReleaseTesting #ScienceIsInterdisciplinary #PeopleDoTheScience#NUSDepartmentOfPharmacy #FacultyOfScience #UnitedWeCan
We are very happy to announce that Ge Fiona Gao just got her second first-author paper accepted by the Journal of Controlled Release. Our investigation of the drug release from PLGA microspheres highlights the need for biorelevant conditions to simulate degradation effects and predict bioavailability. Our international team of authors from Germany, Singapore, and Japan established in vitro-in vivo correlations for two drug formulations of tacrolimus. The formulations were tested in biorelevant medium in presence of protein background using the DR technology. To establish the IVIVC, a drug recovery model and a membrane permeation model were used and the fraction released in the in-vitro system was calculated. Mechanistic understanding of the physiological processes was gained by means of an in-silico model reflecting the absorption mechanisms in the subcutaneous tissue. The interplay between release, drug diffusion, lymphatic transport, and degradation plays a key role in the performance of injectables that remain in the subcutaneous tissue for a longer time period. Once production is over, the manuscript will become available under:
Gao GF, Ashtikar M, Kojima R, Yoshida T, Kaihara M, Tajiri T, Shanehsazzadeh S, Modh H, Wacker MG (2020); Predicting drug release and degradation kinetics of long-acting microsphere formulations of tacrolimus for subcutaneous injection, J Control Release (Accepted for publication)
Established by the Max Planck Society in 1951, the Beilstein Institute is a non-profit organization promoting the chemical sciences. Today it publishes the free-of-charge Beilstein Journal of Nanotechnology. During the COVID pandemic, researchers made their results accessible in times of crisis and we all found value in science without barriers. This is why I am happy to support the foundation by giving the first in a series of Beilstein Talks. On the 18th of November 2020, 9 pm Singapore time (2 pm CET) I will present:
“Nanomedicine at the crossroads: Why good chemistry is not enough”
Please join the virtual event and hear my critical reflection on nanotechnology research and why interdisciplinary approaches are needed to improve current design strategies…
Everyone wants to have access to medicines! For many years, we know that an aging population together with the quality of life we got used to leads to higher consumption of pharmaceuticals. But there’s also a rising concern that pharmaceutical drugs pollute our planet. Environmental scientists do not hesitate to say how disappointed they are with the pharmaceutical industry. Many comments indicate a total lack of understanding of the way our healthcare system works. Once a medicine has passed the clinical trials and market approval has been granted by a national authority, a company has no freedom at all to “just change the recipe”. Along this line, nanotechnology has been described to have a strong negative impact on different ecosystems. So how are we saving our planet? Our latest research paper written by Fabian Jung was just accepted by Environmental Research. It uses release testing, a method commonly applied by the pharmaceutical industry in development, to select drug formulations that are likely to succeed during clinical trials. We are combining this technique with computer-based simulations (ISERA model) and a lifecycle assessment to pre-select the excipients used in production. Because we are stopping the use of non-sustainable excipients very early in drug development, we still have all the freedom we need to make medicines more sustainable. Additionally, we present the application of nanomaterials to reduce environmental pollution. To do so, we combine smart technologies to identify drug formulations that are effective and safe in patients without posing a risk to the environment.
The AAPS student chapter of the National University of Singapore organizes a symposium together with Monash University putting interdisciplinary research in the spotlight. The event takes place on the 23rd of September. What would be more inspiring than bright young minds presenting their vision of the future? Please watch out for the latest announcements of NUS Pharmacy.
Our latest research article on drug release testing of a long-acting depot formulation was just accepted by the International Journal of Pharmaceutics. This is great work by the young first author Ge Fiona Gao. One year ago she won a Best Abstract Award of the AAPS Annual Meeting, now she has done a tremendous job showing the influences of the physiological environment on formulations that remain at the injection site for several weeks. The release assay elucidated the influence of proteins on microparticle release and how they affect discrimination between different batches of drug products. Even without affecting solubility, proteins stabilize particles and may affect the performance in the subcutaneous tissue. A mechanistic model helped us to understand the influences of such parameters and formulation characteristics on pharmacokinetics. Why does it matter? Without understanding what are the major drivers of drug release there will always be a high risk of failure when testing new long-acting therapeutics for chronic diseases.
Today, our manuscript on the Physiologically-based Nanocarrier Biopharmaceutics (PBNB) Model was finally accepted for publication by the European Journal of Pharmaceutics and Biopharmaceutics. I explained the purpose of this model in my talk during the Explain-My-Research Virtual Conference in May 2020 and will go more into detail during a Live Webinar organized by Malvern Panalytical in July. Rather than providing a ‘convenient fit’ only, the model is designed to link the pharmacokinetics of nanocarriers to a physiologically-based distribution. Interesting parameters you may obtain with this model are, for example, the targeting capability and the mean residence time of the nanocarrier in the blood plasma. A lowered plasma concentration often indicates that more drug has been released from the carrier and is not available for targeting any more. The PBNB model recognizes such changes and calculates how much carrier-bounded drug is accumulated before this release happens. Expressed as a fraction of the total dose, this is the targeting capability (Ftarget) . The mean residence time of the carrier (MRTc) in the blood plasma indicates how much time the delivery system had for this accumulation process and is a marker for targeting accuracy.