{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:51:55Z","timestamp":1790297515041,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008730","name":"Norwegian Cancer Society","doi-asserted-by":"publisher","award":["197837"],"award-info":[{"award-number":["197837"]}],"id":[{"id":"10.13039\/100008730","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SINTEF","award":["197837"],"award-info":[{"award-number":["197837"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 \u00b5m microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/md20120744","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T06:04:36Z","timestamp":1669615476000},"page":"744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Alginate Microsphere Encapsulation of Drug-Loaded Nanoparticles: A Novel Strategy for Intraperitoneal Drug Delivery"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0697-9750","authenticated-orcid":false,"given":"Karianne Giller","family":"Fleten","sequence":"first","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway"},{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Hyldbakk","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway"},{"name":"Department of Physics, Norwegian University of Science and Technology (NTNU), 7034 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Einen","sequence":"additional","affiliation":[{"name":"Department of Physics, Norwegian University of Science and Technology (NTNU), 7034 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sopisa","family":"Benjakul","sequence":"additional","affiliation":[{"name":"Department of Physics, Norwegian University of Science and Technology (NTNU), 7034 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berit L\u00f8kensgard","family":"Strand","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), 7034 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina de Lange","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Physics, Norwegian University of Science and Technology (NTNU), 7034 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-7276","authenticated-orcid":false,"given":"\u00ddrr","family":"M\u00f8rch","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Nanomedicine, SINTEF Industry, 7034 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-0780","authenticated-orcid":false,"given":"Kjersti","family":"Flatmark","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway"},{"name":"Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway"},{"name":"Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2016015798","article-title":"Overview on Therapeutic Applications of Microparticulate Drug Delivery Systems","volume":"33","author":"Bale","year":"2016","journal-title":"Crit. Rev. Ther. Drug Carr. Syst."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lengyel, M., K\u00e1llai-Szab\u00f3, N., Antal, V., Laki, A.J., and Antal, I. (2019). Microparticles, Microspheres, and Microcapsules for Advanced Drug Delivery. Sci. Pharm., 87.","DOI":"10.3390\/scipharm87030020"},{"key":"ref_3","first-page":"8886095","article-title":"Current Status of Alginate in Drug Delivery","volume":"2020","author":"Hariyadi","year":"2020","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.progpolymsci.2011.06.003","article-title":"Alginate: Properties and Biomedical Applications","volume":"37","author":"Lee","year":"2012","journal-title":"Prog. Polym. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ijpharm.2013.09.035","article-title":"Mucoadhesive Hybrid Gel Improves Intraperitoneal Platinum Delivery","volume":"458","author":"Cho","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"119689","DOI":"10.1016\/j.carbpol.2022.119689","article-title":"Sodium Alginate Based Drug Delivery in Management of Breast Cancer","volume":"292","author":"Shaikh","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s00125-013-2906-0","article-title":"Sustained Function of Alginate-Encapsulated Human Islet Cell Implants in the Peritoneal Cavity of Mice Leading to a Pilot Study in a Type 1 Diabetic Patient","volume":"56","author":"Chintinne","year":"2013","journal-title":"Diabetologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/S1470-2045(16)30500-9","article-title":"Prognosis of Patients with Peritoneal Metastatic Colorectal Cancer given Systemic Therapy: An Analysis of Individual Patient Data from Prospective Randomised Trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) Database","volume":"17","author":"Franko","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1080\/02656736.2017.1310938","article-title":"Pseudomyxoma Peritonei: Natural History and Treatment","volume":"33","author":"Mittal","year":"2017","journal-title":"Int. J. Hyperth."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.ejso.2012.06.552","article-title":"Evaluation of Complete Cytoreductive Surgery and Two Intraperitoneal Chemotherapy Techniques in Pseudomyxoma Peritonei","volume":"38","author":"Flatmark","year":"2012","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.jamcollsurg.2013.12.013","article-title":"Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Experience with 1000 Patients","volume":"218","author":"Levine","year":"2014","journal-title":"J. Am. Coll. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/ags3.12060","article-title":"Treatment of Patients with Peritoneal Metastases from Gastric Cancer","volume":"2","author":"Kitayama","year":"2018","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.addr.2016.07.001","article-title":"Nanomedicine-Based Intraperitoneal Therapy for the Treatment of Peritoneal Carcinomatosis\u2014Mission Possible?","volume":"108","author":"Dakwar","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hyldbakk, A., Fleten, K.G., Snipstad, S., \u00c5slund, A.K.O., Davies, C.D.L., Flatmark, K., and M\u00f8rch, \u00dd.A. (2022). Intraperitoneal Administration of Cabazitaxel-Loaded Nanoparticles in Peritoneal Metastasis Models, Manuscript submitted for publication.","DOI":"10.1016\/j.nano.2023.102656"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.2147\/DDDT.S64940","article-title":"Preclinical Profile of Cabazitaxel","volume":"8","author":"Vrignaud","year":"2014","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104707","DOI":"10.1016\/j.chemphyslip.2018.11.009","article-title":"Cabazitaxel and Thymoquinone Co-Loaded Lipospheres as a Synergistic Combination for Breast Cancer","volume":"224","author":"Kommineni","year":"2019","journal-title":"Chem. Phys. Lipids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.biopha.2018.11.145","article-title":"Cabazitaxel and Silibinin Co-Encapsulated Cationic Liposomes for CD44 Targeted Delivery: A New Insight into Nanomedicine Based Combinational Chemotherapy for Prostate Cancer","volume":"110","author":"Mahira","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jconrel.2018.11.029","article-title":"Cabazitaxel-Loaded Poly(2-Ethylbutyl Cyanoacrylate) Nanoparticles Improve Treatment Efficacy in a Patient Derived Breast Cancer Xenograft","volume":"293","author":"Fusser","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.ultrasmedbio.2020.12.026","article-title":"Sonopermeation Enhances Uptake and Therapeutic Effect of Free and Encapsulated Cabazitaxel","volume":"47","author":"Snipstad","year":"2021","journal-title":"Ultrasound Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1016\/j.ultrasmedbio.2017.06.029","article-title":"Ultrasound Improves the Delivery and Therapeutic Effect of Nanoparticle-Stabilized Microbubbles in Breast Cancer Xenografts","volume":"43","author":"Snipstad","year":"2017","journal-title":"Ultrasound Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s11095-009-0031-z","article-title":"Drug Delivery Systems for Intraperitoneal Therapy","volume":"27","author":"Bajaj","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"720858","DOI":"10.1155\/2013\/720858","article-title":"Optimization of Drug Delivery Systems for Intraperitoneal Therapy to Extend the Residence Time of the Chemotherapeutic Agent","volume":"2013","author":"Ceelen","year":"2013","journal-title":"Sci. World J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/bit.260260111","article-title":"Diffusion Characteristics of Substrates in Ca-Alginate Gel Beads","volume":"26","author":"Tanaka","year":"1984","journal-title":"Biotechnol. Bioeng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/10611860701603372","article-title":"Design Aspects of Poly(Alkylcyanoacrylate) Nanoparticles for Drug Delivery","volume":"15","author":"Vauthier","year":"2007","journal-title":"J. Drug Target."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1002\/jbm.a.37255","article-title":"Alginate Hydrogels Functionalized with \u03b2-Cyclodextrin as a Local Paclitaxel Delivery System","volume":"109","author":"Omtvedt","year":"2021","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"78208","DOI":"10.18632\/oncotarget.20596","article-title":"Nanoparticle as a Novel Tool in Hyperthermic Intraperitoneal and Pressurized Intraperitoneal Aerosol Chemotheprapy to Treat Patients with Peritoneal Carcinomatosis","volume":"8","author":"Nowacki","year":"2017","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wouters, R., Westr\u00f8m, S., Vankerckhoven, A., Thirion, G., Ceusters, J., Claes, S., Schols, D., B\u00f8nsdorff, T.B., Vergote, I., and Coosemans, A. (2022). Effect of Particle Carriers for Intraperitoneal Drug Delivery on the Course of Ovarian Cancer and Its Immune Microenvironment in a Mouse Model. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040687"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/S0140-6736(94)90067-1","article-title":"Insulin Independence in a Type 1 Diabetic Patient after Encapsulated Islet Transplantation","volume":"343","author":"Heintz","year":"1994","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jhep.2019.12.002","article-title":"Alginate Microencapsulated Human Hepatocytes for the Treatment of Acute Liver Failure in Children","volume":"72","author":"Dhawan","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kommineni, N., Mahira, S., Domb, A.J., and Khan, W. (2019). Cabazitaxel-Loaded Nanocarriers for Cancer Therapy with Reduced Side Effects. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030141"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tian, Z., Yang, Y., Yang, Y., Zhang, F., Li, P., Wang, J., Yang, J., Zhang, P., Yao, W., and Wang, X. (2020). High Cumulative Doxorubicin Dose for Advanced Soft Tissue Sarcoma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07663-x"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1102\/1470-7330.2001.002","article-title":"Detection of Peritoneal Metastases","volume":"1","author":"Healy","year":"2001","journal-title":"Cancer Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00276-008-0456-9","article-title":"Peritoneal Surface Area: Measurements of 40 Structures Covered by Peritoneum: Correlation between Total Peritoneal Surface Area and the Surface Calculated by Formulas","volume":"31","author":"Albanese","year":"2009","journal-title":"Surg. Radiol. Anat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/cmmi.1639","article-title":"Nanoparticle-Stabilized Microbubbles for Multimodal Imaging and Drug Delivery","volume":"10","author":"Hansen","year":"2015","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"\u00c5slund, A.K.O., Vandebriel, R.J., Caputo, F., de Jong, W.H., Delmaar, C., Hyldbakk, A., Rustique, E., Schmid, R., Snipstad, S., and Texier, I. (2022). A Comparative Biodistribution Study of Polymeric and Lipid-Based Nanoparticles. Drug Deliv. Transl. Res., 1\u201318.","DOI":"10.1007\/s13346-022-01157-y"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11876","DOI":"10.1039\/c2ra21544f","article-title":"Highly Lipophilic Fluorescent Dyes in Nano-Emulsions: Towards Bright Non-Leaking Nano-Droplets","volume":"2","author":"Klymchenko","year":"2012","journal-title":"RSC Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1080\/02652040210144243","article-title":"Alginate-Polylysine-Alginate Microcapsules: Effect of Size Reduction on Capsule Properties","volume":"19","author":"Strand","year":"2002","journal-title":"J. Microencapsul."},{"key":"ref_38","unstructured":"(2022, September 19). ImageJ2: ImageJ for the next Generation of Scientific Image Data|BMC Bioinformatics|Full Text. Available online: https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-017-1934-z."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jcis.2009.05.027","article-title":"Prediction Models for Shape and Size of Ca-Alginate Macrobeads Produced through Extrusion\u2013Dripping Method","volume":"338","author":"Chan","year":"2009","journal-title":"J. Colloid Interface Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sert, N.P.D., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., Dirnagl, U., and Emerson, M. (2020). Reporting Animal Research: Explanation and Elaboration for the ARRIVE Guidelines 2.0. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000411"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/ame2.12015","article-title":"Environmental Enrichment and Mouse Models: Current Perspectives","volume":"1","author":"Bayne","year":"2018","journal-title":"Anim. Model Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.humpath.2009.12.013","article-title":"Exploring the Peritoneal Surface Malignancy Phenotype\u2014A Pilot Immunohistochemical Study of Human Pseudomyxoma Peritonei and Derived Animal Models","volume":"41","author":"Flatmark","year":"2010","journal-title":"Hum. Pathol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/12\/744\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:27:36Z","timestamp":1760146056000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/12\/744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,26]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["md20120744"],"URL":"https:\/\/doi.org\/10.3390\/md20120744","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,26]]}}}