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Controlled Release Systems for Nanoparticles carrying RNAs

​​​​​​​​​​​​​​Systems designed for controlled release of RNA-carrying nanoparticles need to keep the nanoparticles intact until their release. This is decisive since non-encapsulated RNA cannot be taken up by the cells due to the high molecular weight and the multiple negative charge of free RNA.

This means that all nanoparticles relying on charge interaction require either non-charged or low charged matrices as release systems to prevent competitive decomplexation of the RNAs.

Controlled release via 3D printing

Dr. Dina B. MahmoudF​ollowing this design approach, we employed agarose as a hydrogel matrix that was 3D printed via extrusion to form the shell of a matrix encapsulating a core of Pluronic F127 carrying siRNA/Lipofectamine RNAiMax nanoparticles. Dr. Dina Mahmoud could control the release of RNA nanoparticles by the printing design, i.e. by the number of agarose layers as well as the distance between the printed hydrogel strands.​


team

​Dr. Dina B. Mahmoud developed this 3D printing approach.

literature

Mahmoud D , Wölk C & Schulz‐Siegmund M Fabrication of 3d printed, core‐and‐shell implants as controlled release systems for local sirna delivery. Adv Healthcare Materials. 2023;12(31). doi: 10.1002/adhm.202301643

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siRNA delivery from cross-linked gelatin microparticles

Dr. Franziska MitrachIn cooperation with ​​JProf. Dr. Michael C. Hacker we employ cross-linked gelatin microparticles for loading and release of siRNA-carrying nanoparticles. For nanoparticle loading, nanoparticles are dispersed in a small volume of medium and mixed with dried cross-linked gelatin microparticles in order to homogeneously load the nanoparticles into the microparticles.

For delivery, we assembled loaded micro​​particles with cells to form microtissues. The tight contact between cells and siRNA-loaded microparticles leads to efficient and homogeneous cell transfection with siRNA necessary for therapeutic use [1, 2].

literature

[1]Hinkelmann S, Springwald AH, Starke A, et al. Microtissues from mesenchymal stem cells and siRNA-loaded cross-linked gelatin microparticles for bone regeneration. Mater Today Bio 2022; 13: 100190. doi: 10.1016/j.mtbio.2021.100190

[2] Hinkelmann S, Springwald AH, Schulze S, et al. Mineralizing Gelatin Microparticles as Cell Carrier and Drug Delivery System for siRNA for Bone Tissue Engineering. Pharmaceutics 2022; 14. ​​​doi: 10.339​0/pharmaceutics14030548

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Layer by layer systems (LbL)

Dr. Jan KrieghoffPolyelectrolyte multilayers, more precise complexes between alternating polycation and polyanion layers, allow multiple possibilities to design different materials for pharmaceutical use. It is possible to produce surface coating as well as flexible films using automatized production as well as different combinations of polyelectrolytes. The fascination of polyelectrolyte multilayers is the ability to functionalize them with additional materials using electrostatic interactions. In our projects we functionalize polyelectrolyte multilayers with nucleic acid – lipid nanoparticles to design novel local release systems for nucleic acid therapeutics. 

VMaria Krabbesarious techniques are used to understand the structure of the polyelectrolyte multilayers, e.g. atomic force microscopy, fluorescence microscopy, water contact angle measurements, x-ray techniques. The work also includes the investigation of new loading strategies for the polyelectrolyte multilayers, like in our recent work ink-jet 3D printing. The hypothetical applications are can be seen in regenerative medicine, but also in other nucleic acid therapies. In a novel project we plan to apply the technique on urethral stents.

literature

Krabbes M, Kieckhöfer M, Schmidt C, et al. Inkjet printing of lipoplexes: A feasibility study. Applied Materials Today 2025; 44: 102699. doi: 10.1016/j.apmt.2025.102699

Krabbes M, Kampik V, Krieghoff J, et al. Development and functionality analysis of lipoplex-loaded polysaccharide-based surface coatings for local nucleic acid delivery. Int J Pharm 2025; 673: 125330. doi: 10.1016/j.ijpharm.2025.125330

Husteden C, Doberenz F, Goergen N, et al. Contact-Triggered Lipofection from Multilayer Films Designed as Surfaces for in Situ Transfection Strategies in Tissue Engineering. ACS Appl Mater Interfaces 2020; 12: 8963–8977.​ doi: 10.1021/acsami.9b18968

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