https://researchdata.se/sv/catalogue Search results sv Double Emulsions Enable In Situ Generation of Permeation Enhancers for Oral Delivery of Peptides Hannah Pohlit¹,², Lingxiao Li², Estela Isabel Bini³, Dario Colucci³, Cristhian Fernando Salas Cotaquispe¹, Maja Sikström¹, Per Larsson²,⁴, Christel A.S. Bergström²,⁴, Shakhawath Hossain²,⁴, David J. Brayden³, Alexandra Teleki¹,²* ¹Department of Pharmacy, Science for Life Laboratory, Uppsala University, Sweden ²The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala University, Sweden ³School of Veterinary Sciences, University College Dublin, Ireland ⁴Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, Sweden * Corresponding author (alexandra.teleki@scilifelab.uu.se) Abstract Oral delivery of peptide therapeutics remains limited by gastrointestinal degradation and poor epithelial permeability. Here, water-in-oil-in-water (W/O/W) double emulsions produced by microfluidics were designed to co-encapsulate octreotide and medium-chain triglycerides, enabling digestion-triggered generation of permeation-enhancing fatty acids. Production parameters were systematically optimized to obtain stable, monodisperse droplets with defined core-shell morphology. The emulsions comprised an inner aqueous phase containing the payload, encapsulated within a Miglyol 812N oil phase stabilized by polyglycerol polyricinoleate (PGPR), and dispersed in an external aqueous phase stabilized by Tween 80, yielding droplets of ~190 μm with a single inner aqueous core (~78 μm). Lipolysis studies confirmed minimal fatty acid release under gastric conditions and substantial release of caprylic (C8) and capric (C10) acids during intestinal digestion, accompanied by release of encapsulated cargo. In differentiated Caco-2 monolayers, digested emulsions increased apparent permeability (Pₐₚₚ) of fluorescein isothiocyanate-dextran (FD-4) and octreotide in a fatty acid concentration-dependent manner. Immunostaining showed occludin redistribution under permeation‑enhancing conditions. Ex vivo studies in rat colonic mucosa using Ussing chambers demonstrated a ~4-fold increase in FD-4 permeability for the digested emulsions, comparable to matched concentrations of free fatty acids, while octreotide permeability remained unchanged. Coarse-grained molecular dynamics simulations revealed strong association of octreotide with mixed bile salt–fatty acid micelles, limiting its freely dissolved fraction, whereas FD-4 remained predominantly solvated, consistent with the experimental findings. This study demonstrates that digestion of structured double emulsions enables in situ generation of permeation enhancers while simultaneously releasing hydrophilic cargo, providing a formulation strategy for oral delivery of peptide therapeutics. Keywords Lipid-based formulation, Lipolysis, Permeation enhancers, Apparent permeability, Molecular dynamics simulations, Intestinal permeability Thu, 11 Jun 2026 00:00:00 GMT https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-31266466 https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-31266466 Uppsala universitet Hannah Pohlit Lingxiao Li Estela Isabel Bini Dario Colucci Cristhian Fernando Salas Cotaquispe Maja Sikström Per Larsson Christel A.S. Bergström Md Shakhawath Hossain David Brayden Alexandra Teleki Chronic inflammatory diseases may benefit from nanocarrier platforms that co-deliver hydrophobic anti-inflammatory drugs and imaging agents. Here, we report polymeric theranostic nanocarrier dispersions produced by flash nanoprecipitation (FNP) that encapsulate flame-made manganese-doped superparamagnetic iron oxide nanoparticles (SPIONs; Mn0.25Fe2.75O4) together with T‑5224, a model small-molecule inhibitor of the c‑Fos/c‑Jun activator protein‑1 (AP‑1) complex. We first mapped key formulation and process parameters governing dispersion properties, including PLA–PEG molecular weight, total solute concentration, solvent-to-antisolvent ratio, and SPION:polymer mass ratio. These studies identified conditions yielding smaller, narrowly distributed dispersions. Using the optimized formulation, T‑5224/SPION nanocarrier dispersions were purified by magnetic separation and exhibited hydrodynamic diameters Thu, 05 Mar 2026 00:00:00 GMT https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-31385350 https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-31385350 Uppsala universitet Hannah Pohlit Alex Eric Weber Shaquib Rahman Ansari Yael Suarez-Lopez Qianying Chen Christina Paraskeva Vasiliki Koliaraki Alexandra Teleki Oral drug delivery to specific lesions in the gastrointestinal (GI) tract remains a major challenge. The current systems depend on internal physiological triggers such as pH, enzymatic activity, and luminal pressure, which exhibit wide intra- and inter-patient variability. To address this, an ingestible capsule was developed to enable on-demand, site-specific drug release in response to an external alternating magnetic field (AMF), with ultrasound imaging used for real-time localization. The capsule is composed of a low-melting-point wax matrix embedded with superparamagnetic iron oxide nanoparticles (SPIONs), which generate heat upon AMF exposure, resulting in rapid wax melting and burst drug release. SPIONs exhibited no toxicity in zebrafish embryonic development, demonstrating excellent biocompatibility. Capsules were fabricated in a hemispherical shape using a 3D-printed mold, yielding highly reproducible batches with a mass variation within ±10%. A Design of Experiments (DoE) approach identified an optimized formulation comprising a 6:4 docosane:eicosane wax blend, 10 wt% SPION loading, and a 1.5 mm capsule shell thickness, achieving efficient magnetic heating while maintaining mechanical strength (> 2 N), sufficient for withstanding GI transit. The optimized capsule formulation exhibited no cytotoxicity in vitro and remained intact throughout sequential incubation in simulated gastric, intestinal, and colonic fluids. No drug leakage or significant metal leaching (≤ 0.6%) was obtained. The capsule was successfully visualized in a porcine abdominal model using a handheld ultrasound device commonly used at the bedside in the clinic. AMF exposure triggered complete drug release within 33 seconds in vitro. In vivo studies in mice further demonstrated capsule localization via ultrasound, and AMF-triggered capsule melting in the colon via endoscopy. In conclusion, this magnetothermal capsule platform integrates non-invasive imaging and externally triggered drug release to enable localized GI drug delivery, representing a promising strategy for precision treatment of GI diseases. Wed, 03 Sep 2025 00:00:00 GMT https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-30009196 https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-30009196 Uppsala universitet Yuming Zhang Kai Zhang Krisztina Juriga-Tóth Christina Paraskeva Peter T. Schmidt Vasiliki Koliaraki Alexandra Teleki The accurate prediction of the specific absorption rate (SAR) of superparamagnetic iron oxide nanoparticles (SPIONs) is critical for optimizing their performance in magnetic hyperthermia applications. This study presents the development of a predictive model for SAR using advanced machine learning techniques. A comprehensive dataset comprising 1,850 entries was compiled through the integration of 84 relevant scientific articles. The dataset listed 30 predictive features, including physical, chemical, and magnetic SPION properties, along with extrinsic experimental parameters commonly reported. Exploratory data analysis revealed complex nonlinear relationships among the predictive features. Twelve machine learning models were evaluated and refined using Bayesian hyperparameter optimization. The CatBoost algorithm emerged as the most effective model, achieving the lowest mean absolute error (20.92 W/g) and root mean squared error (39.41 W/g), along with a high coefficient of determination (R² = 0.98). Shapley Additive Explanation analysis identified the alternating magnetic field amplitude and frequency as the most influential factors, followed by SPION concentration and the surface area of the core nanoparticle. Conformal prediction analysis confirmed the model's reliability, providing a prediction interval of ±61.94 W/g. The model's generalization capability was validated using an independent dataset of SPIONs with varying sizes (from 7 nm to 30 nm) and dopants (Zn, Mn, Mg, and Co). The CatBoost model accurately predicted SAR values for small-sized nanoparticles (~7 nm), although predictions for medium (~15 nm) and large-sized (~30 nm) SPIONs exhibited greater variability. The study demonstrates that advanced machine learning models, such as CatBoost, can significantly contribute to the identification of nanoparticles with optimal properties for magnetic hyperthermia, thereby supporting their systematic and robust development for broader clinical use. Wed, 20 Aug 2025 00:00:00 GMT https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-29835419 https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-29835419 Uppsala universitet Edgar Vega Shaquib Rahman Ansari Jiaxi Zhao Yael Suarez-Lopez Alexandra Teleki Per Larsson Magnetic hyperthermia therapy using superparamagnetic iron oxide nanoparticles (SPIONs) offers a promising strategy for treating cancers resistant to chemo- and radiotherapy. However, oral delivery of SPIONs for localized treatment of gastrointestinal cancers has not been widely explored. Here, we report the development of methoxy polyethylene glycol (mPEG) functionalized SPIONs (mPEG-Mn0.6Zn0.4Fe2O4) engineered for oral administration with combined theranostic functionalities for magnetic hyperthermia treatment and magnetic resonance imaging (MRI) in colorectal cancer (CRC). The SPIONs achieved consistent heating performance in biorelevant colonic environments, exceeding a 5 °C temperature increase within 10 min under an alternating magnetic field (AMF). They also demonstrated superior r2 relaxivity compared to γ-Fe2O3, highlighting their potential as effective T2 MRI contrast agents. In vitro studies using CRC SW480 and Caco-2 cell lines assessed nanoparticle cytotoxicity, cellular uptake, and magnetic hyperthermia efficacy in both upright and inverted cell culture configurations. Magnetic hyperthermia induced significant CRC cell death in vitro, particularly in upright configurations, attributed to enhanced localized heating caused by nanoparticle sedimentation and enhanced SPION contact with cell surfaces. This emphasizes the importance of in vitro experimental parameters such as cell line, configuration, and AMF exposure time for systematic optimization of theranostic SPIONs during preclinical development. Finally, in vivo studies using a colorectal tumor xenograft mouse model demonstrated a marked therapeutic effect of magnetic hyperthermia by intratumorally injected SPIONs. The tumor volume was reduced by 63% following a single 20-minute AMF exposure. These findings demonstrate the potential of mPEG-Mn0.6Zn0.4Fe2O4 nanoparticles as a promising platform for non-invasive, image-guided magnetic hyperthermia therapy in CRC theranostics. Fri, 18 Jul 2025 00:00:00 GMT https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-27688668 https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-27688668 Uppsala universitet Yuming Zhang Christina Paraskeva Qianying Chen Anano Maisuradze Shaquib Rahman Ansari Tapati Sarkar Vasiliki Koliaraki Alexandra Teleki Superparamagnetic iron oxide nanoparticles (SPIONs) generate heat upon exposure to an alternating magnetic field (AMF) which has been studied for hyperthermia treatment and triggered drug release. This study introduces a novel application of magnetic hyperthermia to induce amorphization of a poorly aqueous soluble drug, celecoxib, in situ in tablets for oral administration. In situ amorphization can overcome the drug development hurdle of poor aqueous solubility by molecularly dispersing the drug in a polymeric network inside a tablet. However, current shortcomings of this approach include low drug loading in the tablets, toxicity of enabling excipients, and drug degradation. Here, SPIONs produced by flame spray pyrolysis are compacted with polyvinylpyrolidone and celecoxib, and exposed to an AMF. The degree of amorphization is strongly linked to the maximum tablet temperature achieved during AMF exposure, which depends on SPION composition and content in the tablets. Manganese ferrites exhibit no toxicity in human intestinal Caco-2 cell lines and are more effective than zinc ferrites in inducing complete amorphization of celecoxib. The resulting rapid dissolution and high solubility of in situ amorphized celecoxib in biorelevant intestinal fluid demonstrates the promising capability of SPIONs as enabling excipients to magnetically induce amorphization in situ in oral dosage forms. Fri, 18 Feb 2022 00:00:00 GMT https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-19154459 https://researchdata.se/sv/catalogue/dataset/doi-10-17044-scilifelab-19154459 Uppsala universitet Shaquib Rahman Ansari Alexandra Teleki Shno Asad Nele-Johanna Hempel Peter Svedlindh Korbinian Lobmann Christel AS Bergström