1,045 results on '"Storm, G."'
Search Results
2. Osteoimmunomodulatory GelMA/liposome coatings to promote bone regeneration of orthopedic implants
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Jahanmard, F. (author), Khodaei, A. (author), Flapper, Jasper (author), Dogan, O. (author), Roohi, K. (author), Taheri, P. (author), Weinans, Harrie (author), Storm, G. (author), Croes, M. (author), Mastrobattista, E. (author), Amin Yavari, S. (author), Jahanmard, F. (author), Khodaei, A. (author), Flapper, Jasper (author), Dogan, O. (author), Roohi, K. (author), Taheri, P. (author), Weinans, Harrie (author), Storm, G. (author), Croes, M. (author), Mastrobattista, E. (author), and Amin Yavari, S. (author)
- Abstract
Despite being the most widely used biomaterials in orthopedic surgery, metallic implants do not induce new bone growth because they are bioinert. Surface biofunctionalization of implants with immunomodulatory mediators is a recent approach to promote osteogenic factors that facilitate bone regeneration. Liposomes (Lip) can be used as a low-cost, efficient and simple immunomodulator to stimulate immune cells in favor of bone regeneration. Even though liposomal coating systems have been reported previously, their main disadvantage is their limited ability to preserve liposome integrity after drying. In order to address this issue, we developed a hybrid system in which liposomes could be embedded in a polymeric hydrogel namely gelatin methacryloyl (GelMA). Specifically, we have developed a novel versatile coating strategy using electrospray technology to coat implants with GelMA/Liposome without using adhesive intermediate layer. The two differently charged Lip (i.e., anionic and cationic) were blended with GelMA and coated via electrospray technology on the bone-implant surfaces. The results showed that the developed coating withstood mechanical stress during surgical replacement, and Lip inside GelMA coating stayed intact in different storage conditions for a minimum of 4 weeks. Surprisingly, bare Lip, either cationic or anionic, improved the osteogenesis of human Mesenchymal Stem Cells (MSCs) by inducing pro-inflammatory cytokines, even at a low dosage of Lip released from the GelMA coating. More importantly, we showed that the inflammatory response could be fine-tuned by selecting the Lip concentration, Lip/hydrogel ratio, and coating thickness to determine the timing of the release such that we can accommodate different clinical needs. These promising results pave the way to use these Lip coatings to load different types of therapeutic cargo for bone-implant applications., Team Peyman Taheri
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- 2023
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3. Osteoimmunomodulatory GelMA/liposome coatings to promote bone regeneration of orthopedic implants
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ORT Research, Regenerative Medicine and Stem Cells, Researchgr. Beeldg. Moleculaire Interv., Orthopaedie Onderzoek, Jahanmard, F., Khodaei, A., Flapper, J., Dogan, O., Roohi, K., Taheri, P., Weinans, H., Storm, G., Croes, M., Mastrobattista, E., Amin Yavari, S., ORT Research, Regenerative Medicine and Stem Cells, Researchgr. Beeldg. Moleculaire Interv., Orthopaedie Onderzoek, Jahanmard, F., Khodaei, A., Flapper, J., Dogan, O., Roohi, K., Taheri, P., Weinans, H., Storm, G., Croes, M., Mastrobattista, E., and Amin Yavari, S.
- Published
- 2023
4. Docosahexaenoic acid liposomes for targeting chronic inflammatory diseases and cancer: an in vitro assessment
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Alaarg A, Jordan NY, Verhoef JJF, Metselaar JM, Storm G, and Kok RJ
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Nanomedicine ,Liposomes ,Docosahexanoic acid ,PUFA ,Inflammation ,Cancer ,Medicine (General) ,R5-920 - Abstract
Amr Alaarg,1,2 Nan Yeun Jordan,1 Johan JF Verhoef,1 Josbert M Metselaar,2,3 Gert Storm,1,2 Robbert J Kok1 1Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, 2Department of Biomaterials Science and Technology, Institute for Biomedical Technology and Technical Medicine (MIRA), University of Twente, Enschede, the Netherlands; 3Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany Abstract: Inflammation, oxidative stress, and uncontrolled cell proliferation are common key features of chronic inflammatory diseases, such as atherosclerosis and cancer. ω3 polyunsaturated fatty acids (PUFAs; also known as omega3 fatty acids or fish oil) have beneficial effects against inflammation upon dietary consumption. However, these effects cannot be fully exploited unless diets are enriched with high concentrations of fish oil supplements over long periods of time. Here, a nanomedicine-based approach is presented for delivering effective levels of PUFAs to inflammatory cells. Nanoparticles are internalized by immune cells, and hence can adequately deliver bioactive lipids into these target cells. The ω3 FA docosahexaenoic acid was formulated into liposomes (ω-liposomes), and evaluated for anti-inflammatory effects in different types of immune cells. ω-Liposomes strongly inhibited the release of reactive oxygen species and reactive nitrogen species from human neutrophils and murine macrophages, and also inhibited the production of the proinflammatory cytokines TNFα and MCP1. Moreover, ω-liposomes inhibited tumor-cell proliferation when evaluated in FaDu head and neck squamous carcinoma and 4T1 breast cancer cells in in vitro cultures. We propose that ω-liposomes are a promising nanonutraceutical formulation for intravenous delivery of fish oil FAs, which may be beneficial in the treatment of inflammatory disorders and cancer. Keywords: nanomedicine, PUFA, inflammation, cancer, fish oil, delivery
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- 2016
5. Liposomal docosahexaenoic acid halts atherosclerosis progression
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Chong, S Y, primary, Wang, X, additional, Van Bloois, L, additional, Huang, C, additional, Yu, X, additional, Sayed, N, additional, Zhang, S, additional, Ting, H J, additional, Thiam, C H, additional, Lim, S Y, additional, Lim, H Y, additional, Zharkova, O, additional, Angeli, V, additional, Storm, G, additional, and Wang, J W, additional
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- 2022
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6. Targeting of a platinum-bound sunitinib analog to renal proximal tubular cells
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Dolman MEM, Harmsen S, Pieters EHE, Sparidans RW, Lacombe M, Szokol B, Őrfi L, Kéri G, Storm G, Hennink WE, and Kok RJ
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Medicine (General) ,R5-920 - Abstract
ME (Emmy) M Dolman1, Stefan Harmsen1, Ebel HE Pieters1, Rolf W Sparidans2, Marie Lacombe3, Bálint Szokol4, László Orfi4, György Kéri4, Gert Storm1, Wim E Hennink1, Robbert J Kok11Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; 2Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands; 3Kreatech Biotechnology BV, Amsterdam, The Netherlands; 4Vichem Chemie Ltd, Budapest, HungaryBackground: Activated proximal tubular cells play an important role in renal fibrosis. We investigated whether sunitinib and a kidney-targeted conjugate of sunitinib were capable of attenuating fibrogenic events in tubulointerstitial fibrosis.Methods: A kidney-targeted conjugate was prepared by linkage of a sunitinib analog (named 17864) via a platinum-based linker to the kidney-specific carrier lysozyme. Pharmacological activity of 17864-lysozyme was evaluated in human kidney proximal tubular cells (HK-2); the capability of the kidney-directed conjugate to accumulate in the kidneys was studied in mice. Potential antifibrotic effects of a single-dose treatment were evaluated in the unilateral ureteral obstruction (UUO) model in mice.Results: The 17864-lysozyme conjugate and its metabolites strongly inhibited tyrosine kinase activity. Upon intravenous injection, 17864-lysozyme rapidly accumulated in the kidneys and provided sustained renal drug levels for up to 3 days after a single dose. Renal drug level area under the curve was increased 28-fold versus an equimolar dose of sunitinib malate. Daily treatment of UUO mice with a high dose of sunitinib malate (50 mg/kg) resulted in antifibrotic responses, but also induced drug-related toxicity. A single dose of 17864-lysozyme (equivalent to 1.8 mg/kg sunitinib) was safe but showed no antifibrotic effects.Conclusion: Multikinase inhibitors like sunitinib can be of benefit in the treatment of fibrotic diseases, provided that their safety can be improved by strategies as presented in this paper, and sustained renal levels can be achieved.Keywords: drug delivery, sunitinib, fibrosis, platinum linker
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- 2012
7. A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy
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Crielaard BJ, van der Wal S, Lammers T, Le HT, Hennink WE, Schiffelers RM, Storm G, and Fens MHAM
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Medicine (General) ,R5-920 - Abstract
Bart J Crielaard1, Steffen van der Wal1, Twan Lammers2, Huong Thu Le1, Wim E Hennink1, Raymond M Schiffelers1, Gert Storm1, Marcel HAM Fens11Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; 2Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany The first two authors contributed equally to this work. Abstract: Colchicinoids are very potent tubulin-binding compounds, which interfere with microtubule formation, giving them strong cytotoxic properties, such as cell mitosis inhibition and induction of microcytoskeleton depolymerization. While this makes them promising vascular disrupting agents (VDAs) in cancer therapy, their dose-limiting toxicity has prevented any clinical application for this purpose. Therefore, colchicinoids are considered attractive lead molecules for the development of novel vascular disrupting nanomedicine. In a previous study, a polymeric colchicinoid prodrug that showed favorable hydrolysis characteristics at physiological conditions was developed. In the current study, this polymeric colchicinoid prodrug was evaluated in vitro and in vivo for its toxicity and vascular disrupting potential. Cell viability studies with human umbilical vein endothelial cells, as an in vitro measure for colchicine activity, reflected the degradation kinetics of the prodrug accordingly. Upon intravenous treatment, in vivo, of B16F10 melanoma-bearing mice with colchicine or with the polymeric colchicinoid prodrug, apparent vascular disruption and consequent tumor necrosis was observed for the prodrug but not for free colchicine at an equivalent dose. Moreover, a five-times-higher dose of the prodrug was well tolerated, indicating reduced toxicity. These findings demonstrate that the polymeric colchicinoid prodrug has a substantially improved efficacy/toxicity ratio compared with that of colchicine, making it a promising VDA for cancer therapy. Keywords: colchicine, prodrug, nanomedicines, cancer, vascular disrupting agents
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- 2011
8. Port wine stain treatment outcomes have not improved over the past three decades
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van Raath, M I, Chohan, S, Wolkerstorfer, A, van der Horst, C M A M, Storm, G, Heger, M, Afd Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Pharmaceutics, Dermatology, Plastic, Reconstructive and Hand Surgery, ACS - Diabetes & metabolism, AMS - Restoration & Development, ACS - Atherosclerosis & ischemic syndromes, Afd Pharmaceutics, Sub Membrane Biochemistry & Biophysics, Pharmaceutics, and Biomaterials Science and Technology
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Pediatrics ,medicine.medical_specialty ,Treatment outcome ,Port-Wine Stain/therapy ,Port-Wine Stain ,MEDLINE ,UT-Hybrid-D ,Patient characteristics ,Lasers, Dye ,Dermatology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Dermatosurgery and Laser Dermatology ,0302 clinical medicine ,medicine ,Humans ,Laser Therapy/methods ,Lasers, Dye/therapeutic use ,business.industry ,Lasers ,Laser treatment ,Standard treatment ,Dye/therapeutic use ,Port-wine stain ,medicine.disease ,3. Good health ,Infectious Diseases ,Pharmacological interventions ,Treatment Outcome ,Quartile ,Photochemotherapy ,030220 oncology & carcinogenesis ,Original Article ,Laser Therapy ,business - Abstract
Background Since the early ‘80s, the pulsed dye laser has been the standard treatment tool for non‐invasive port wine stain (PWS) removal. In the last three decades, a considerable amount of research has been conducted to improve clinical outcomes, given that a fraction of PWS patients proved recalcitrant to laser treatment. Whether this research actually led to increased therapeutic efficacy has not been systematically investigated. Objective To analyse therapeutic efficacy in PWS patients globally from 1986 to date. Methods PubMed was searched for all available PWS trials. Studies with a quartile percentage improvement scale were included, analysed and plotted chronologically. Treatment and patient characteristics were extracted. A mean clearance per study was calculated and plotted. A 5‐study simple moving average was co‐plotted to portray the trend in mean clearance over time. The data were separately analysed for multiple treatment sessions in previously untreated patients. Results Sixty‐five studies were included (24.3% of eligible studies) comprising 6207 PWS patients. Of all patients, 21% achieved 75–100% clearance. Although a few studies reported remarkably good outcomes in a subset of carefully selected patients, there was no upward trend over time in mean clearance. Conclusion The efficacy of PWS therapy has not improved in the past decades, despite numerous technical innovations and pharmacological interventions. With an unwavering patient demand for better outcomes, the need for development and implementation of novel therapeutic strategies to clear all PWS is as valid today as it was 30 years ago.
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- 2019
9. Behavioral Interactions of Penned Red and Arctic Foxes
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Rudzinski, D. R., Graves, H. B., Sargeant, A. B., and Storm, G. L.
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- 1982
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10. Daytime Retreats and Movements of Skunks on Farmlands in Illinois
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Storm, G. L.
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- 1972
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11. Dispersal and Mortality of Red Foxes
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Phillips, R. L., Andrews, R. D., Storm, G. L., and Bishop, R. A.
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- 1972
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12. Effect of Mestranol and Diethylstilbestrol on Captive Voles
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Storm, G. L. and Sanderson, Glen C.
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- 1970
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13. Movements and Activities of Foxes as Determined by Radio-Tracking
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Storm, G. L.
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- 1965
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14. Movements of a Striped Skunk Infected with Rabies
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Storm, G. L. and Verts, B. J.
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- 1966
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15. Liposome induction of CD8+ T cell responses depends on CD169+ macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion
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Afd Pharmaceutics, Pharmaceutics, Grabowska, J, Affandi, A J, van Dinther, D, Nijen Twilhaar, M K, Olesek, K, Hoogterp, L, Ambrosini, M, Heijnen, D A M, Klaase, L, Hidalgo, A, Asano, K, Crocker, P R, Storm, G, van Kooyk, Y, den Haan, J M M, Afd Pharmaceutics, Pharmaceutics, Grabowska, J, Affandi, A J, van Dinther, D, Nijen Twilhaar, M K, Olesek, K, Hoogterp, L, Ambrosini, M, Heijnen, D A M, Klaase, L, Hidalgo, A, Asano, K, Crocker, P R, Storm, G, van Kooyk, Y, and den Haan, J M M
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- 2021
16. Liposomes for anti-inflammatory drug delivery in ocular diseases: From in vivo models to clinical application
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Storm, G., Wong, T.T.W., Metselaar, J.M., Wong, Chee Wai, Storm, G., Wong, T.T.W., Metselaar, J.M., and Wong, Chee Wai
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- 2021
17. Requirements for cellular co‐trafficking of factor VIII and von Willebrand factor to Weibel–Palade bodies
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VAN DEN BIGGELAAR, M., BIERINGS, R., STORM, G., VOORBERG, J., and MERTENS, K.
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- 2007
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18. E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cells
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Gholizadeh Soltani, Shima, Visweswaran, Ganesh Ram R, Storm, G, Hennink, Wim E., Kamps, Jan A A M, Kok, Robbert J., Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, Pharmaceutics, and Nanotechnology and Biophysics in Medicine (NANOBIOMED)
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0301 basic medicine ,CANCER-THERAPY ,EXPERIMENTAL ARTHRITIS ,Cell Survival ,media_common.quotation_subject ,Endothelial cells ,Pharmaceutical Science ,02 engineering and technology ,Mice ,03 medical and health sciences ,Drug Delivery Systems ,E-selectin ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,Rapamycin ,Internalization ,LIPID-BILAYERS ,Protein kinase B ,PI3K/AKT/mTOR pathway ,media_common ,Sirolimus ,Dose-Response Relationship, Drug ,biology ,Immunoliposomes ,MTOR ,technology, industry, and agriculture ,ACTIN CYTOSKELETON ,IN-VITRO ,021001 nanoscience & nanotechnology ,Actin cytoskeleton ,Molecular biology ,TNF-ALPHA ,In vitro ,Anti-Bacterial Agents ,PROTEIN-KINASE B ,RHEUMATOID-ARTHRITIS ,030104 developmental biology ,MAMMALIAN TARGET ,Liposomes ,biology.protein ,Cancer research ,Tumor necrosis factor alpha ,Targeted delivery ,E-Selectin ,0210 nano-technology ,medicine.drug - Abstract
Activated endothelial cells play a pivotal role in the pathology of inflammatory disorders and thus present a target for therapeutic intervention by drugs that intervene in inflammatory signaling cascades, such as rapamycin (mammalian target of rapamycin (mTOR) inhibitor). In this study we developed anti-E-selectin immunoliposomes for targeted delivery to E-selectin over-expressing tumor necrosis factor-alpha (TNF-alpha) activated endothelial cells. Liposomes composed of 1,2-dipalmitoyl-sn-glycero-3.; hosphocholine (DPPC), Cholesterol, and 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleimide (DSPE-PEG- Mal) were loaded with rapamycin via lipid film hydration, after which they were further functionalized by coupling N-succinimidyl-S-acetylthioacetate (SATA)-modified mouse anti human E-selectin antibodies to the distal ends of the maleimidyl (Mal)-PEG groups. In cell binding assays, these immunoliposomes bound specifically to TNF-alpha activated endothelial cells. Upon internalization, rapamycin loaded immunoliposomes inhibited proliferation and migration of endothelial cells, as well as expression of inflammatory mediators. Our findings demonstrate that rapamycin-loaded immunoliposomes can specifically inhibit inflammatory responses in inflamed endothelial cells.
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- 2018
19. Report on the Invertebrata of Massachusetts, comprising the Mollusca, Crustacea, Annelida, and Radiata
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Gould, Augustus A. (Augustus Addison), 1805-1866, Storm, G. F., Torbett, Charles W., Massachusetts. Zoological and Botanical Survey, Smithsonian Libraries, Gould, Augustus A. (Augustus Addison), 1805-1866, Storm, G. F., Torbett, Charles W., and Massachusetts. Zoological and Botanical Survey
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Invertebrates ,Massachusetts ,Zoology - Published
- 1841
20. Bioinspired cell-derived nanovesicles protect the heart from ischemia reperfusion injury
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Wang, J, primary, Huang, C.Y, additional, Neupane, Y.R, additional, Wang, X, additional, Zharkova, O, additional, Chong, S.Y, additional, Lee, C.K, additional, Wacker, M.G, additional, Storm, G, additional, and Pastorin, G, additional
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- 2020
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21. Report on the Invertebrata of Massachusetts, comprising the Mollusca, Crustacea, Annelida, and Radiata
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Gould, Augustus A. (Augustus Addison), 1805-1866, Storm, G. F., Torbett, Charles W., Massachusetts. Zoological and Botanical Survey, Smithsonian Libraries and Archives, Gould, Augustus A. (Augustus Addison), 1805-1866, Storm, G. F., Torbett, Charles W., and Massachusetts. Zoological and Botanical Survey
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Invertebrates ,Massachusetts ,Zoology
22. Roost-tree characteristics and abundance of wintering vultures at a communal roost in south central Pennsylvania
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Wright, A L, Yahner, R H, Storm, G L, and BioStor
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- 1986
23. Targeting distinct myeloid cell populations in vivo using polymers, liposomes and microbubbles
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Ergen, Can, Heymann, Felix, Al Rawashdeh, Wa'el, Gremse, Felix, Bartneck, Matthias, Panzer, Ulf, Pola, Robert, Pechar, Michal, Storm, G, Mohr, Nicole, Barz, Matthias, Zentel, Rudolf, Kiessling, Fabian, Trautwein, Christian, Lammers, Twan, Tacke, Frank, Pharmaceutics, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Biomaterials Science and Technology
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0301 basic medicine ,Biodistribution ,Myeloid ,Polymers ,Cell ,Biophysics ,Mice, Nude ,Capsules ,Bioengineering ,Spleen ,02 engineering and technology ,Flow cytometry ,Biomaterials ,Mice ,03 medical and health sciences ,Nanocapsules ,In vivo ,Materials Testing ,medicine ,Animals ,Myeloid Cells ,Tissue Distribution ,Molecular Targeted Therapy ,Microbubbles ,medicine.diagnostic_test ,business.industry ,Macrophages ,021001 nanoscience & nanotechnology ,3. Good health ,Cell biology ,Viscera ,Nanomedicine ,030104 developmental biology ,medicine.anatomical_structure ,Organ Specificity ,Mechanics of Materials ,2023 OA procedure ,Liposomes ,Immunology ,Drug delivery ,Ceramics and Composites ,Targeted delivery ,0210 nano-technology ,business - Abstract
Identifying intended or accidental cellular targets for drug delivery systems is highly relevant for evaluating therapeutic and toxic effects. However, limited knowledge exists on the distribution of nano- and micrometer-sized carrier systems at the cellular level in different organs. We hypothesized that clinically relevant carrier materials, differing in composition and size, are able to target distinct myeloid cell subsets that control inflammatory processes, such as macrophages, neutrophils, monocytes and dendritic cells. Therefore, we analyzed the biodistribution and in vivo cellular uptake of intravenously injected poly(N-(2-hydroxypropyl) methacrylamide) polymers, PEGylated liposomes and poly(butyl cyanoacrylate) microbubbles in mice, using whole-body imaging (computed tomography - fluorescence-mediated tomography), intra-organ imaging (intravital multi-photon microscopy) and cellular analysis (flow cytometry of blood, liver, spleen, lung and kidney). While the three carrier materials shared accumulation in tissue macrophages in liver and spleen, they notably differed in uptake by other myeloid subsets. Kupffer cells and splenic red pulp macrophages rapidly take up microbubbles. Liposomes efficiently reach dendritic cells in liver, lung and kidney. Polymers exhibit the longest circulation half-life and target endothelial cells in the liver, neutrophils and alveolar macrophages. The identification of such previously unrecognized target cell populations might open up new avenues for more efficient drug delivery.
- Published
- 2017
24. A technical protocol for an experimental ex vivo model using arterially perfused porcine eyes
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Rousou, C., Hoogenboom, P., van Overdam, K. A., Storm, G., Dorrestijn, J., Mastrobattista, E., Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, Pharmaceutics, TechMed Centre, and Biomaterials Science and Technology
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Swine ,Enucleation ,In Vitro Techniques ,Eye ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine.artery ,Ophthalmic artery ,medicine ,Extracorporeal model ,Animals ,Protocol (science) ,business.industry ,Retinal Vessels ,Sensory Systems ,Perfusion ,Ophthalmology ,Models, Animal ,030221 ophthalmology & optometry ,Perfused porcine eye model ,Retinal perfusion ,business ,Ex vivo ,Biomedical engineering - Abstract
Ex vivo ocular perfused models have been described in the past and were applied in different mammalian species as platforms to test drug delivery systems and surgical techniques. However, reproduction of those methods is challenging because extensive and precise description of the protocols used is lacking. In this technical paper we provide a detailed description of all the steps to be followed from the enucleation of porcine eyes to cannulation of the ophthalmic artery and perfusion. This model can contribute to the reduction of use of living animals in ophthalmology research, whereas as opposed to in vitro models, it preserves tissue complexity and integrity.
- Published
- 2019
25. Liposomal Drug Delivery in Cancer : Hematological Malignancies and Beyond
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Schiffelers, Raymond, Storm, G, Fens, Marcel, Groen, RWJ, Deshantri, Anil Kumar, Schiffelers, Raymond, Storm, G, Fens, Marcel, Groen, RWJ, and Deshantri, Anil Kumar
- Published
- 2019
26. A technical protocol for an experimental ex vivo model using arterially perfused porcine eyes
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Afd Pharmaceutics, Pharmaceutics, Rousou, C., Hoogenboom, P., van Overdam, K. A., Storm, G., Dorrestijn, J., Mastrobattista, E., Afd Pharmaceutics, Pharmaceutics, Rousou, C., Hoogenboom, P., van Overdam, K. A., Storm, G., Dorrestijn, J., and Mastrobattista, E.
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- 2019
27. Liposomal Drug Delivery in Cancer: Hematological Malignancies and Beyond
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Circulatory Health, CDL Nanomedicine, Schiffelers, Raymond, Storm, G, Fens, Marcel, Groen, RWJ, Deshantri, Anil Kumar, Circulatory Health, CDL Nanomedicine, Schiffelers, Raymond, Storm, G, Fens, Marcel, Groen, RWJ, and Deshantri, Anil Kumar
- Published
- 2019
28. A Local Study of Prevalence of Rabies among Foxes and Striped Skunks
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Verts, B. J. and Storm, G. L.
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- 1966
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29. Effect of Medroxyprogesterone Acetate (Provera) on Productivity in Captive Foxes
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Storm, G. L. and Sanderson, Glen C.
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- 1969
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30. Movements of a Blind Raccoon
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Sunquist, M. E., Montgomery, G. G., and Storm, G. L.
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- 1969
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31. Housing and Reproductive Performance of an Outdoor Colony of Voles
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Storm, G. L. and Sanderson, Glen C.
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- 1968
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32. Ultrasound-mediated drug delivery to the brain: principles, progress and prospects
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Dasgupta, Anshuman, Liu, Mengjiao, Ojha, Tarun, Storm, G, Kiessling, Fabian, Lammers, Twan, Sub Drug targeting, Sub General Pharmaceutics, Pharmaceutics, Sub Drug targeting, Sub General Pharmaceutics, Pharmaceutics, Biomaterials Science and Technology, and Faculty of Science and Technology
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Central nervous system ,Drug delivery to the brain ,02 engineering and technology ,Pharmacology ,Permeability ,Article ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Drug Discovery ,Animals ,Humans ,Medicine ,METIS-320801 ,business.industry ,Drug discovery ,Ultrasound ,Brain ,021001 nanoscience & nanotechnology ,3. Good health ,IR-103530 ,medicine.anatomical_structure ,Ultrasonic Waves ,nervous system ,Drug delivery ,Microbubbles ,cardiovascular system ,Nanomedicine ,Molecular Medicine ,0210 nano-technology ,business ,Sonoporation ,030217 neurology & neurosurgery ,Biotechnology - Abstract
The blood–brain barrier (BBB) limits drug delivery to the central nervous system. When combined with microbubbles, ultrasound can transiently permeate blood vessels in the brain. This approach, which can be referred to as sonoporation or sonopermeabilization, holds significant promise for shuttling large therapeutic molecules, such as antibodies, growth factors and nanomedicine formulations, across the BBB. We here describe the basic principles of BBB permeation using ultrasound and microbubbles, and we summarize several (pre-) clinical studies showing the potential of BBB opening for improving the treatment of cancer and neurodegenerative disorders.
- Published
- 2016
33. Radionuclide imaging of liposomal drug delivery
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van der Geest, Tessa, Laverman, Peter, Metselaar, Josbert M., Storm, G, Boerman, Otto C., Sub General Pharmaceutics, Sub Drug targeting, Pharmaceutics, Biomaterials Science and Technology, Faculty of Science and Technology, Sub General Pharmaceutics, Sub Drug targeting, and Pharmaceutics
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liposomes ,theranostics ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,02 engineering and technology ,Pharmacology ,digestive system ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Pharmacokinetics ,In vivo ,Animals ,Humans ,Medicine ,In patient ,Radionuclide imaging ,Pharmaceutical sciences ,radionuclide imaging ,Radioisotopes ,Tomography, Emission-Computed, Single-Photon ,Liposome ,medicine.diagnostic_test ,business.industry ,METIS-320762 ,021001 nanoscience & nanotechnology ,PET ,Positron emission tomography ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,SPECT ,Drug delivery ,IR-103634 ,Nanomedicine Radboud Institute for Health Sciences [Radboudumc 19] ,0210 nano-technology ,business ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] - Abstract
Expert opinion on drug delivery 13(9), 1231-1242 (2016). doi:10.1080/17425247.2016.1205584, Published by Taylor & Francis Group, Abingdon
- Published
- 2016
34. Intra-articular treatment with triamcinolone acetonide-loaded liposomes in the rat high-fat diet groove model
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Korthagen, N.M., primary, de Visser, H.M., additional, Geusebroek, G., additional, Storm, G., additional, Dupuis, N., additional, Plomp, S.G., additional, Warmink, K., additional, Eijkelkamp, N., additional, Tryfonidou, M., additional, van Weeren, P.R., additional, and Weinans, H., additional
- Published
- 2019
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35. In situ Delivery of Antigen to DC-SIGN + CD14 + Dermal Dendritic Cells Results in Enhanced CD8 + T-Cell Responses
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Fehres, Cynthia M., Van Beelen, Astrid J., Bruijns, Sven C M, Ambrosini, Martino, Kalay, Hakan, Van Bloois, Louis, Unger, Wendy W J, Garcia-Vallejo, Juan J., Storm, G, De Gruijl, Tanja D., Van Kooyk, Yvette V., Pharmaceutics, Sub Atmospheric physics and chemistry, Sub Drug targeting, Molecular cell biology and Immunology, Medical oncology laboratory, CCA - Immuno-pathogenesis, Biomaterials Science and Technology, Faculty of Science and Technology, Pharmaceutics, Sub Atmospheric physics and chemistry, and Sub Drug targeting
- Subjects
CD14 ,Lipopolysaccharide Receptors ,Enzyme-Linked Immunosorbent Assay ,Receptors, Cell Surface ,Dermatology ,CD8-Positive T-Lymphocytes ,Major histocompatibility complex ,Biochemistry ,Sampling Studies ,Antigen ,Cell Movement ,Polysaccharides ,Humans ,Cytotoxic T cell ,Lectins, C-Type ,Molecular Biology ,Cells, Cultured ,Medicine(all) ,Analysis of Variance ,Antigen Presentation ,Toll-like receptor ,integumentary system ,biology ,Dendritic Cells ,Cell Biology ,Dendritic cell ,22/4 OA procedure ,Cell biology ,DC-SIGN ,Liposomes ,Immunology ,biology.protein ,Cell Adhesion Molecules ,CD8 - Abstract
CD14(+) dendritic cells (DCs) present in the dermis of human skin represent a large subset of dermal DCs (dDCs) that are considered macrophage-like cells with poor antigen (cross)-presenting capacity and limited migratory potential to the lymph nodes. CD14(+) dDC highly express DC-specific ICAM-3-grabbing non-integrin (DC-SIGN), a receptor containing potent endocytic capacity, facilitating intracellular routing of antigens to major histocompatibility complex I and II (MHC-I andII) loading compartments for the presentation to antigen-specific CD8(+) and CD4(+) T cells. Here we show using a human skin explant model that the in situ targeting of antigens to DC-SIGN using glycan-modified liposomes enhances the antigen-presenting capacity of CD14(+) dDCs. Intradermal vaccination of liposomes modified with the DC-SIGN-targeting glycan Lewis(X), containing melanoma antigens (MART-1 or Gp100), accumulated in CD14(+) dDCs and resulted in enhanced Gp100- or MART-1-specific CD8(+) T-cell responses. Simultaneous intradermal injection of the cytokines GM-CSF and IL-4 as adjuvant enhanced the migration of the skin DCs and increased the expression of DC-SIGN on the CD14(+) and CD1a(+) dDCs. These data demonstrate that human CD14(+) dDCs exhibit potent cross-presenting capacity when targeted in situ through DC-SIGN.
- Published
- 2015
36. Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy
- Author
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Lobatto, Mark E., Calcagno, Claudia, Otten, Maarten J., Millon, Antoine, Ramachandran, Sarayu, Paridaans, Maarten P M, van der Valk, Fleur M., Storm, G, Stroes, Erik S G, Fayad, Zahi A., Mulder, Willem J M, Metselaar, Josbert M., Pharmaceutics, Sub Drug targeting, Sub General Pharmaceutics, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Radiology and Nuclear Medicine, Other departments, Amsterdam Cardiovascular Sciences, Vascular Medicine, Experimental Vascular Medicine, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Biomaterials Science and Technology, Faculty of Science and Technology, Pharmaceutics, Sub Drug targeting, and Sub General Pharmaceutics
- Subjects
Male ,Chemistry, Pharmaceutical ,[SDV]Life Sciences [q-bio] ,Anti-Inflammatory Agents ,Wistar ,Pharmaceutical Science ,Medicine (miscellaneous) ,use/toxicity ,Pharmacology ,GMP-grade ,Rats, Sprague-Dawley ,General Materials Science ,Clinical imaging ,Pharmaceutical sciences ,Prednisolone/administration & dosage/*analogs & ,Aorta ,Liposome ,Prednisolone phosphate ,Anti-Inflammatory Agents/*administration & dosage/pharmacokinetics/therapeutic ,METIS-315196 ,Pharmaceutical/*methods ,IR-99924 ,3. Good health ,Chemistry ,Nanomedicine ,Aorta/drug effects/pathology ,Molecular Medicine ,Rabbits ,Half-Life ,medicine.drug_class ,Prednisolone ,Biomedical Engineering ,Bioengineering ,Article ,Anti-inflammatory ,derivatives/pharmacokinetics/therapeutic use/toxicity ,Materials Science(all) ,Pharmacokinetics ,medicine ,Humans ,Animals ,Toxicokinetics ,Glucocorticoids/*administration & dosage/pharmacokinetics/therapeutic ,Rats, Wistar ,Glucocorticoids ,business.industry ,Atherosclerosis ,Rats ,Clinical trial ,Formulation design ,Liposomes ,Sprague-Dawley ,Atherosclerosis/*drug therapy/pathology ,business - Abstract
International audience; The present study describes the development of a good manufacturing practice (GMP)-grade liposomal nanotherapy containing prednisolone phosphate for the treatment of inflammatory diseases. After formulation design, GMP production was commenced which yielded consistent, stable liposomes sized 100nm+/-10nm, with a prednisolone phosphate (PLP) incorporation efficiency of 3%-5%. Pharmacokinetics and toxicokinetics of GMP-grade liposomal nanoparticles were evaluated in healthy rats, which were compared to daily and weekly administration of free prednisolone phosphate, revealing a long circulatory half-life with minimal side effects. Subsequently, non-invasive multimodal clinical imaging after liposomal nanotherapy's intravenous administration revealed anti-inflammatory effects on the vessel wall of atherosclerotic rabbits. The present program led to institutional review board approval for two clinical trials with patients with atherosclerosis. FROM THE CLINICAL EDITOR: In drug discovery, bringing production to industrial scale is an essential process. In this article the authors describe the development of an anti-inflammatory nanoparticle according to good manufacturing practice. As a result, this paves the way for translating laboratory studies to clinical trials in humans.
- Published
- 2015
37. Formulation and characterization of microspheres loaded with imatinib for sustained delivery
- Author
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Ramazani, F., Chen, W., Van Nostrum, C. F., Storm, G., Kiessling, F., Lammers, T., Hennink, W. E., Kok, R. J., Sub Drug delivery, Sub General Pharmaceutics, Sub Drug targeting, Pharmaceutics, Biomaterials Science and Technology, Faculty of Science and Technology, Sub Drug delivery, Sub General Pharmaceutics, Sub Drug targeting, and Pharmaceutics
- Subjects
Time Factors ,METIS-315202 ,Pharmaceutical Science ,Matrix (chemical analysis) ,chemistry.chemical_compound ,Differential scanning calorimetry ,Polylactic Acid-Polyglycolic Acid Copolymer ,hemic and lymphatic diseases ,Taverne ,medicine ,Double emulsion (W/O/W) ,Lactic Acid ,Particle Size ,neoplasms ,drug release ,chemistry.chemical_classification ,Drug Carriers ,Chromatography ,Mesylate ,PLGA microspheres ,Imatinib ,Polymer ,log D ,IR-99929 ,Microspheres ,Solvent ,PLGA ,Drug Liberation ,Imatinib mesylate ,chemistry ,Solubility ,Delayed-Action Preparations ,Loading efficiency ,Polyglycolic Acid ,medicine.drug - Abstract
The aim of this study was the development of imatinib-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with high loading efficiency which can afford continuous release of imatinib over a prolonged period of time. Imatinib mesylate loaded PLGA microspheres with a size of 6-20 μm were prepared by a double emulsion (W1/O/W2) method using dichloromethane as volatile solvent. It was found that the microspheres were spherical with a non-porous surface; imatinib loading efficiency (LE) was highly dependent on the pH of the external water phase (W2). By increasing the pH of W2 phase above the highest pKa of imatinib (pKa 8.1), at which imatinib is mainly uncharged, the LE increased from 10% to 90% (pH 5.0 versus pH 9.0). Conversely, only 4% of its counter ion, mesylate, was retained in the microspheres at the same condition (pH 9.0). Since mesylate is highly water soluble, it is unlikely that it partitions into the organic phase. We demonstrated, using differential scanning calorimetry (DSC), that imatinib was molecularly dispersed in the polymeric matrix at loadings up to 8.0%. At higher drug loading, imatinib partially crystallized in the matrix. Imatinib microspheres released their cargo during three months by a combination of diffusion through the polymer matrix and polymer erosion. In conclusion, we have formulated imatinib microspheres with high LE and LC. Although we started with a double emulsion of imatinib mesylate, the obtained microspheres contained imatinib base which was mainly molecularly dispersed in the polymer matrix. These microspheres release imatinib over a 3-month period which is of interest for local treatment of cancer.
- Published
- 2015
38. Intercalating quaternary nicotinamide-based poly(amido amine)s for gene delivery
- Author
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van der Aa, L J, Vader, P, Storm, G, Schiffelers, R M, Engbersen, J F J, Sub General Pharmaceutics, Sub Drug targeting, Pharmaceutics, Sub General Pharmaceutics, Sub Drug targeting, Pharmaceutics, Faculty of Science and Technology, and Biomaterials Science and Technology
- Subjects
Niacinamide ,Erythrocytes ,Quaternary nicotinamide ,Cell Survival ,Polymers ,Stereochemistry ,Green Fluorescent Proteins ,Gene Expression ,Pharmaceutical Science ,Gene delivery ,Transfection ,Hemolysis ,chemistry.chemical_compound ,Genes, Reporter ,Cell Line, Tumor ,Chlorocebus aethiops ,Polymer chemistry ,Intercalation ,Side chain ,Animals ,Humans ,Moiety ,chemistry.chemical_classification ,Nicotinamide ,Gene Transfer Techniques ,Cationic polymerization ,DNA ,Polymer ,Poly(amido amine) ,Intercalating Agents ,Polyplex ,chemistry ,COS Cells ,Nicotinamide cation ,Amine gas treating ,NAD+ kinase ,Plasmids - Abstract
In the development of potent polymeric gene carriers for gene therapy, a good interaction between the polymer and the nucleotide is indispensable to form small and stable polyplexes. Polymers with relatively high cationic charge density are frequently used to provide these interactions, but high cationic charge is usually associated with severe cytotoxicity. In this study an alternative, nucleotide specific binding interaction based on intercalation was investigated to improve polymer/pDNA complex formation. For this purpose bioreducible poly(amido amine) copolymers (p(CBA-ABOL/Nic)) were synthesized with different degrees of intercalating quaternary nicotinamide (Nic) groups and amide-substituted derivatives in their side chains. The quaternary nicotinamide group was chosen as intercalating moiety because this group is part of the naturally occurring NAD+ coenzyme and is therefore expected to be non-toxic and non-carcinogenic. The presence of the quaternary nicotinamide moieties in the poly(amido amine) copolymers showed to effectively promote self-assembled polyplex formation already at low polymer/DNA ratios and results in decreased polyplex size and increased stability of the polyplexes. Furthermore, in contrast to the primary amine functionalized analogs the quaternary nicotinamide polymers showed to be non-hemolytic, indicating their compatibility with cell membranes. Polymers with 25% of Nic in the side chains induced GFP expressions of about 4-5 times that of linear PEI, which is comparable with p(CBA-ABOL), the parent PAA without Nic, but at a two- to fourfold lower required polymer dose. N-phenylation of the nicotinamide functionality even further reduces the required polymer dose to form stable polyplexes, which is a major improvement for these kinds of cationic polymers.
- Published
- 2014
39. Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis
- Author
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Geest, T. van der, Roeleveld, D.M., Walgreen, B., Helsen, M.M.A., Nayak, T.K., Klein, C., Hegen, M., Storm, G., Metselaar, J.M., Berg, W.B. van den, Kraan, P.M. van der, Laverman, P., Boerman, O.C., Koenders, M.I., Geest, T. van der, Roeleveld, D.M., Walgreen, B., Helsen, M.M.A., Nayak, T.K., Klein, C., Hegen, M., Storm, G., Metselaar, J.M., Berg, W.B. van den, Kraan, P.M. van der, Laverman, P., Boerman, O.C., and Koenders, M.I.
- Abstract
Contains fulltext : 191241.pdf (publisher's version ) (Closed access), Objectives: RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled anti-fibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis. Methods: Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores. Results: Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50%, vs 100% in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented. Conclusion: These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.
- Published
- 2018
40. Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes
- Author
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Sadeghi, N, Deckers, Roel, Ozbakir, Burcin, Akthar, Sohail, Kok, Robbert Jan, Lammers, Twan, Storm, G, Sadeghi, N, Deckers, Roel, Ozbakir, Burcin, Akthar, Sohail, Kok, Robbert Jan, Lammers, Twan, and Storm, G
- Published
- 2018
41. Complement activation in vitro and reactogenicity of low-molecular weight dextran-coated SPIONs in the pig CARPA model: Correlation with physicochemical features and clinical information
- Author
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Afd Pharmaceutics, Pharmaceutics, Fülöp, Tamás, Nemes, Reka, Mészáros, Tamás, Urbanics, Rudolf, Kok, Robbert Jan, Jackman, Joshua A., Storm, G, Szebeni, János, Afd Pharmaceutics, Pharmaceutics, Fülöp, Tamás, Nemes, Reka, Mészáros, Tamás, Urbanics, Rudolf, Kok, Robbert Jan, Jackman, Joshua A., Storm, G, and Szebeni, János
- Published
- 2018
42. E-selectin targeted immunoliposomes for rapamycin delivery to activated endothelial cells
- Author
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Afd Pharmaceutics, Pharmaceutics, Gholizadeh Soltani, Shima, Visweswaran, Ganesh Ram R, Storm, G, Hennink, Wim E., Kamps, Jan A A M, Kok, Robbert J., Afd Pharmaceutics, Pharmaceutics, Gholizadeh Soltani, Shima, Visweswaran, Ganesh Ram R, Storm, G, Hennink, Wim E., Kamps, Jan A A M, and Kok, Robbert J.
- Published
- 2018
43. Relationship between polarities of antibiotic and polymer matrix on nanoparticle formulations based on aliphatic polyesters
- Author
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Afd Pharmaceutics, Pharmaceutics, Ritsema, J A S, Herschberg, E M A, Borgos, S E, Løvmo, C, Schmid-Fetzer, R., Te Welscher, Y M, Storm, G, van Nostrum, C F, Afd Pharmaceutics, Pharmaceutics, Ritsema, J A S, Herschberg, E M A, Borgos, S E, Løvmo, C, Schmid-Fetzer, R., Te Welscher, Y M, Storm, G, and van Nostrum, C F
- Published
- 2018
44. Influence of cholesterol inclusion on the doxorubicin release characteristics of lysolipid-based thermosensitive liposomes
- Author
-
Researchgr. Beeldg. Moleculaire Interv., Cancer, Sadeghi, N, Deckers, Roel, Ozbakir, Burcin, Akthar, Sohail, Kok, Robbert Jan, Lammers, Twan, Storm, G, Researchgr. Beeldg. Moleculaire Interv., Cancer, Sadeghi, N, Deckers, Roel, Ozbakir, Burcin, Akthar, Sohail, Kok, Robbert Jan, Lammers, Twan, and Storm, G
- Published
- 2018
45. 342 BONE DENSITY IN STRENGTH TRAINED PRE-MENOPAUSAL FEMALES
- Author
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Hess, S. B., Keller, D. A., Thomas, P. D., and Storm, G. A.
- Published
- 1994
46. Lipogels responsive to near-infrared light for the triggered release of therapeutic agents
- Author
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Martín-Saavedra, Francisco, Ruiz-Hernández, Eduardo, Escudero-Duch, Clara, Prieto, Martín, Arruebo, Manuel, Sadeghi, Negar, Deckers, Roel, Storm, G, Hennink, Wim E., Santamaría, Jesús, Vilaboa, Nuria, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics
- Subjects
Materials science ,Thermosensitive liposome ,Infrared Rays ,Near infrared ,Biomedical Engineering ,Nanoparticle ,Metal Nanoparticles ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Nanomaterials ,Biomaterials ,Drug Delivery Systems ,Animals ,In situ polymerization ,Molecular Biology ,Liposome ,Fibrin ,Temperature ,technology, industry, and agriculture ,Hydrogels ,General Medicine ,021001 nanoscience & nanotechnology ,Controlled release ,0104 chemical sciences ,Drug Liberation ,Hydrogel ,Doxorubicin ,Drug delivery ,Self-healing hydrogels ,Liposomes ,Doxorubicin Hydrochloride ,Cattle ,Gold ,0210 nano-technology ,Gels ,Biomedical engineering ,Optical hyperthermia ,Photoabsorber ,Biotechnology - Abstract
Here we report a composite system based on fibrin hydrogels that incorporate in their structure near-infrared (NIR) responsive nanomaterials and thermosensitive liposomes (TSL). Polymerized fibrin networks entrap simultaneously gold-based nanoparticles (NPs) capable of transducing NIR photon energy into heat, and lysolipid-incorporated TSL (LTSL) loaded with doxorubicin hydrochloride (DOX). NIR irradiation of the resulting hydrogels (referred to as “lipogels”) with 808 nm laser light increased the temperature of the illuminated areas, leading to the release of the liposomal cargo. Levels of DOX that release from the “smart” composites were dependent on the concentration of NIR nanotransducers loaded in the lipogel, the intensity of the electromagnetic energy deposited and the irradiation regime. Released DOX retained its bioactivity, as shown in cultures of epithelial carcinoma cells. Finally, the developed drug delivery platform was refined by using NIR-photoabsorbers based on copper sulfide NPs to generate completely biodegradable composites as well as through the incorporation of cholesterol (Ch) in LTSL formulation, which lessens leakiness of the liposomal cargo at physiological temperature. This remotely controlled system may suit well for those therapies that require precise control over the dose of delivered drug in a defined spatiotemporal framework. Statement of Significance Hydrogels composed of fibrin embedding nanoparticles responsive to near infrared (NIR) energy and thermosensitive liposomes loaded with doxorubicin hydrochloride (DOX), were prepared by in situ polymerization. NIR-light irradiation of these constructs, referred to as “NIR responsive lipogels”, results in the controlled release of DOX to the surrounding medium. This technology may use fully degradable components and can preserve the bioactivity of liposomal cargo after remote triggering to finely regulate the dose and bioavailability of delivered payloads. NIR responsive lipogels technology overcomes the limitations of drug release systems based on the combination of liposomes and degradable polymeric materials, which in many cases lead to insufficient release at therapy onset or to overdose during high degradation period.
- Published
- 2017
47. Nanomedicine Strategies to Target Tumor-Associated Macrophages
- Author
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Binnemars-Postma, Karin A., Storm, G, Prakash, Jai, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics
- Subjects
0301 basic medicine ,active targeting ,Cell type ,Review ,Catalysis ,Metastasis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,Downregulation and upregulation ,stomatognathic system ,Neoplasms ,Animals ,Humans ,Medicine ,cancer ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,Tumor microenvironment ,business.industry ,tumor-associated macrophages ,Organic Chemistry ,Cancer ,General Medicine ,Macrophage Activation ,medicine.disease ,M2 Macrophage ,passive targeting ,Computer Science Applications ,macrophages ,Nanomedicine ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Immunology ,Cancer research ,nanoparticles ,business ,Function (biology) - Abstract
In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.
- Published
- 2017
48. Nanopolymersomes with an Ultrahigh Iodine Content for High-Performance X-Ray Computed Tomography Imaging In Vivo
- Author
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Zou, Yan, Wei, Yaohua, Wang, Guanglin, Meng, Fenghua, Gao, Mingyuan, Storm, G, Zhong, Zhiyuan, Pharmaceutics, and Afd Pharmaceutics
- Subjects
medicine.medical_specialty ,Materials science ,Blood pool ,Iohexol ,chemistry.chemical_element ,Contrast Media ,02 engineering and technology ,010402 general chemistry ,Iodine ,01 natural sciences ,Mice ,Materials Science(all) ,X ray computed ,In vivo ,medicine ,Animals ,General Materials Science ,Medical physics ,contrast agents ,targeted imaging ,Mechanical Engineering ,computed tomography ,Iodides ,021001 nanoscience & nanotechnology ,Biocompatible material ,0104 chemical sciences ,Nanostructures ,chemistry ,Mechanics of Materials ,polymersomes ,2023 OA procedure ,Tomography ,0210 nano-technology ,Tomography, X-Ray Computed ,Preclinical imaging ,Biomedical engineering ,medicine.drug - Abstract
Biodegradable nanopolymersomes with an ultrahigh iodine content for high-performance CT imaging in vivo were designed. To obtain iodine-rich nanopolymersomes, we devised and prepared a new iodine-functionalized trimethylene carbonate (IC) monomer in two straight steps with an overall yield of 25% by the Finkelstein reaction. Gel permeation chromatography displayed a unimodal distribution with a moderate Mw/Mn of 1.40, confirming successful synthesis of PEG-b-PIC. Interestingly, PEG-b-PIC had an ultrahigh iodine content of 60.4 wt%, which is significantly higher than iohexol and all reported iodinated nanoparticle platforms. Remarkably, the PEG-b-PIC diblock copolymer was readily self-assembled into stable nanopolymersomes. Dynamic light scattering (DLS) showed a small hydrodynamic size of =100 nm with a low polydispersity index =0.10. Transmission electron microscopy (TEM) image confirmed their small size and vesicle structure, likely due to their thick membrane and the inherent PEG stealth ability. The stability of iodine conjugated with an aliphatic chain is usually weaker than that conjugated with aromatic derivatives. However, unlike traditional small molecules, all iodine atoms in IPs are sequestered in the hydrophobic membrane of polymersomes, which would effectively protect iodine from leakage. The in vivo SPECT/CT images showed that in sharp contrast to fast accumulation of Na125I in the thyroid and bladder, I-labeled IPs had a long circulation time and predominantly accumulated in the RES like spleen and liver, further corroborating that IPs are stable in circulation and iodine leakage is negligible.
- Published
- 2017
49. Liposomal treatment of experimental arthritis can be monitored noninvasively with a radiolabeled anti-fibroblast activation protein antibody
- Author
-
Van Der Geest, Tessa, Laverman, Peter, Gerrits, Danny, Walgreen, Birgitte, Helsen, Monique, Klein, Christian, Nayak, Tapan K., Storm, G, Metselaar, Josbert M., Koenders, Marije I., Boerman, Otto C., Pharmaceutics, Afd Pharmaceutics, Biomaterials Science and Technology, Pharmaceutics, and Afd Pharmaceutics
- Subjects
Male ,Pathology ,Arthritis ,Technetium ,Arthritis, Rheumatoid ,Mice ,0302 clinical medicine ,Fibroblast activation protein, alpha ,Liposome ,biology ,Serine Endopeptidases ,Antibodies, Monoclonal ,Molecular Imaging ,Treatment Outcome ,Prednisolone Phosphate-Encapsulating Peg Liposomes ,Gelatinases ,Mice, Inbred DBA ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Isotope Labeling ,Collagen-Induced Arthritis ,Prednisolone ,Nanomedicine Radboud Institute for Health Sciences [Radboudumc 19] ,medicine.symptom ,Antibody ,Drug Monitoring ,Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5] ,medicine.drug ,medicine.medical_specialty ,Single Photon Emission Computed Tomography Computed Tomography ,chemistry.chemical_element ,Inflammation ,03 medical and health sciences ,Therapy Monitoring ,Endopeptidases ,medicine ,Animals ,Radiology, Nuclear Medicine and imaging ,Glucocorticoids ,Spect/Ct Imaging ,030203 arthritis & rheumatology ,Fibroblast Activation Protein ,business.industry ,Membrane Proteins ,medicine.disease ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,chemistry ,Delayed-Action Preparations ,Liposomes ,2023 OA procedure ,biology.protein ,Radiopharmaceuticals ,business ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] - Abstract
Item does not contain fulltext Rheumatoid arthritis is a chronic autoimmune disorder resulting in synovial inflammation. Fibroblast activation protein (FAP) is overexpressed by fibroblastlike synoviocytes in arthritic joints. Radioimmunoimaging with an anti-FAP antibody might be used to monitor the response to therapy, thus enabling tailored therapy strategies and therapeutic outcomes. The aim of this study was to assess whether a radiolabeled anti-FAP antibody could be used to monitor the efficacy of treatment with long-circulating liposomes (LCL) containing prednisolone phosphate (PLP-LCL) in a mouse model of arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in male DBA/1J mice. Mice were treated with a single injection (10 mg/kg) of PLP-LCL or empty LCL as a control. SPECT and CT images were acquired 24 h after injection of 99mTc-labeled succinimidyl-hydrazinonicotinamide (99mTc-S-HYNIC)-conjugated anti-FAP antibody 28H1 at 2, 5, and 9 d after treatment. The uptake of 99mTc-S-HYNIC-28H1 in all joints was quantified and correlated with macroscopic arthritis scores. RESULTS: Treatment of CIA with PLP-LCL significantly suppressed joint swelling. At just 1 d after treatment, the macroscopic arthritis scores had decreased by 50%. Scores decreased further, to only 10% of the initial scores, at 5 and 9 d after treatment. In contrast, macroscopic arthritis scores had increased up to 600% in untreated mice at 9 d after the injection of empty LCL. 99mTc-S-HYNIC-28H1 uptake ranged from 1.5 percentage injected dose per gram in noninflamed joints to 22.6 percentage injected dose per gram in severely inflamed joints. The uptake of radiolabeled 28H1 in inflamed joints (percentage injected dose) correlated with the arthritis score (Spearman rho, 0.77; P < 0.0001). Moreover, the uptake of 99mTc-S-HYNIC-28H1 was slightly increased at 9 d after therapy but was not seen macroscopically, indicating that SPECT/CT imaging might be more sensitive than the macroscopic arthritis scoring method. CONCLUSION: SPECT/CT imaging with 99mTc-S-HYNIC-28H1 specifically monitored the response to therapy, and tracer accumulation correlated with the severity of inflammation. In addition, SPECT/CT imaging was potentially more sensitive than the macroscopic arthritis scoring method. This study showed that SPECT/CT with 99mTc-S-HYNIC-28H1 could be used to noninvasively monitor the course of CIA in mice.
- Published
- 2017
50. Liposomal corticosteroids for the treatment of inflammatory disorders and cancer
- Author
-
Ozbakir, Burcin, Crielaard, Bart J, Metselaar, Josbert M, Storm, G, Lammers, Twan, Sub Drug targeting, Sub General Pharmaceutics, Pharmaceutics, Sub Drug targeting, Sub General Pharmaceutics, Pharmaceutics, Biomaterials Science and Technology, and Faculty of Science and Technology
- Subjects
Biodistribution ,Multiple Sclerosis ,Anti-Inflammatory Agents ,Pharmaceutical Science ,Inflammation ,Pharmacology ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatoid ,Neoplasms ,medicine ,Humans ,Glucocorticoids ,030304 developmental biology ,0303 health sciences ,Liposome ,METIS-309153 ,business.industry ,Multiple sclerosis ,Arthritis ,Cancer ,medicine.disease ,Asthma ,3. Good health ,IR-95131 ,Rheumatoid arthritis ,Toxicity ,Drug delivery ,Liposomes ,Nanoparticles ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Glucocorticoids (GC) are known for their potent immunosuppressive and anti-inflammatory properties. As a consequence, they have been extensively used for the treatment of many different diseases. Prolonged and/or high-dose GC therapy, however, generally comes with severe side effects, resulting not only from their very diverse mechanism(s) of action, but also from their relatively poor biodistribution. Drug delivery systems, and in particular liposomes, have been extensively used to enhance the biodistribution and the target site accumulation of GC, and to thereby improve the balance between their efficacy and their toxicity. Many different types of liposomes have been employed, and both local and systemic treatments have been evaluated. We here summarize the progress made in the use of liposomal GC formulations for the treatment of asthma, rheumatoid arthritis, multiple sclerosis and cancer, and we show that the targeted delivery of GC to pathological sites holds significant clinical potential.
- Published
- 2014
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