{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T07:58:25Z","timestamp":1778313505555,"version":"3.51.4"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Research Centre Egypt"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bioprocess Biosyst Eng"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Digenea simplex<\/jats:italic> (<jats:italic>D. simplex<\/jats:italic>), an Egyptian marine red macroalga, contains a diverse group of phytochemicals with unique bioactivities. At the same time, the synthesis of nanosuspension (NS) has received increasing interest to optimize the technological aspects of drugs. Thence, the main objective of this work was to use the chloroform extract (ChlE) of <jats:italic>D. simplex<\/jats:italic> to prepare its nanosuspension (ChlE-NS) formulation to increase its aqueous solubility, thereby improving its bioactivity.\u00a0By using FTIR, GC\/MS analysis, and phytochemical screening assays, the chemical profiling of ChlE was assessed. NS was prepared by the antisolvent precipitation technique using 1.5% w\/v polyvinyl alcohol (PVA). A light microscope, FTIR, particle size distribution, polydispersity index (PDI), and zeta potential (ZP) measurements was used to characterize the prepared NS. Four cancer cell lines were used in the MTT experiment to investigate the anticancer potential of ChlE and ChlE-NS. An apoptotic mechanism was established using acridine orange\/ethidium bromide (AO\/EB) dual staining, DNA fragmentation, and increased caspase activity. ChlE and ChlE-NS were also evaluated as antioxidants using DPPH and ABTS free radical assays. The results showed that, when compared to ChlE, ChlE-NS had greater cytotoxic activity against the four cancer cell lines. However, results of antioxidant activity showed that ChlE-NS had an IC<jats:sub>50<\/jats:sub> of 36.86\u2009\u00b1\u20090.09 and 63.5\u2009\u00b1\u20090.47%, while ChlE had values of 39.90\u2009\u00b1\u20090.08 and 86.5\u2009\u00b1\u20090.8% in DPPH and ABTS assays, respectively. Based on the results of this research, <jats:italic>D. simplex<\/jats:italic> ChlE-NS may be an effective strategy for enhancing ChlE's cytotoxic and antioxidant activities.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00449-022-02833-6","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T02:02:30Z","timestamp":1671501750000},"page":"279-296","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Enhancement of cytotoxic and antioxidant activities of Digenea simplex chloroform extract using the nanosuspension technique"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1230-0601","authenticated-orcid":false,"given":"Hanaa M.","family":"El-Rafie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enas A.","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7280-0734","authenticated-orcid":false,"given":"Magdy K.","family":"Zahran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"2833_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s43094-022-00400-0","volume":"8","author":"ZM Mazayen","year":"2022","unstructured":"Mazayen ZM, Ghoneim AM, Elbatanony RS, Basalious EB, Bendas ER (2022) Pharmaceutical nanotechnology: from the bench to the market. Futur J Pharm Sci 8:12. https:\/\/doi.org\/10.1186\/s43094-022-00400-0","journal-title":"Futur J Pharm Sci"},{"key":"2833_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.888177","volume":"10","author":"T Ali","year":"2022","unstructured":"Ali T, Hussain F, Naeem M, Khan A, Al-Harrasi A (2022) Nanotechnology approach for exploring the enhanced bioactivities and biochemical characterization of freshly prepared Nigella sativa L. nanosuspensions and their phytochemical profile. Front Bioeng Biotechnol 10:888177. https:\/\/doi.org\/10.3389\/fbioe.2022.888177","journal-title":"Front Bioeng Biotechnol"},{"key":"2833_CR3","first-page":"59","volume":"4","author":"SS Pawar","year":"2017","unstructured":"Pawar SS, Dahifale BR, Nagargoje SP, Shendge RS (2017) Nanosuspension technologies for delivery of drugs. Nanosci Nanotech Res 4:59\u201366","journal-title":"Nanosci Nanotech Res"},{"key":"2833_CR4","doi-asserted-by":"publisher","first-page":"164","DOI":"10.4103\/2221-1691.280293","volume":"10","author":"F Zafar","year":"2020","unstructured":"Zafar F, Jahan N, Rahman KU, Asi MR, Zafar WUI (2020) Nanosuspension enhances dissolution rate and oral bioavailability of Terminalia arjuna bark extract in vivo and in vitro. Asian Pac J Trop Biomed 10:164\u2013171","journal-title":"Asian Pac J Trop Biomed"},{"key":"2833_CR5","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.12980\/APJTB.4.2014C980","volume":"4","author":"T Gunasekaran","year":"2014","unstructured":"Gunasekaran T, Haile T, Nigusse T, Dhanaraju MD (2014) Nanotechnology: an effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pac J Trop Biomed 4:S1\u2013S7. https:\/\/doi.org\/10.12980\/APJTB.4.2014C980","journal-title":"Asian Pac J Trop Biomed"},{"key":"2833_CR6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.22377\/ajp.v12i02.2323","volume":"12","author":"SR Pathak","year":"2018","unstructured":"Pathak SR, Kumar R, Mehndiratta P, Mishra NK, Thukral A, Singh R (2018) Bioavailability enhancement of poorly water-soluble nano diosgenin by encapsulation using chitosan\/bovine serum albumin bilayers. Asian J Pharm 12:115\u2013119. https:\/\/doi.org\/10.22377\/ajp.v12i02.2323","journal-title":"Asian J Pharm"},{"key":"2833_CR7","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1021\/acsabm.9b00843","volume":"3","author":"L Zhao","year":"2020","unstructured":"Zhao L, Xing Y, Wang R, Yu F, Yu F (2020) Self-assembled nanomaterials for enhanced phototherapy of cancer. ACS Appl Bio Mater 3:86\u2013106. https:\/\/doi.org\/10.1021\/acsabm.9b00843","journal-title":"ACS Appl Bio Mater"},{"key":"2833_CR8","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40824-020-0184-8","volume":"5","author":"S Jacob","year":"2020","unstructured":"Jacob S, Nair AB, Shah J (2020) Emerging role of nanosuspensions in drug delivery systems. Biomater Res 5:24. https:\/\/doi.org\/10.1186\/s40824-020-0184-8","journal-title":"Biomater Res"},{"key":"2833_CR9","doi-asserted-by":"publisher","first-page":"10485","DOI":"10.26717\/bjstr.2019.14.002511","volume":"14","author":"RW Kihagi","year":"2019","unstructured":"Kihagi RW, Amuka O, Machocho AK, Wafula AW (2019) Phytomedicine and allied compounds in both human and animal healthcare. BJSTR 14:10485\u201310491. https:\/\/doi.org\/10.26717\/bjstr.2019.14.002511","journal-title":"BJSTR"},{"issue":"1","key":"2833_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5580\/2c1f","volume":"12","author":"I Mohamed","year":"2012","unstructured":"Mohamed I, Shuid A, Borhanuddin B, Fozi N (2012) The Application of phytomedicine in modern drug development. Internet J Herb Plant Med 12(1):1\u20139. https:\/\/doi.org\/10.5580\/2c1f","journal-title":"Internet J Herb Plant Med"},{"key":"2833_CR11","first-page":"27","volume":"4","author":"A Karimi","year":"2015","unstructured":"Karimi A, Majlesi M, Rafieian-Kopaei M (2015) Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 4:27\u201330","journal-title":"J Nephropharmacol"},{"key":"2833_CR12","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.7314\/APJCP.2013.14.4.2213","volume":"14","author":"S Muthuirulappan","year":"2013","unstructured":"Muthuirulappan S, Francis SP (2013) Anti-cancer mechanism and possibility of nano-suspension formulation for a marine algae product fucoxanthin. Asian Pacific J Cancer Prev 14:2213\u20132216. https:\/\/doi.org\/10.7314\/APJCP.2013.14.4.2213","journal-title":"Asian Pacific J Cancer Prev"},{"key":"2833_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fmars.2020.614766","volume":"7","author":"DL Dayanidhi","year":"2021","unstructured":"Dayanidhi DL, Thomas BC, Osterberg JS, Vuong M, Vargas G, Kwartler SK, Schmaltz E, Dunphy-Daly MM, Schultz TF, Rittschof D, Eward Roy C, Somarelli JA (2021) Exploring the diversity of the marine environment for new anti-cancer compounds. Front Mar Sci 7:614766. https:\/\/doi.org\/10.3389\/fmars.2020.614766","journal-title":"Front Mar Sci"},{"key":"2833_CR14","doi-asserted-by":"publisher","first-page":"83","DOI":"10.4103\/0975-7406.171700","volume":"8","author":"H Malve","year":"2016","unstructured":"Malve H (2016) Exploring the ocean for new drug developments: marine pharmacology. J Pharm Bioallied Sci 8:83\u201391. https:\/\/doi.org\/10.4103\/0975-7406.171700","journal-title":"J Pharm Bioallied Sci"},{"key":"2833_CR15","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s43141-021-00290-4","volume":"26","author":"A Karthikeyan","year":"2022","unstructured":"Karthikeyan A, Joseph A, Nair BG (2022) Promising bioactive compounds from the marine environment and their potential effects on various diseases. J Genet Eng Biotechnol 26:14. https:\/\/doi.org\/10.1186\/s43141-021-00290-4","journal-title":"J Genet Eng Biotechnol"},{"key":"2833_CR16","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s11160-021-09669-5","volume":"32","author":"KL Nash","year":"2022","unstructured":"Nash KL, van Putten I, Alexander KA, Bettiol S, Cvitanovic C, Farmery AK, Flies EJ, Ison S, Kelly R, Mackay M, Murray L, Norris K, Robinson LM, Scott J, Ward D, Vince J (2022) Oceans and society: feedbacks between ocean and human health. Rev Fish Biol Fish 32:161\u2013187. https:\/\/doi.org\/10.1007\/s11160-021-09669-5","journal-title":"Rev Fish Biol Fish"},{"key":"2833_CR17","doi-asserted-by":"publisher","first-page":"232","DOI":"10.22270\/jddt.v10i5.4422","volume":"10","author":"V Dias","year":"2020","unstructured":"Dias V, Bandeira S, Cha\u00faque E, Lipassula M, Mussagy A (2020) Evaluation of phytocompounds and chemical elements present in selected species of seaweeds, to sustain future quantitative analysis for bioactive compounds. J Drug Deliv Ther 10:232\u2013239","journal-title":"J Drug Deliv Ther"},{"key":"2833_CR18","doi-asserted-by":"publisher","first-page":"97","DOI":"10.11648\/j.ajac.20210904.11","volume":"9","author":"MT Hanani","year":"2021","unstructured":"Hanani MT (2021) Phytochemical constituents of three species of marine macro-algae from sitio usadda, pangutaran, sulu, Philippines. Am J Appl Chem 9:97\u2013101. https:\/\/doi.org\/10.11648\/j.ajac.20210904.11","journal-title":"Am J Appl Chem"},{"key":"2833_CR19","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/chemosensors9060132","volume":"9","author":"M Carpena","year":"2021","unstructured":"Carpena M, Caleja C, Pereira E, Pereira C, Ciri\u2019c A, Sokovi\u2019c M, Soria-Lopez A, Fraga-Corral M, Simal-Gandara J, Ferreira ICFR, Barros L, Prieto MA (2021) Red seaweeds as a source of nutrients and bioactive compounds: optimization of the extraction. Chemosensors 9:132. https:\/\/doi.org\/10.3390\/chemosensors9060132","journal-title":"Chemosensors"},{"key":"2833_CR20","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s42452-021-04477-9","volume":"3","author":"P Bhuyar","year":"2021","unstructured":"Bhuyar P, Sundararaju S, Rahim MHA, Unpaprom Y, Maniam GP, Govindan N (2021) Antioxidative study of polysaccharides extracted from red (Kappaphycus alvarezii), green (Kappaphycus striatus) and brown (Padina gymnospora) marine macroalgae\/seaweed. SN Appl Sci 3:485. https:\/\/doi.org\/10.1007\/s42452-021-04477-9","journal-title":"SN Appl Sci"},{"key":"2833_CR21","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1016\/j.toxrep.2021.07.006","volume":"8","author":"S Mahendran","year":"2021","unstructured":"Mahendran S, Maheswari P, Sasikala V, Rubika JJ, Pandiarajan J (2021) In vitro antioxidant study of polyphenol from red seaweeds dichotomously branched gracilaria Gracilaria edulis and robust sea moss Hypnea valentiae. Toxicolo Rep 8:1404\u20131411. https:\/\/doi.org\/10.1016\/j.toxrep.2021.07.006","journal-title":"Toxicolo Rep"},{"key":"2833_CR22","doi-asserted-by":"publisher","first-page":"572","DOI":"10.3923\/ijp.2018.572.583","volume":"14","author":"H Omar","year":"2018","unstructured":"Omar H, Al-Judaibiand A, El-Gendy A (2018) Antimicrobial, Antioxidant, Anticancer activity and phytochemical analysis of the red alga, Laurencia papillosa. Int J Pharmacol 14:572\u2013583. https:\/\/doi.org\/10.3923\/ijp.2018.572.583","journal-title":"Int J Pharmacol"},{"issue":"3","key":"2833_CR23","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3390\/antiox11030439","volume":"11","author":"T Vladkova","year":"2022","unstructured":"Vladkova T, Georgieva N, Staneva A, Gospodinova D (2022) recent progress in antioxidant active substances from marine biota. Antioxidants (Basel) 11(3):439. https:\/\/doi.org\/10.3390\/antiox11030439","journal-title":"Antioxidants (Basel)"},{"key":"2833_CR24","doi-asserted-by":"publisher","first-page":"18906","DOI":"10.1038\/s41598-019-55309-1","volume":"9","author":"SH Haq","year":"2019","unstructured":"Haq SH, Al-Ruwaished G, Al-Mutlaq MA, Naji SA, Al-Mogren M, Al-Rashed S, Ain QT, Al-Amro AA, Al-Mussallam A (2019) Antioxidant, anticancer activity and phytochemical analysis of green algae, Chaetomorpha collected from the Arabian Gulf. Sci Rep 9:18906. https:\/\/doi.org\/10.1038\/s41598-019-55309-1","journal-title":"Sci Rep"},{"key":"2833_CR25","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s40995-017-0388-5","volume":"43","author":"A Moshfegh","year":"2019","unstructured":"Moshfegh A, Salehzadeh A, Sadat Shandiz SA, Shafaghi M, Naeemi AS, Salehi S (2019) Phytochemical analysis, antioxidant, anticancer and antibacterial properties of the Caspian Sea red macroalgae, Laurencia caspica. Iran J Sci Technol Trans Sci 43:49\u201356. https:\/\/doi.org\/10.1007\/s40995-017-0388-5","journal-title":"Iran J Sci Technol Trans Sci"},{"key":"2833_CR26","doi-asserted-by":"publisher","first-page":"412","DOI":"10.3389\/fmicb.2018.00412","volume":"9","author":"RM Martins","year":"2018","unstructured":"Martins RM, Nedel F, Guimar\u00e3es VB, da Silva AF, Colepicolo P, de Pereira CMP, Lund RG (2018) Macroalgae extracts from Antarctica have antimicrobial and anticancer potential. Front Microbiol 9:412. https:\/\/doi.org\/10.3389\/fmicb.2018.00412","journal-title":"Front Microbiol"},{"key":"2833_CR27","doi-asserted-by":"publisher","first-page":"71","DOI":"10.3923\/ajaps.2019.71.75","volume":"12","author":"AA Al-amro","year":"2019","unstructured":"Al-amro AA, Al-mutlaq MA, Al-moauther S, Al-tukhaifi N, Bin Othaimeen R, Al-Mutairi N, Al-Rashed S, Al-Malki F, Haq SH (2019) Antioxidant activity of Rhodophyta algae Polysiphonia and Laurencia collected from the Arabian Gulf. Asian J Appl Sci 12:71\u201375. https:\/\/doi.org\/10.3923\/ajaps.2019.71.75","journal-title":"Asian J Appl Sci"},{"key":"2833_CR28","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.3390\/nu12103085","volume":"12","author":"ES Biris-Dorhoi","year":"2020","unstructured":"Biris-Dorhoi ES, Michiu D, Pop CR, Rotar AM, Tofana M, Pop OL, Socaci SA, Farcas AC (2020) Macroalgae-A sustainable source of chemical compounds with biological activities. Nutrients 12:3085. https:\/\/doi.org\/10.3390\/nu12103085","journal-title":"Nutrients"},{"key":"2833_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fmars.2022.832957","volume":"9","author":"S Ghosh","year":"2022","unstructured":"Ghosh S, Sarkar T, Pati S, Kari ZA, Edinur HA, Chakraborty R (2022) Novel bioactive compounds from marine sources as a tool for functional food development. Front Mar Sci 9:832957. https:\/\/doi.org\/10.3389\/fmars.2022.832957","journal-title":"Front Mar Sci"},{"key":"2833_CR30","doi-asserted-by":"publisher","first-page":"19082","DOI":"10.1038\/s41598-021-98461-3","volume":"11","author":"MKA Sobuj","year":"2021","unstructured":"Sobuj MKA, Islam MA, Islam MS, Islam MdM, Mahmud Y, Rafiquzzaman SM (2021) Effect of solvents on bioactive compounds and antioxidant activity of Padina tetrastromatica and Gracilaria tenuistipitata seaweeds collected from Bangladesh. Sci Rep 11:19082. https:\/\/doi.org\/10.1038\/s41598-021-98461-3","journal-title":"Sci Rep"},{"key":"2833_CR31","doi-asserted-by":"publisher","first-page":"603","DOI":"10.22271\/chemi.2020.v8.i2i.8834","volume":"8","author":"JR Shaikh","year":"2020","unstructured":"Shaikh JR, Patil MK (2020) Qualitative tests for preliminary phytochemical screening: an overview. Int J Chem Stud 8:603\u2013608. https:\/\/doi.org\/10.22271\/chemi.2020.v8.i2i.8834","journal-title":"Int J Chem Stud"},{"key":"2833_CR32","doi-asserted-by":"publisher","first-page":"10","DOI":"10.21608\/sjdfs.2021.195585","volume":"11","author":"SE Abu Ahmed","year":"2021","unstructured":"Abu Ahmed SE, Deyab AM, El-Ashry FS, El-Adl MF (2021) Qualitative and quantitative phytochemical composition of Sargassum vulgare at Hurghada Red Sea Coast \u2013 Egypt. SJDFS 11:10\u201314. https:\/\/doi.org\/10.21608\/sjdfs.2021.195585","journal-title":"SJDFS"},{"key":"2833_CR33","volume-title":"Identification of essential oil components by gas chromatography\/mass spectrometry","author":"RP Adams","year":"2009","unstructured":"Adams RP (2009) Identification of essential oil components by gas chromatography\/mass spectrometry, 4th edn. Allured Publishing Corporation, Carol Stream","edition":"4"},{"key":"2833_CR34","first-page":"136","volume":"8","author":"HF Salem","year":"2016","unstructured":"Salem HF, Kharshoum RM (2016) Nanoprecipitation technique for preparation of sterically stabilized risperidone nanosuspension: in vitro and in vivo study. Int J Pharm Pharm 8:136\u2013142","journal-title":"Int J Pharm Pharm"},{"key":"2833_CR35","doi-asserted-by":"publisher","DOI":"10.1093\/ecam\/nep180articlenumber:535172","volume":"2011","author":"E Szliszka","year":"2011","unstructured":"Szliszka E, Czuba ZP, Bronikowska J, Mertas A, Paradysz A, Krol W (2011) Ethanolic extract of propolis augments TRAIL-induced apoptotic death in prostate cancer cells. Evid Based Complement Alternat Med 2011:535172. https:\/\/doi.org\/10.1093\/ecam\/nep180articlenumber:535172","journal-title":"Evid Based Complement Alternat Med"},{"key":"2833_CR36","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/978-1-61779-080-5_20","volume-title":"Cancer cell culture. Methods in molecular biology","author":"J van Meerloo","year":"2011","unstructured":"van Meerloo J, Kaspers GJL, Cloos J (2011) Cell sensitivity assays: the MTT assay. In: Cree I (ed) Cancer cell culture. Methods in molecular biology, vol 731. Humana Press, US, p 237. https:\/\/doi.org\/10.1007\/978-1-61779-080-5_20"},{"key":"2833_CR37","doi-asserted-by":"publisher","DOI":"10.5812\/ijcm.8633","volume":"10","author":"M Rashidi","year":"2017","unstructured":"Rashidi M, Seghatoleslam A, Namavari M, Amiri A, Fahmidehkar MA, Ramezani A, Eftekhar E, Hosseini A, Erfani N, Fakher S (2017) Selective cytotoxicity and apoptosis-induction of Cyrtopodion scabrum extract against digestive cancer cell lines. Int J Cancer Manag 10:e8633. https:\/\/doi.org\/10.5812\/ijcm.8633","journal-title":"Int J Cancer Manag"},{"key":"2833_CR38","doi-asserted-by":"publisher","DOI":"10.1093\/ecam\/neq010","volume":"2011","author":"S Mohan","year":"2011","unstructured":"Mohan S, Bustamam A, Ibrahim S, Al-Zubairi AS, Aspollah M, Abdullah R, Elhassan MM (2011) In vitro ultramorphological assessment of apoptosis on CEMss induced by linoleic acid-rich fraction from Typhonium flagelliforme tuber. Evid Based Complement Alternat Med 2011:421894. https:\/\/doi.org\/10.1093\/ecam\/neq010","journal-title":"Evid Based Complement Alternat Med"},{"key":"2833_CR39","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s13065-016-0234-4","volume":"11","author":"NDA Wageesha","year":"2017","unstructured":"Wageesha NDA, Soysa P, Atthanayake K, Choudhary MI, Ekanayake M (2017) A traditional poly herbal medicine \u201cLe Pana Guliya\u201d induces apoptosis in HepG2 and HeLa cells but not in CC1 cells: an in vitro assessment. Chem Cent J 11:2. https:\/\/doi.org\/10.1186\/s13065-016-0234-4","journal-title":"Chem Cent J"},{"key":"2833_CR40","first-page":"29","volume":"8","author":"R Boly","year":"2016","unstructured":"Boly R, Lamkami T, Lompo M, Dubois J, Guissou IP (2016) DPPH free radical scavenging activity of two extracts from Agelanthus dodoneifolius (Loranthaceae) leaves. Int J Toxicol Pharmacol Res 8:29\u201334","journal-title":"Int J Toxicol Pharmacol Res"},{"key":"2833_CR41","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0308-8146(00)00324-1","volume":"73","author":"M Arnao","year":"2001","unstructured":"Arnao M, Cano A, Acosta M (2001) The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chem 73:239\u2013244. https:\/\/doi.org\/10.1016\/S0308-8146(00)00324-1","journal-title":"Food Chem"},{"key":"2833_CR42","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1007\/s11694-020-00758-w","volume":"15","author":"MKA Sobuj","year":"2021","unstructured":"Sobuj MKA, Islam MdA, Haque MdA, Islam MdM, Alam MdJ, Rafiquzzaman SM (2021) Evaluation of bioactive chemical composition, phenolic, and antioxidant profiling of different crude extracts of Sargassum coriifolium and Hypnea pannosa seaweeds. J Food Meas Charact 15:1653\u20131665. https:\/\/doi.org\/10.1007\/s11694-020-00758-w","journal-title":"J Food Meas Charact"},{"key":"2833_CR43","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.3390\/antiox10091431","volume":"10","author":"LA Tziveleka","year":"2021","unstructured":"Tziveleka LA, Tammam MA, Tzakou O, Roussis V, Ioannou E (2021) Metabolites with antioxidant activity from marine macroalgae. Antioxidants 10:1431. https:\/\/doi.org\/10.3390\/antiox10091431","journal-title":"Antioxidants"},{"key":"2833_CR44","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3390\/md18080384","volume":"18","author":"J Cotas","year":"2020","unstructured":"Cotas J, Leandro A, Monteiro P, Pacheco D, Figueirinha A, Gon\u00e7alves AMM, da Silva GJ, Pereira L (2020) Seaweed phenolics: from extraction to applications. Mar Drugs 18:384. https:\/\/doi.org\/10.3390\/md18080384","journal-title":"Mar Drugs"},{"key":"2833_CR45","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3390\/md17040234","volume":"17","author":"YS Ryu","year":"2019","unstructured":"Ryu YS, Fernando PDSM, Kang KA, Piao MJ, Zhen AX, Kang HK, Koh YS, Hyun JW (2019) Marine compound 3-bromo4,5-dihydroxybenzaldehyde protects skin cells against oxidative damage via the Nrf2\/HO-1 pathway. Mar Drugs 17:234. https:\/\/doi.org\/10.3390\/md17040234","journal-title":"Mar Drugs"},{"key":"2833_CR46","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1021\/acs.orglett.7b03716","volume":"20","author":"K Li","year":"2018","unstructured":"Li K, Wang YF, Li XM, Wang WJ, Ai XZ, Li X, Yang SQ, Gloer JB, Wang BG, Xu T (2018) Isolation, synthesis, and radical-scavenging activity of rhodomelin A, a ureidobromophenol from the marine red alga Rhodomela confervoides. Org Lett 20:417\u2013420. https:\/\/doi.org\/10.1021\/acs.orglett.7b03716","journal-title":"Org Lett"},{"key":"2833_CR47","doi-asserted-by":"publisher","first-page":"400","DOI":"10.4103\/1735-5362.319578","volume":"16","author":"K Karimzadeh","year":"2021","unstructured":"Karimzadeh K, Zahmatkesh A (2021) Phytochemical screening, antioxidant potential, and cytotoxic effects of different extracts of red algae (Laurencia snyderiae) on HT29 cells. Res Pharm Sci 16:400. https:\/\/doi.org\/10.4103\/1735-5362.319578","journal-title":"Res Pharm Sci"},{"key":"2833_CR48","doi-asserted-by":"publisher","first-page":"750","DOI":"10.4103\/pm.pm_24_20","volume":"16","author":"KG Garc\u00eda","year":"2020","unstructured":"Garc\u00eda KG, Delange DM, Rivera YH, Su\u00e1rez YA, Cuesta RG, Riera- Romo M, Olga E, L\u00edvia MD, Da Silva AJRG, Picot L, Guerra IR (2020) Chemical composition and biological potential of a chloroform fraction from the leaves of marine plant Syringodium filiforme K\u00fctzing. Phcog Mag 16:750\u2013756","journal-title":"Phcog Mag"},{"key":"2833_CR49","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.13005\/bpj\/2069","volume":"13","author":"SR Nayaka","year":"2020","unstructured":"Nayaka SR, Sabari Anand JV, Shaik MS, Usha NS (2020) Gas chromatography\u2013mass spectroscopy [GC-MS] analysis and phytochemical screening for bioactive compounds in Caulerpa peltata (Green alga). Biomed Pharmacol J 13:1921\u20131926. https:\/\/doi.org\/10.13005\/bpj\/2069","journal-title":"Biomed Pharmacol J"},{"key":"2833_CR50","first-page":"62","volume":"39","author":"GSE Abou-El-Wafa","year":"2011","unstructured":"Abou-El-Wafa GSE, Shaaban KA, El-Naggar MEE, Shaaban M (2011) Bioactive constituents and biochemical composition of the Egyptian brown alga Sargassum subrepandum (Forsk). Rev latinoam Qu\u00edm 39:62\u201374","journal-title":"Rev latinoam Qu\u00edm"},{"key":"2833_CR51","doi-asserted-by":"publisher","first-page":"247","DOI":"10.32604\/biocell.2022.015966","volume":"46","author":"J Mofeed","year":"2022","unstructured":"Mofeed J, Deyab M, Mohamed M, Moustafa M, Negm S, El-Bilawy E (2022) Antimicrobial activities of three seaweeds extract against some human viral and bacterial pathogens. Biocell 46:247\u2013261. https:\/\/doi.org\/10.32604\/biocell.2022.015966","journal-title":"Biocell"},{"key":"2833_CR52","doi-asserted-by":"publisher","first-page":"7","DOI":"10.32604\/biocell.2018.07002","volume":"42","author":"M Moustafa","year":"2018","unstructured":"Moustafa M, Taha T, Elnouby M, Abu-Saied M, Shati A, AL-Kahtani M, Alrumman S (2018) Feasible design for electricity generation from Chlorella vulgaris using convenient photosynthetic conditions. Biocell 42:7\u201312. https:\/\/doi.org\/10.32604\/biocell.2018.07002","journal-title":"Biocell"},{"key":"2833_CR53","first-page":"913","volume":"8","author":"KG Sonkambale","year":"2021","unstructured":"Sonkambale KG, Katedeshmukh RG, Kumbhar AB, Mane SV, Pawar PA, Kadam JN, Malusare AV (2021) Formulation and evaluation of nanosuspension for enhancing the solubility of poorly soluble antihyperlipidemic drugs. Eur J Mol Clin Med 8:913\u2013928","journal-title":"Eur J Mol Clin Med"},{"key":"2833_CR54","doi-asserted-by":"publisher","first-page":"139","DOI":"10.31838\/ijpr\/2019.11.01.013","volume":"11","author":"VD Sundar","year":"2019","unstructured":"Sundar VD, Divya P, Sridevi P, Akhila K, Dhanaraju MD (2019) Design, formulation and evaluation of nanosuspension for drug delivery of celecoxib. Int J Pharm Res 11:139. https:\/\/doi.org\/10.31838\/ijpr\/2019.11.01.013","journal-title":"Int J Pharm Res"},{"issue":"1","key":"2833_CR55","doi-asserted-by":"publisher","DOI":"10.1088\/1757-899X\/259\/1\/012016","volume":"259","author":"M Dzakwan","year":"2017","unstructured":"Dzakwan M, Pramukantoro GE, Mauludin R, Wikarsa (2017) Formulation and characterization of fisetin nanosuspension. Mater Sci Eng 259(1):012016. https:\/\/doi.org\/10.1088\/1757-899X\/259\/1\/012016","journal-title":"Mater Sci Eng"},{"key":"2833_CR56","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1208\/s12249-020-1621-7","volume":"21","author":"T Liu","year":"2020","unstructured":"Liu T, Yu X, Yin H (2020) Study of top-down and Bottom-up approaches by using design of experiment (DoE) to produce meloxicam nanocrystal capsules. AAPS Pharm Sci Tech 21:79. https:\/\/doi.org\/10.1208\/s12249-020-1621-7","journal-title":"AAPS Pharm Sci Tech"},{"key":"2833_CR57","first-page":"3973","volume":"8","author":"MP Kumar","year":"2017","unstructured":"Kumar MP, Sowmya C, Sekhar KBC (2017) Formulation and in vitro characterization of risperidone nanosuspensions for the enhancement of drug release rate. J Glob Trends Pharm Sci 8:3973\u20133980","journal-title":"J Glob Trends Pharm Sci"},{"key":"2833_CR58","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/j.jddst.2019.03.021","volume":"51","author":"J Jingfu","year":"2019","unstructured":"Jingfu J, Kerong Z, Xue Z, Jinfang M, Xiaojing L, Anya X, Fahuan G (2019) Berberine-loaded solid proliposomes prepared using solution enhanced dispersion by supercritical CO2: sustained release and bioavailability enhancement. J Drug Deliv Sci Techn 51:356\u2013363. https:\/\/doi.org\/10.1016\/j.jddst.2019.03.021","journal-title":"J Drug Deliv Sci Techn"},{"key":"2833_CR59","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.3390\/pharmaceutics13111812","volume":"13","author":"M Elmowafy","year":"2021","unstructured":"Elmowafy M, Shalaby K, Al-Sanea MM, Hendawy OM, Salama A, Ibrahim MF, Ghoneim MM (2021) Influence of stabilizer on the development of Luteolin nanosuspension for cutaneous delivery: an in vitro and in vivo evaluation. Pharmaceutics 13:1812. https:\/\/doi.org\/10.3390\/pharmaceutics13111812","journal-title":"Pharmaceutics"},{"key":"2833_CR60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/938594","volume":"2015","author":"SA Afifi","year":"2015","unstructured":"Afifi SA, Hassan MA, Abdelhameed AS, Elkhodairy KA (2015) Nanosuspension: an emerging trend for bioavailability enhancement of etodolac. Int J Polym Sci 2015:1. https:\/\/doi.org\/10.1155\/2015\/938594","journal-title":"Int J Polym Sci"},{"issue":"4","key":"2833_CR61","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.ejps.2012.08.011","volume":"47","author":"I Ghosh","year":"2012","unstructured":"Ghosh I, Schenck D, Bose S, Ruegger C (2012) Optimization of formulation and process parameters for the production of nanosuspension by wet media milling technique: effect of Vitamin e TPGS and nanocrystal particle size on oral absorption. Eur J Pharm Sci 47(4):718\u2013728. https:\/\/doi.org\/10.1016\/j.ejps.2012.08.011","journal-title":"Eur J Pharm Sci"},{"key":"2833_CR62","doi-asserted-by":"publisher","first-page":"9516156","DOI":"10.1155\/2019\/9516156","volume":"2019","author":"LA Kaledin","year":"2019","unstructured":"Kaledin LA, Tepper F, Vesga Y, Kaledin TG (2019) Boehmite and akaganeite 1D and 2D mesostructures: Synthesis, growth mechanism, ageing characteristics and surface nanoscale roughness effect on water purification. J Nanomater 2019:9516156. https:\/\/doi.org\/10.1155\/2019\/9516156","journal-title":"J Nanomater"},{"issue":"1","key":"2833_CR63","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1080\/10717544.2020.1856224","volume":"28","author":"J Li","year":"2021","unstructured":"Li J, Zengming W, Hui Z, Jing G, Aiping Z (2021) Progress in the development of stabilization strategies for nanocrystal preparations. Drug Deliv 28(1):19\u201336. https:\/\/doi.org\/10.1080\/10717544.2020.1856224","journal-title":"Drug Deliv"},{"key":"2833_CR64","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1590\/S0102-695X2013005000060","volume":"23","author":"EAC Guedes","year":"2013","unstructured":"Guedes EAC, Da Silva TG, Aguiar SJ, De Barros LD, Pinotti LM, Sant\u2019Ana AEG, (2013) Cytotoxic activity of marine algae against cancerous cells. Rev Bras Farmacogn 23:668\u2013673. https:\/\/doi.org\/10.1590\/S0102-695X2013005000060","journal-title":"Rev Bras Farmacogn"},{"key":"2833_CR65","doi-asserted-by":"publisher","first-page":"25","DOI":"10.22159\/ajpcr.2020.v13i7.37764","volume":"13","author":"MM Mithra","year":"2020","unstructured":"Mithra MM, Krishnakumar K, Smitha KN (2020) Herbal nanosuspension: in vitro cancer study against different cell lines. Asian J Pharm Clin Res 13:25\u201329. https:\/\/doi.org\/10.22159\/ajpcr.2020.v13i7.37764","journal-title":"Asian J Pharm Clin Res"},{"key":"2833_CR66","doi-asserted-by":"publisher","first-page":"357","DOI":"10.3390\/ph13110357","volume":"13","author":"A Somaida","year":"2020","unstructured":"Somaida A, Tariq I, Ambreen G, Abdelsalam AM, Ayoub AM, Wojcik M, Dzoyem JP, Bakowsky U (2020) Potent cytotoxicity of four Cameroonian plant extracts on different cancer cell lines. Pharmaceuticals (Basel) 13:357. https:\/\/doi.org\/10.3390\/ph13110357","journal-title":"Pharmaceuticals (Basel)"},{"key":"2833_CR67","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1080\/03639045.2018.1496445","volume":"44","author":"S Rajamani","year":"2018","unstructured":"Rajamani S, Radhakrishnan A, Sengodan T, Thangavelu S (2018) Augmented anticancer activity of naringeninloaded TPGS polymeric nanosuspension for drug resistive MCF-7 human breast cancer cells. Drug Dev Ind Pharm 44:1752\u20131761. https:\/\/doi.org\/10.1080\/03639045.2018.1496445","journal-title":"Drug Dev Ind Pharm"},{"key":"2833_CR68","doi-asserted-by":"publisher","first-page":"3458","DOI":"10.3892\/ol.2018.7769","volume":"15","author":"H Jiang","year":"2018","unstructured":"Jiang H, Li L, Chen L, Li Y, Xia M, Guo P, Yao S, Chen S (2018) Fucosterol exhibits selective antitumor anticancer activity against Hela human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR\/PI3K\/Akt signalling pathway. Oncol Lett 15:3458\u20133463. https:\/\/doi.org\/10.3892\/ol.2018.7769","journal-title":"Oncol Lett"},{"key":"2833_CR69","doi-asserted-by":"publisher","unstructured":"Mofeed J, Deyab M, Abd El-Naser S, Ward F (2021) In vitro anticancer activity of five marine seaweeds extract from Egypt against human breast and colon cancer cell lines. Research Square. May 6th. https:\/\/doi.org\/10.21203\/rs.3.rs-462221\/v1.","DOI":"10.21203\/rs.3.rs-462221\/v1"},{"key":"2833_CR70","doi-asserted-by":"publisher","first-page":"60","DOI":"10.4103\/0973-1296.93327","volume":"8","author":"M Khanavi","year":"2012","unstructured":"Khanavi M, Gheidarloo R, Sadati N, Ardekani MS, Nabavi SMB, Tavajohi S, Ostad SN (2012) Cytotoxicity of fucosterol containing fraction of marine algae against breast and colon carcinoma cell line. Pharmacogn Mag 8:60\u201364. https:\/\/doi.org\/10.4103\/0973-1296.93327","journal-title":"Pharmacogn Mag"},{"key":"2833_CR71","doi-asserted-by":"publisher","first-page":"265","DOI":"10.3109\/10717544.2010.536271","volume":"18","author":"FF Feng","year":"2011","unstructured":"Feng FF, Zhang DR, Tian KL, Lou HY, Qi XL, Wang YC, Duan CX, Jia LJ, Wang FH, Liu Y (2011) Growth inhibition and induction of apoptosis in MCF-7 breast cancer cells by oridonin nanosuspension. Drug Deliv 18:265\u2013271. https:\/\/doi.org\/10.3109\/10717544.2010.536271","journal-title":"Drug Deliv"},{"key":"2833_CR72","doi-asserted-by":"publisher","first-page":"775","DOI":"10.17957\/IJAB\/15.0956","volume":"21","author":"F Zafar","year":"2019","unstructured":"Zafar F, Jahan N, Khalil-Ur-Rahman MRA, Ali S (2019) Comparative evaluation of biological activities of native and nanosuspension of Terminalia arjuna. Int J Agric Biol 21:775\u2013785. https:\/\/doi.org\/10.17957\/IJAB\/15.0956","journal-title":"Int J Agric Biol"},{"key":"2833_CR73","doi-asserted-by":"publisher","first-page":"5753391","DOI":"10.1155\/2021\/5753391","volume":"2021","author":"Y Kumar","year":"2021","unstructured":"Kumar Y, Tarafdar A, Badgujar PC (2021) Seaweed as a source of natural antioxidants: therapeutic activity and food applications. J Food Qual 2021:5753391. https:\/\/doi.org\/10.1155\/2021\/5753391","journal-title":"J Food Qual"},{"key":"2833_CR74","doi-asserted-by":"publisher","first-page":"54","DOI":"10.36468\/pharmaceutical-sciences.622","volume":"82","author":"TA Powar","year":"2020","unstructured":"Powar TA, Hajare AA (2020) Lyophilized ethinylestradiol nanosuspension: Fabrication, characterization and evaluation of in vitro anticancer and pharmacokinetic study. Indian J Pharm Sci 82:54\u201365. https:\/\/doi.org\/10.36468\/pharmaceutical-sciences.622","journal-title":"Indian J Pharm Sci"},{"key":"2833_CR75","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12951-019-0565-0","volume":"18","author":"H Li","year":"2020","unstructured":"Li H, Liu B, Ao H, Fu J, Wang Y, Feng Y, Guo Y, Wang X (2020) Soybean lecithin stabilizes disulfiram nanosuspensions with a high drug-loading content: remarkably improved antitumor efficacy. J Nanobiotechnol 18:4. https:\/\/doi.org\/10.1186\/s12951-019-0565-0","journal-title":"J Nanobiotechnol"},{"key":"2833_CR76","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquaculture.2020;735088","volume":"522","author":"J Vega","year":"2020","unstructured":"Vega J, \u00c1lvarez-G\u00f3mez F, G\u00fcenaga L, Figueroa FL, G\u00f3mez-Pinchetti GL (2020) Antioxidant activity of extracts from marine macroalgae, wild-collected and cultivated, in an integrated multi-trophic aquaculture system. Aquaculture 522:735088. https:\/\/doi.org\/10.1016\/j.aquaculture.2020;735088","journal-title":"Aquaculture"},{"key":"2833_CR77","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.3390\/ijms21031131","volume":"21","author":"IR Ilyasov","year":"2020","unstructured":"Ilyasov IR, Beloborodov VL, Selivanova IA, Terekhov RP (2020) ABTS\/DPPH decolorization assay of antioxidant capacity reaction pathways. Int J Mol Sci 21:1131. https:\/\/doi.org\/10.3390\/ijms21031131","journal-title":"Int J Mol Sci"},{"key":"2833_CR78","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2019.101482","volume":"55","author":"ML Mancaa","year":"2020","unstructured":"Mancaa ML, Laia F, Pireddua R, Valentia D, Schlicha M, Pinib E, Ailunoc G, Faddaa AM, Sinicoa C (2020) Impact of nanosizing on dermal delivery and antioxidant activity of quercetin nanocrystals. J Drug Deliv Sci Tech 55:101482. https:\/\/doi.org\/10.1016\/j.jddst.2019.101482","journal-title":"J Drug Deliv Sci Tech"}],"container-title":["Bioprocess and Biosystems Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00449-022-02833-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00449-022-02833-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00449-022-02833-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T03:07:09Z","timestamp":1674788829000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00449-022-02833-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":78,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["2833"],"URL":"https:\/\/doi.org\/10.1007\/s00449-022-02833-6","relation":{},"ISSN":["1615-7591","1615-7605"],"issn-type":[{"value":"1615-7591","type":"print"},{"value":"1615-7605","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"assertion":[{"value":"23 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}