Abstract
In this study, the controlled synthesis of microcarriers and CpE loading were aimed to achieve by microfluidic system. The effect of temperature on chitosan in the stabilization of silver nanoparticles, microcarrier size and the encapsulation efficiency was measured. Encapsulation was achieved by the controlled rapid mixing in polymethyl-methacrylate (PMMA) microfluidic chip. The CpE was found to contain primary and secondary phenols in the phytochemical screening. The capping property of chitosan was achieved by heating reaction mixture in polytetrafluoroethylene (PTFE) tube to get the stabilized silver nanoparticles which were found to be embedded in chitosan microspheres of size 23.7 µm on average. Fourier-transform infrared (FTIR) and ultraviolet–visible (UV–Vis) spectroscopy results indicated the successful encapsulation of CpE in microcarriers. The average percentage encapsulation efficiency (% EE) of CsAg was found to be 77.125 ± 6.9%. The CpE-loaded microcarriers had shown significant anti-oxidant activity (p < 0.01). CpE-loaded microcarriers were evaluated to have robust cytotoxicity against 4T1 breast cancer cells at very low dose (IC50 = 42.53 µg/mL), which inhibited 95% of cancer cells viability. These results confer that microfluidic system plays an important role in the formation of CpE-loaded CsAg microcarriers that could effectively (p < 0.0001) kill the breast cancer cells.
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References
Abaza A, Mahmoud GA, Hegazy EA et al (2018) Cytotoxic effect of chitosan based nanocomposite synthesized by radiation: in vitro liver and breast cancer cell line. J Pharm Pharmacol. https://doi.org/10.17265/2328-2150/2018.04.002
Adhikari HS, Yadav PN (2018) Anticancer activity of chitosan, chitosan derivatives, and their mechanism of action. Int J Biomater 2018:1–29. https://doi.org/10.1155/2018/2952085
Akmaz S, Dilaver Adgüzel E, Yasar M, Erguven O (2013) The effect of ag content of the chitosan-silver nanoparticle composite material on the structure and antibacterial activity. Adv Mater Sci Eng 2013:6. https://doi.org/10.1155/2013/690918
Alzahrani HS, Swed Alzahrani H, Mutwakil M et al (2017) Anticancer and antibacterial activity of Calotropis procera leaf extract. J Basic Appl Sci Res 7:18–25
Alzahrani HS, Almalki SA, Rizgallah MR (2019) Study of the cytotoxic effect of Calotropis procera on breast cancer cell line T47D in vitro: a traditional remedy. Int J Sci Innov 7:107–112. https://doi.org/10.32594/IJSI
American Cancer Society (2019) Cancer facts & figures 2019: Atlanta. Am cancer Soc 1–76
Amoyav B, Benny O (2018) Controlled and tunable polymer particles’ production using a single microfluidic device. Appl Nanosci 8:905–914. https://doi.org/10.1007/s13204-018-0790-0
Bilal M, Zhao Y, Rasheed T et al (2019) Biogenic nanoparticle–chitosan conjugates with antimicrobial, antibiofilm, and anticancer potentialities: development and characterization. Int J Environ Res Public Health 16:598–612. https://doi.org/10.3390/ijerph16040598
Chandirika JU, Sindhu R, Selvakumar S, Annadurai G (2018) Herbal extract encapsulated in chitosan nanoparticles: a novel strategy for the treatment of urolithiasis. INDO Am J Pharm Sci 1:1955–1961. https://doi.org/10.5281/zenodo.1212445
Chen Q, Jiang H, Ye H et al (2014) Preparation, antibacterial, and antioxidant activities of silver/chitosan composites. J Carbohydr Chem 33:298–312. https://doi.org/10.1080/07328303.2014.931962
Dada AO, Ojediran OJ, Dada FE et al (2017) Green synthesis and characterization of silver nanoparticles using Calotropis procera extract. Orig Res Artic J Appl Chem Sci Int 8:137–143
Damiati S, Kompella UB, Damiati SA, Kodzius R (2018) Microfluidic devices for drug delivery systems and drug screening. Genes (Basel) 9:103. https://doi.org/10.3390/genes9020103
Ellahi R, Hussain F, Asad Abbas S et al (2020) Study of two-phase newtonian nanofluid flow hybrid with hafnium particles under the effects of slip. Inventions 5:6. https://doi.org/10.3390/inventions5010006
Farouk AEA, Ahamed NT, Alzahrani O et al (2016) Antimicrobial activities evaluation from the extracts of leaves, flowers, fruits and latex of calotropis procera from Taif. Int J Curr Microbiol Appl Sci 5:240–256. https://doi.org/10.20546/ijcmas.2016.511.026
Govindan S, Nivethaa EAK, Saravanan R et al (2012) Synthesis and characterization of chitosan–silver nanocomposite. Appl Nanosci. https://doi.org/10.1007/s13204-012-0109-5
Gul R, Jan SU, Faridullah S et al (2017) Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from ephedra intermedia indigenous to balochistan. Sci World J. https://doi.org/10.1155/2017/5873648
Hintzer K, Zipplies T, Carlson DP, Schmiegel W (2016) Fluoropolymers, organic. Ullmann’s encyclopedia of industrial chemistry. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 1–55
Hoseinzadeh S, Ramezani AH (2019) Investigation of Ta/NII-WO 3 /FTO structures as a semiconductor for the future of nanodevices. J Nanoelectron Optoelectron 14:1413–1419. https://doi.org/10.1166/jno.2019.2564
Hoseinzadeh S, Ghasemiasl R, Bahari A, Ramezani AH (2017a) n-type WO3 semiconductor as a cathode electrochromic material for ECD devices. J Mater Sci Mater Electron 28:14446–14452. https://doi.org/10.1007/s10854-017-7306-7
Hoseinzadeh S, Ghasemiasl R, Bahari A, Ramezani AH (2017b) The injection of Ag nanoparticles on surface of WO3 thin film: enhanced electrochromic coloration efficiency and switching response. J Mater Sci Mater Electron 28:14855–14863. https://doi.org/10.1007/s10854-017-7357-9
Hoseinzadeh S, Ghasemiasl R, Bahari A, Ramezani AH (2018) Effect of post-annealing on the electrochromic properties of layer-by-layer arrangement FTO-WO3-Ag-WO3-Ag. J Electron Mater 47:3552–3559. https://doi.org/10.1007/s11664-018-6199-4
Huang WY, Cai YZ, Zhang Y (2010) Natural phenolic compounds from medicinal herbs and dietary plants: potential use for cancer prevention. Nutr Cancer 62:1–20. https://doi.org/10.1080/01635580903191585
Hussein-Al-Ali SH, Kura A, Hussein MZ, Fakurazi S (2018) Preparation of chitosan nanoparticles as a drug delivery system for perindopril erbumine. Polym Compos 39:544–552. https://doi.org/10.1002/pc.23967
Jacob S, Nair AB, Shah J (2020) Emerging role of nanosuspensions in drug delivery systems. Biomater Res 24
Jain PK, Soni A, Jain P, Bhawsar J (2016) Phytochemical analysis of Mentha spicata plant extract using UV–VIS, FTIR and GC/MS technique. J Chem Pharm Res 8:1–6
Kalaivani R, Maruthupandy M, Muneeswaran T et al (2018) Synthesis of chitosan mediated silver nanoparticles (Ag NPs) for potential antimicrobial applications. Front Lab Med 2:30–35. https://doi.org/10.1016/j.flm.2018.04.002
Kar D, Pattnaik PK, Pattnaik B, Kuanar A (2018) Antimicrobial analysis of different parts extract in different solvent system of a waste weed-Calotropis procera. Asian J Pharm Clin Res 11:227–231. https://doi.org/10.22159/ajpcr.2018.v11i2.21081
Kaur H (2018) Review on the extraction methods used in medicinal plants. Int J Adv Manag Technol Eng Sci
Kesente M, Kavetsou E, Roussaki M et al (2017) Encapsulation of olive leaves extracts in biodegradable PLA nanoparticles for use in cosmetic formulation. Bioengineering 4:1–14. https://doi.org/10.3390/bioengineering4030075
Khanzada SK, Shaikh W, Kazi TG et al (2008) Analysis of fatty acid, elemental and total protein of Calotropis procera medicinal plant from Sindh, Pakistan. Pakistan J Bot 40:1913–1921
Kong T, Wu J, Yeung KWK et al (2013) Microfluidic fabrication of polymeric core–shell microspheres for controlled release applications. Biomicrofluidics. https://doi.org/10.1063/1.4819274
Kummari SVKR, Kummara MR, Palem RR et al (2015) Chitosan-poly(aminopropyl/phenylsilsesquioxane) hybrid nanocomposite membranes for antibacterial and drug delivery applications. Polym Int 64:293–302. https://doi.org/10.1002/pi.4789
Li J, Cai C, Li J et al (2018) Chitosan-based nanomaterials for drug delivery. Molecules 23:1–26. https://doi.org/10.3390/molecules23102661
Maslanka Figueroa S, Fleischmann D, Beck S, Goepferich A (2020) Thermodynamic, spatial and methodological considerations for the manufacturing of therapeutic polymer nanoparticles. Pharm Res 37:59. https://doi.org/10.1007/s11095-020-2783-4
Medina-Sánchez M, Xu H, Schmidt OG (2018) Micro- and nano-motors: the new generation of drug carriers. Ther Deliv 9:303–316. https://doi.org/10.4155/tde-2017-0113
Mohan CO, Gunasekaran S, Ravishankar CN (2019) Chitosan-capped gold nanoparticles for indicating temperature abuse in frozen stored products. NPJ Sci Food 3:2. https://doi.org/10.1038/s41538-019-0034-z
Morsy N, Al Sherif EA, Abdel-Rassol TMA (2016) Phytochemical analysis of Calotropis procera with antimicrobial activity investigation. Main Gr Chem 15:267–273. https://doi.org/10.3233/MGC-160206
Munin A, Edwards-Lévy F (2011) Encapsulation of natural polyphenolic compounds; a review. Pharmaceutics 3:793–829. https://doi.org/10.3390/pharmaceutics3040793
Murugan K, Anitha J, Dinesh D et al (2016) Fabrication of nano-mosquitocides using chitosan from crab shells: Impact on non-target organisms in the aquatic environment. Ecotoxicol Environ Saf 132:318–328. https://doi.org/10.1016/j.ecoenv.2016.06.021
Mutluq Alkammash N (2017) Synthesis of silver nanoparticles from artemisia sieberiand calotropis procera medical plant extracts and their characterization using SEM analysis. Biosci Biotechnol Res Asia 14:521–526. https://doi.org/10.13005/bbra/2474
Nair R, Reddy BH, Kumar CKA, Kumar KJ (2009) Application of chitosan microspheres as drug carriers: a review. J Pharm Sci Res 1:1–12
Najafi-Ashtiani H, Bahari A, Gholipour S, Hoseinzadeh S (2018) Structural, optical and electrical properties of WO3–Ag nanocomposites for the electro-optical devices. Appl Phys A Mater Sci Process 124:1–9. https://doi.org/10.1007/s00339-017-1412-5
Nate Z, Moloto MJ, Mubiayi PK, Sibiya PN (2018) Green synthesis of chitosan capped silver nanoparticles and their antimicrobial activity. MRS Adv 3:2505–2517. https://doi.org/10.1557/adv.2018.368
Nayak D, Minz AP, Ashe S et al (2016) Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: characterization and cytotoxic effect on MCF-7 breast cancer cell lines. J Colloid Interface Sci 470:142–152. https://doi.org/10.1016/j.jcis.2016.02.043
Obayemi JD, Soboyejo WO, Odusanya OS, et al (2014) Abstract B40: Injectable multifunctional biodegradable polymeric microspheres for localized drug delivery in breast cancer treatment. In: Cancer Epidemiology and Prevention Biomarkers. American Association for Cancer Research (AACR), pp B40–B40
Oliveira RN, Mancini MC, de Oliveira FCS et al (2016) FTIR analysis and quantification of phenols and flavonoids of five commercially available plants extracts used in wound healing. Matéria (Rio Janeiro) 21:767–779. https://doi.org/10.1590/s1517-707620160003.0072
Palem RR, Saha N, Shimoga GD et al (2018) Chitosan–silver nanocomposites: new functional biomaterial for health-care applications. Int J Polym Mater Polym Biomater 67:1–10. https://doi.org/10.1080/00914037.2017.1291516
Queiroz MF, Melo KRT, Sabry DA et al (2015) Does the use of chitosan contribute to oxalate kidney stone formation? Mar Drugs 13:141–158. https://doi.org/10.3390/md13010141
Rani R, Sharma D, Chaturvedi M, Yadav JP (2018) Phytochemical analysis, antibacterial and antioxidant activity of Calotropis procera and Calotropis gigantea. Nat Prod J. https://doi.org/10.2174/2210315508666180608081407
Ruch RJ, Cheng SJ, Klaunig JE (1989) Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from chinese green tea. Carcinogenesis 10:1003–1008. https://doi.org/10.1093/carcin/10.6.1003
Salari E, Peyghambarzadeh SM, Sarafraz MM, Hormozi F (2016) Boiling thermal performance of TiO2 aqueous nanofluids as a coolant on a disc copper block. Period Polytech Chem Eng 60:106–122. https://doi.org/10.3311/ppch.8262
Salari E, Peyghambarzadeh SM, Sarafraz MM et al (2017) Thermal behavior of aqueous iron oxide nano-fluid as a coolant on a flat disc heater under the pool boiling condition. Heat Mass Transf und Stoffuebertragung 53:265–275. https://doi.org/10.1007/s00231-016-1823-4
Samy RP, Rajendran P, Li F et al (2012a) Identification of a novel Calotropis procera protein that can suppress tumor growth in breast cancer through the suppression of NF-κB pathway. PLoS ONE 7:1–14. https://doi.org/10.1371/journal.pone.0048514
Samy RP, Rajendran P, Li F et al (2012b) Identification of a novel Calotropis procera protein that can suppress tumor growth in breast cancer through the suppression of NF-κB pathway. PLoS ONE. https://doi.org/10.1371/journal.pone.0048514
Sarafraz MM, Arjomandi M (2018a) Demonstration of plausible application of gallium nano-suspension in microchannel solar thermal receiver: experimental assessment of thermo-hydraulic performance of microchannel. Int Commun Heat Mass Transf 94:39–46. https://doi.org/10.1016/j.icheatmasstransfer.2018.03.013
Sarafraz MM, Arjomandi M (2018b) Thermal performance analysis of a microchannel heat sink cooling with copper oxide-indium (CuO/In) nano-suspensions at high-temperatures. Appl Therm Eng 137:700–709. https://doi.org/10.1016/j.applthermaleng.2018.04.024
Sarafraz MM, Hormozi F, Kamalgharibi M (2014) Sedimentation and convective boiling heat transfer of CuO–water/ethylene glycol nanofluids. Heat Mass Transf und Stoffuebertragung 50:1237–1249. https://doi.org/10.1007/s00231-014-1336-y
Shahzadi I, Bashir M, Bashir S, Inayat MH (2018) Thermally assisted coating of PVA for hydrophilic surface modification of PMMA microchannel for oil in water emulsion. In: Proceedings of 2018 15th International Bhurban Conference on Applied Sciences and Technology, IBCAST 2018. pp 51–54
Singh M, Sinha I, Mandal RK (2009) Role of pH in the green synthesis of silver nanoparticles. Mater Lett 63:425–427. https://doi.org/10.1016/j.matlet.2008.10.067
Stoica R, Şomoghi R, Ion RM (2013) Preparation of chitosan—tripolyphosphate nanoparticles for the encapsulation of polyphenols extracted from rose hips. Dig J Nanomater Biostruct 8:955–963
Tsao CW, DeVoe DL (2009) Bonding of thermoplastic polymer microfluidics. Microfluid Nanofluidics 6:1–6. https://doi.org/10.1007/s10404-008-0361-x
Van PhuD, Duy NN, Quoc LA, Hien NQ (2009) The effect of ph and molecular weight of chitosan on silver nanoparticles synthesized by irradiation. Res Dev Cent Radiat Technol 47:47–52
Venkatesham M, Ayodhya D, Madhusudhan A et al (2014) A novel green one-step synthesis of silver nanoparticles using chitosan: catalytic activity and antimicrobial studies. Appl Nanosci. https://doi.org/10.1007/s13204-012-0180-y
Verma VN (2014) The chemical study of calotropis. Int Lett Chem Phys Astron 1:74–90. https://doi.org/10.18052/www.scipress.com/ILCPA.20.74
Vimala K, Mohan YM, Varaprasad K et al (2011) Fabrication of curcumin encapsulated chitosan-PVA silver nanocomposite films for improved antimicrobial activity. J Biomater Nanobiotechnol 2:55–64. https://doi.org/10.4236/jbnb.2011.21008
Wang X, Liu J, Wang P et al (2018) Synthesis of biomaterials utilizing microfluidic technology. Genes (Basel) 9:E283. https://doi.org/10.3390/genes9060283
Wei W, Mao X, Ortiz LA, Sadoway DR (2011) Oriented silver oxide nanostructures synthesized through a template-free electrochemical route. J Mater Chem 21:432–438. https://doi.org/10.1039/c0jm02214d
Yang CH, Wang LS, Chen SY et al (2016) Microfluidic assisted synthesis of silver nanoparticle–chitosan composite microparticles for antibacterial applications. Int J Pharm 510:493–500. https://doi.org/10.1016/j.ijpharm.2016.01.010
Yousefzadeh S, Rajabi H, Ghajari N et al (2019) Numerical investigation of mixed convection heat transfer behavior of nanofluid in a cavity with different heat transfer areas. J Therm Anal Calorim. https://doi.org/10.1007/s10973-019-09018-6
Zhou N, Li D, Yang D (2014) Morphology and composition controlled synthesis of flower-like silver nanostructures. Nanoscale Res Lett 9:1–6. https://doi.org/10.1186/1556-276X-9-302
Zugic A, Tadic V, Savic S (2020) Nano-and microcarriers as drug delivery systems for usnic acid: review of literature. Pharmaceutics. https://doi.org/10.3390/pharmaceutics12020156
Acknowledgements
This research is supported by Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad, Pakistan. Authors are grateful to Mr. Asghar Ali and Mr. Islam Khattak for providing technical support in various stages of research. We extend our heartful thanks to Engr. Usman Aftab for his significant assistance in proofreading of this research. We are also thankful to Malik Ihsanullah Khan from Division of Molecular Medicine (USTC) for helping in preparation of plant extract and its phytochemical analysis. The authors would like to pay a special thanks to University of Science and Technology of China for providing chitosan (CAS: 9012-76-4, Sigma).
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Aftab, A., Bashir, S., Rafique, S. et al. Microfluidic platform for encapsulation of plant extract in chitosan microcarriers embedding silver nanoparticles for breast cancer cells. Appl Nanosci 10, 2281–2293 (2020). https://doi.org/10.1007/s13204-020-01433-8
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DOI: https://doi.org/10.1007/s13204-020-01433-8