Research Field 5

Lehner, E. et. al., Journal of Drug Delivery Science and Technology 2024, Volume 99, 105972, https://doi.org/10.1016/j.jddst.2024.105972

Drug delivery to the inner ear presents a unique challenge due to the complex inner ear anatomy and its tight physiological barriers. This study investigates the degradation behavior of intracochlear drug delivery implants (IDDI) composed of dexamethasone and poly(lactic-co-glycolic acid) (PLGA) or polyethylene glycol–poly(lactic-co-glycolic acid) (PEG-PLGA), respectively. IDDI were incubated in artificial perilymph and implants’ degradation kinetics, morphological changes, water uptake behavior, and pH alterations were assessed. Microscopy revealed significant changes in appearance, with PLGA IDDI exhibiting rapid expansion, reaching up to 183 % in diameter and 185 % in length. PEG-PLGA implants showed gradual expansion, reaching a maximum of 178 % in diameter and 144 % in length. Despite these morphological changes, the IDDIs could still be applicable in terms of cochlear dimensions in combination with cochlear implants (CI) in humans or in a domestic pig animal model. © 2024 The Authors. Published by Elsevier B.V.

Alqaisi, M. et. al., Polymer Chemistry, 2024, 15, 2949 – 2958, https://doi.org/10.1039/D4PY00355A

The generation of nanosized compartments in single chain nanoparticles (SCNPs) is a promising approach to generate individualized confinement-zones on a small scale for drug-encapsulation or catalysis. We here report the synthesis and characterization of compartmented, fluorinated SCNPs generated by single-chain collapse of amphiphilic copolymers. Polyethylene glycol (PEG) functionalized monomers were utilized as hydrophilic moieties, while hydrophobic residues were introduced using different mole fractions of either aliphatic or fluorinated monomers. Single chain collapse and subsequently crosslinking via copper-catalyzed azide–alkyne click reactions in selective and non-selective solvents yields internally structured SCNPs with hydrodynamic radii of 2.5–5.8 nm. Reproduced with permission from the Royal Society of Chemistry

 Li, Z. et. al., ACS Macro Lett., 2023, 12, 10, 1384–1388, https://doi.org/10.1021/acsmacrolett.3c00493

Hydrogen-bonding (H-bonding) assembly incorporated with an aggregation-induced emission (AIE) capability can serve as a powerful tool for developing supramolecular nanomedicine with clear tumor imaging and smart therapeutic performance. We here report a H-bonded polymeric nanoformulation with an AIE characteristic toward smart antitumor therapy. To do so, we first design a structurally novel tetraphenylethylene (TPE)-based H-bonding theranostic prodrug, TPE-(FUA)₄, characterized by four chemotherapeutic fluorouracil-1-acetic acid (FUA) moieties arched to the TPE core. A six-arm star-shaped amphiphilic polymer vehicle, P(DAP-co-OEGEA)₆, is prepared, bearing hydrophilic and biocompatible POEGEA (poly(oligo (ethylene glycol) ethyl acrylate) segments, along with a hydrophobic and H-bonding PDAP (poly(diaminopyridine acrylamide)) segment. Thanks to the establishment of the DAP/FUA H-bonding association, incorporating the TPE-(FUA)₄ prodrug to the P(DAP-co-OEGEA)₆ vehicle can yield H-bond cross-linked nanoparticles with interpenetrating networks. For the first time, AIE luminogens are interwoven into a six-arm star-shaped polymer via an intrinsic H-bonding array of the chemotherapeutic agent FUA, thus imposing an effective restriction of TPE molecular rotations. Concomitantly, encapsulated photothermal agent (IR780) via a hydrophobic interaction facilitates the formation of nanoassemblies, TPE-(FUA)4/IR780@P(DAP-co-OEGEA)₆, featuring synergistic cancer chemo/photothermal therapy (CT/PTT). Copyright © 2023, American Chemical Society

Thümmler, J. F. et al., Chemical Communications, 2023, DOI https://doi.org/10.1039/D3CC03851C

NIR-fluorescent LCST-type single-chain nanoparticles (SCNPs) change their photophysical behaviour upon heating, caused by depletion of water from the swollen SCNP interiors. This thermoresponsive effect leads to a fluctuating photoacoustic (PA) signal which can be used as a contrast mechanism for PA imaging. Rublished with a permission of the Royal Society of Chemistry 2023.

Qiu, X. et al., Biomacromolecules, 2022, 4519–4531,

https://pubs.acs.org/doi/10.1021/acs.biomac.2c00656

Chemodynamic therapy (CDT) reflects an innovative cancer treatment modality. To enhance its relatively low therapeutic efficiency, rational combination with extra therapeutic modes is highly appreciated. Here, core-coordinated amphiphilic, elliptic polymer nanoparticles (Cu/CBL–POEGEA NPs) are constructed via the self-assembly of a glutathione (GSH)-responsive polymer–drug conjugate. Side-chain acylthiourea (ATU) motifs are affixed, which behave as ligands capable of coordinating Cu(II). Benefitting from the GSH-induced reduction reaction, Cu(II) is converted into Cu(I) and subsequently react with endogenous H₂O₂ to create ^•OH, realizing GSH-depletion-promoted CDT. Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Copyright © 2022, American Chemical Society.

Thümmler, J.F. et al., Chemical Communications, 2023, DOI https://doi.org/10.1039/D3CC03851C

NIR-fluorescent LCST-type single-chain nanoparticles (SCNPs) change their photophysical behaviour upon heating, caused by depletion of water from the swollen SCNP interiors. This thermoresponsive effect leads to a fluctuating photoacoustic (PA) signal which can be used as a contrast mechanism for PA imaging. Published with a permission of the Royal Society of Chemistry 2023.

Qiu, X. et al., Biomacromolecules, 2022, 4519–4531,

https://pubs.acs.org/doi/10.1021/acs.biomac.2c00656

Chemodynamic therapy (CDT) reflects an innovative cancer treatment modality. To enhance its relatively low therapeutic efficiency, rational combination with extra therapeutic modes is highly appreciated. Here, core-coordinated amphiphilic, elliptic polymer nanoparticles (Cu/CBL–POEGEA NPs) are constructed via the self-assembly of a glutathione (GSH)-responsive polymer–drug conjugate. Side-chain acylthiourea (ATU) motifs are affixed, which behave as ligands capable of coordinating Cu(II). Benefitting from the GSH-induced reduction reaction, Cu(II) is converted into Cu(I) and subsequently react with endogenous H₂O₂ to create ^•OH, realizing GSH-depletion-promoted CDT. Additionally, the disulfide bond endows GSH-responsive CBL release and provokes further GSH decline, finally realizing combined CDT/CT toward enhancing antitumor outcomes, and in vitro as well as in vivo studies indeed reveal remarkable efficacy. Copyright © 2022, American Chemical Society

Lechner E. et al., International Journal of Pharmaceutics, 2023, 123268,

https://doi.org/10.1016/j.ijpharm.2023.123268

There is growing need for new drug delivery sytems for intracochlear application of drugs to effectively treat inner ear disorders. In this study, we describe the development and characterization of biodegradable, triamcinolone-loaded implants based on poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol–poly(lactic-co-glycolic acid) (PEG-PLGA) respectively, prepared by hot-melt extrusion. PEG 1500 was used as a plasticizer to improve flexibility and accelerate drug release. PEG-PLGA implants showed an initial slow release rate over several days regardless of the amount of PEG added. Mathematical simulations of the pharmacokinetics of the inner ear based on the in vitro release kinetics indicate a complete distribution of triamcinolone in the whole human scala tympani, which underlines the high potential of the developed formulation. © 2023 The Authors. Published by Elsevier B.V.

Du, F., et al. Int. J. Pharmaceutics, 2022, DOI:https://doi.org/10.1016/j.ijpharm.2022.122023   

The polymer/solvent system poly (l-lactic acid)/ethyl butylacetylaminopropionate (PLLA/IR3535) is regarded as an insect-repellent-delivery system, serving, e.g., for fighting mosquito-borne tropical diseases. In this work, samples of the polymer/repellent system PLLA/IR3535 were prepared by 3D-printing. The experiments showed that it is possible to print 3D-parts containing up to 25 m% repellent, with an only minor loss of repellent during the printing process. The study successfully proved the applicability of the technology of extrusion-based 3D-printing for the preparation of polymer parts with a specific shape/design containing mosquito-repellent at a concentration which raises the expectation to be used as a repellent delivery-device.

Hilgeroth, P., et al. Polymers, 2022, DOI:https://doi.org/10.3390/polym14183742

Additive manufacturing has a wide range of applications and has opened up new methods of drug formulation, in turn achieving attention in medicine. We prepare and use styrene–isobutylene–styrene triblock copolymers (SIBS; Mn = 10 kDa–25 kDa, PDI 1,3–1,6) as a drug carrier for triamcinolone acetonide (TA), further processed by fused deposition modeling to create a solid drug release system displaying improved bioavailability and applicability. Continuous drug release and morphological investigations were conducted to probe the influence of the 3D printing process on the drug release, enabling 3D printing as a formulation method for a slow-release system of Triamcinolone.