Development of Chamomile Lyotropic Liquid Crystal Nanoparticle: Anti-Inflammatory Potential
Abstract
Chamomile is renowned for its anti-inflammatory properties. Lyotropic Liquid Crystal Nanoparticle (LLCN) offers better enhancement of the bioavailability and efficacy of natural products. This study evaluated the LLCN system’s effectiveness in improving chamomile extract’s anti-inflammatory activity and compliance with nanoparticle standards. Chamomile 70% ethanol extract was prepared, and the total phenolic and flavonoid content was measured. The extract was formulated into LLCN, and the particle size, polydispersity index, zeta potential, stability, and entrapment efficiency were evaluated. Anti-inflammatory activity was tested in vitro using the protein denaturation inhibition method. The extract showed high phenolic and flavonoid content. The characterisation results demonstrated that the LLCN system met the required specifications, exhibiting particle size values of 230.366±3.412 nm, polydispersity index of 0.217±0.034, a zeta potential of -23.763±0.756 mV, and an entrapment efficiency of 84.060%±0.100. Stability testing indicated that storage at 4°C was more effective than room temperature, preserving a smaller particle size and improving overall stability. The LLCN system significantly enhanced the extract’s anti-inflammatory activity, as demonstrated by a lower IC50 value than the viscous extract. In conclusion, the LLCN system enhances the therapeutic potential of chamomile extract and represents a promising strategy for developing phytochemical-based anti-inflammatory formulations.
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References
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Nieri V, de Souza JF, Segato TCM, Caetano ÉLA, Leite FG, Chaud MV, et al. Effects of Green Tea and Green Tea Incorporated in Nanoparticle Lyotropic Liquid Crystal on Exercise Adaptations: A High-Intensity Interval Training Pre-Clinical Study. Nutrients. 2022;14(15). Crossref
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Nabila, Sumaiyah, Salim E. Dried Samples Characterization and Determination of Total Phenol and Flavonoid of Ethanol Extract from Musa paradisiaca l. Fruit Peel. World Journal of Advanced Research and Reviews. 2022;16(3):941-946. Crossref
Ramadhan H, Forestryana D, Jamaludin W Bin, Palguno SK. Antibacterial Activity of Liquid Crystal Nanoparticles Gel of Binjai Leaves Methanol Extract (Mangifera caesia Jack. Ex. Wall.) Against Propionibacterium Acnes. International Journal of Applied Pharmaceutics. 2022;14(5):67–71. Crossref
Zulfa E, Novianto D, Setiawan D. Formulasi Nanoemulsi Natrium Diklofenak dengan Variasi Kombinasi Tween 80 Dan Span 80: Kajian Karakteristik Fisik Sediaan. Media Farmasi Indonesia. 2019;14(1):1471-1477. Crossref
Sun X, Pan C, Ying Z, Yu D, Duan X, Huang F, et al. Stabilization of Zein Nanoparticles with K-Carrageenan and Tween 80 for Encapsulation of Curcumin. Int J Biol Macromol. 2020;146:549–559. Crossref
Akib NI, Hendra NS, Purnama Putri AE, Armadhani I, Tendri Adjeng AN, Mahmudah R. Preparation of Phytosome of Kersen Leaves (Muntingia calabura L.) Ethanol Extract as Antioxidant. Jurnal Farmasi Sains dan Praktis. 2021;7(3):393–404. Crossref
Farida Y, Rahmat D, Amanda AW. Anti-Inflammation Activity Test of Nanoparticles Ethanol Extract of Temulawak Rhizome (Curcuma xanthorrhiza Roxb.) with Protein Denaturation Inhibition Method. Jurnal Ilmu Kefarmasian Indonesia. 2018;16(2):225-230. Crossref
Silvestrini AVP, Garcia Praça F, Leite MN, de Abreu Fantini MC, Frade MAC, Badra Bentley MVL. Liquid Crystalline Nanoparticles Enable a Multifunctional Approach for Topical Psoriasis Therapy by Co-delivering Triptolide and siRNAs. Int J Pharm. 2023;640. Crossref
Ball R, Bajaj P, Whitehead KA. Achieving Long-term Stability of Lipid Nanoparticles: Examining the Effect of pH, Temperature, and Lyophilization. Int J Nanomedicine. 2016;12:305–315. Crossref
Supraba W, Juliantoni Y, Ananto AD. The Effect of Stirring Speeds to the Entrapment Efficiency in a Nanoparticles Formulation of Java Plum's Seed Ethanol Extract (Syzygium cumini). Acta Chimica Asiana. 2021;4(1):197–202. Crossref
Ramadhan H, Helmina R, Fahriana Y, Muthia R, Fitryanti, Forestryana D. Formulasi Gel Ekstrak Metanol Daun Balik Angin (Alphitonia incana (Roxb.) Teijsm. & Binn. Ex Kurz). Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2024;11(2):98–113. Crossref
Ma Q, Jiang JG, Yuan X, Qiu K, Zhu W. Comparative Antitumor and Anti-inflammatory Effects of Flavonoids, Saponins, Polysaccharides, Essential Oil, Coumarin and Alkaloids from Cirsium japonicum DC. Food and Chemical Toxicology. 2019;125:422–429. Crossref
Shabir S, Yousuf S, Singh SK, Vamanu E, Singh MP. Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: an Attenuation of Cellular, Biochemical, and Organismal Markers. Antioxidants. 2022;11(8):1623. Crossref
Tao Y, Wu D, Zhang QA, Sun DW. Ultrasound-assisted Extraction of Phenolics from Wine Lees: Modeling, Optimization and Stability of Extracts during Storage. Ultrason Sonochem. 2014;21(2):706–715. Crossref
Yousefbeyk F, Hemmati G, Gholipour Z, Ghasemi S, Evazalipour M, Schubert C, et al. Phytochemical Analysis, Antioxidant, Cytotoxic, and Antimicrobial Activities of Golden Chamomile (Matricaria Aurea (Loefl.) Schultz Bip). Zeitschrift für Naturforschung C. 2022;77(7–8):331–342. Crossref
Sah A, Naseef PP, Kuruniyan MS, Jain GK, Zakir F, Aggarwal G. A Comprehensive Study of Therapeutic Applications of Chamomile. Pharmaceuticals. 2022;15(10). Crossref
Andriani R, Malaka MH, Jubir I, Aspadiah V, Fristiohady A. Review Jurnal: Pemanfaatan Etosom Sebagai Bentuk Sediaan Patch. Farmasains : Jurnal Ilmiah Ilmu Kefarmasian. 2021;8(1):45–57. Crossref
Sharma RK, Ganesan P, Tyagi V, Metselaar H, Sandaran SC. Thermal Properties and Heat Storage Analysis of Palmitic Acid-TiO2 Composite as Nano-Enhanced Organic Phase Change Material (NEOPCM). Appl Therm Eng. 2016;99:1254–1262. Crossref
Zhai J, Fong C, Tran N, Drummond CJ. Non-Lamellar Lyotropic Liquid Crystalline Lipid Nanoparticles for the Next Generation of Nanomedicine. ACS Nano. 2019;13(6):6178–6206. Crossref
Mursal ILP, Fajriyani A, Nurfirzatulloh I, Insani M, Shafira RA. Jenis-Jenis dan Ukuran Nanopartikel dalam Sistem Penghantaran Obat yang Baik : Literature Review Articel. Jurnal Ilmiah Wahana Pendidikan. 2023;16(9):457–462. Crossref
Rahmawanty D, Anwar E, Bahtiar A. Utilization of Chitosan Cross-Linked with Tripolyphosphate as The Excipient of Snakehead Fish (Channa striatus) Gel. Jurnal Ilmu Kefarmasian Indonesia. 2015;13(1):76–81. Crossref
Juliantoni Y, Hajrin W, Subaidah WA. Nanoparticle Formula Optimization of Juwet Seeds Extract (Syzygium cumini) using Simplex Lattice Design Method. Jurnal Biologi Tropis. 2020;20(3):416–422. Crossref
Patel PJ, Gohel MC, Acharya SR. Exploration of Statistical Experimental Design to Improve Entrapment Efficiency of Acyclovir in Poly (d, l) Lactide Nanoparticles. Pharm Dev Technol. 2014;19(2):200–212. Crossref
Ganesan P, Ramalingam P, Karthivashan G, Ko YT, Choi DK. Recent Developments in Solid Lipid Nanoparticle and Surface-Modified Solid Lipid Nanoparticle Delivery Systems for Oral Delivery of Phyto-Bioactive Compounds in Various Chronic Diseases. Int J Nanomedicine. 2018;13:1569–1583. Crossref
Jaiswal P, Gidwani B, Vyas A. Nanostructured Lipid Carriers and Their Current Application in Targeted Drug Delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):27–40. Crossref
Benedini L, Placente D, Ruso J, Messina P. Adsorption/Desorption Study of Antibiotic and Anti-inflammatory Drugs Onto Bioactive Hydroxyapatite Nano-Rods. Mater Sci Eng C. 2019;99:180–190. Crossref
Alnuqaydan AM, Almutary AG, Azam M, Manandhar B, De Rubis G, Madheswaran T, et al. Phytantriol-Based Berberine-Loaded Liquid Crystalline Nanoparticles Attenuate Inflammation and Oxidative Stress in Lipopolysaccharide-Induced RAW264.7 Macrophages. Nanomaterials. 2022;12(23):4312. Crossref
Shin SA, Joo BJ, Lee JS, Ryu G, Han M, Kim WY, et al. Phytochemicals as Anti-inflammatory Agents in Animal Models of Prevalent Inflammatory Diseases. Molecules. 2020;25(24):5932. Crossref
Ribeiro D, Freitas M, Tomé SM, Silva AMS, Laufer S, Lima JLFC, et al. Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood. Inflammation. 2015;38(2):858–870. Crossref
Asadi Z, Ghazanfari T, Hatami H. Anti-inflammatory Effects of Matricaria chamomilla Extracts on BALB/c Mice Macrophages and Lymphocytes. Iran J Allergy Asthma Immunol. 2020;Supple.1(19):63–73. Crossref
Mohebali S, Nasri S, Asghari S, Karimi Dehbehi F, Heydarizad M, Kordestani F, et al. Antinociceptive and Anti-Inflammatory Effects of Matricaria Chamomilla L. in Male Mice. Complementary Medicine Journal. 2013;3(2):451–461.
Singh O, Khanam Z, Misra N, Srivastava M. Chamomile (Matricaria chamomilla L.): An Overview. Pharmacogn Rev. 2011;5(9):82-95. Crossref
Nieri V, de Souza JF, Segato TCM, Caetano ÉLA, Leite FG, Chaud MV, et al. Effects of Green Tea and Green Tea Incorporated in Nanoparticle Lyotropic Liquid Crystal on Exercise Adaptations: A High-Intensity Interval Training Pre-Clinical Study. Nutrients. 2022;14(15). Crossref
Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018;10(2):57. Crossref
Beg S, Swain S, Hasan H, Barkat MA, Hussain MS. Systematic Review of Herbals as Potential Anti-inflammatory Agents: Recent Advances, Current Clinical Status and Future Perspectives. Pharmacogn Rev. 2011;5(10):120-137. Crossref
Guo C, Wang J, Cao F, Lee RJ, Zhai G. Lyotropic Liquid Crystal Systems in Drug Delivery. Drug Discov Today. 2010;15(23–24):1032–1040. Crossref
Khan N, Kalam MA, Alam MT, Haq SAU, Showket W, Dar ZA, et al. Drug Standardization through Pharmacognostic Approaches and Estimation of Anticancer Potential of Chamomile (Matricaria chamomilla L.) using Prostate-Cancer Cell Lines: An In-vitro Study. J Cancer. 2023;14(3):490–504. Crossref
Petkova N, Ivanov I, Mihaylova D, Lante A. Effect of Pressure Liquid Extraction and Ultrasonic Irradiation Frequency on Inulin, Phenolic Content and Antioxidant Activity in Burdock (Arctium lappa L.) Roots. Acta Scientiarum Polonorum Hortorum Cultus. 2020;19(3):125–133. Crossref
Emilia I, Setiawan A, Novianti D, Mutiara D, Rangga. Skrining FItokimia Ekstrak Daun Sungkai (Peronema canescens Jack.) secara Infundansi dan Maserasi. Jurnal Indobiosains. 2023;5(2):95–102. Crossref
Nabila, Sumaiyah, Salim E. Dried Samples Characterization and Determination of Total Phenol and Flavonoid of Ethanol Extract from Musa paradisiaca l. Fruit Peel. World Journal of Advanced Research and Reviews. 2022;16(3):941-946. Crossref
Ramadhan H, Forestryana D, Jamaludin W Bin, Palguno SK. Antibacterial Activity of Liquid Crystal Nanoparticles Gel of Binjai Leaves Methanol Extract (Mangifera caesia Jack. Ex. Wall.) Against Propionibacterium Acnes. International Journal of Applied Pharmaceutics. 2022;14(5):67–71. Crossref
Zulfa E, Novianto D, Setiawan D. Formulasi Nanoemulsi Natrium Diklofenak dengan Variasi Kombinasi Tween 80 Dan Span 80: Kajian Karakteristik Fisik Sediaan. Media Farmasi Indonesia. 2019;14(1):1471-1477. Crossref
Sun X, Pan C, Ying Z, Yu D, Duan X, Huang F, et al. Stabilization of Zein Nanoparticles with K-Carrageenan and Tween 80 for Encapsulation of Curcumin. Int J Biol Macromol. 2020;146:549–559. Crossref
Akib NI, Hendra NS, Purnama Putri AE, Armadhani I, Tendri Adjeng AN, Mahmudah R. Preparation of Phytosome of Kersen Leaves (Muntingia calabura L.) Ethanol Extract as Antioxidant. Jurnal Farmasi Sains dan Praktis. 2021;7(3):393–404. Crossref
Farida Y, Rahmat D, Amanda AW. Anti-Inflammation Activity Test of Nanoparticles Ethanol Extract of Temulawak Rhizome (Curcuma xanthorrhiza Roxb.) with Protein Denaturation Inhibition Method. Jurnal Ilmu Kefarmasian Indonesia. 2018;16(2):225-230. Crossref
Silvestrini AVP, Garcia Praça F, Leite MN, de Abreu Fantini MC, Frade MAC, Badra Bentley MVL. Liquid Crystalline Nanoparticles Enable a Multifunctional Approach for Topical Psoriasis Therapy by Co-delivering Triptolide and siRNAs. Int J Pharm. 2023;640. Crossref
Ball R, Bajaj P, Whitehead KA. Achieving Long-term Stability of Lipid Nanoparticles: Examining the Effect of pH, Temperature, and Lyophilization. Int J Nanomedicine. 2016;12:305–315. Crossref
Supraba W, Juliantoni Y, Ananto AD. The Effect of Stirring Speeds to the Entrapment Efficiency in a Nanoparticles Formulation of Java Plum's Seed Ethanol Extract (Syzygium cumini). Acta Chimica Asiana. 2021;4(1):197–202. Crossref
Ramadhan H, Helmina R, Fahriana Y, Muthia R, Fitryanti, Forestryana D. Formulasi Gel Ekstrak Metanol Daun Balik Angin (Alphitonia incana (Roxb.) Teijsm. & Binn. Ex Kurz). Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2024;11(2):98–113. Crossref
Ma Q, Jiang JG, Yuan X, Qiu K, Zhu W. Comparative Antitumor and Anti-inflammatory Effects of Flavonoids, Saponins, Polysaccharides, Essential Oil, Coumarin and Alkaloids from Cirsium japonicum DC. Food and Chemical Toxicology. 2019;125:422–429. Crossref
Shabir S, Yousuf S, Singh SK, Vamanu E, Singh MP. Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: an Attenuation of Cellular, Biochemical, and Organismal Markers. Antioxidants. 2022;11(8):1623. Crossref
Tao Y, Wu D, Zhang QA, Sun DW. Ultrasound-assisted Extraction of Phenolics from Wine Lees: Modeling, Optimization and Stability of Extracts during Storage. Ultrason Sonochem. 2014;21(2):706–715. Crossref
Yousefbeyk F, Hemmati G, Gholipour Z, Ghasemi S, Evazalipour M, Schubert C, et al. Phytochemical Analysis, Antioxidant, Cytotoxic, and Antimicrobial Activities of Golden Chamomile (Matricaria Aurea (Loefl.) Schultz Bip). Zeitschrift für Naturforschung C. 2022;77(7–8):331–342. Crossref
Sah A, Naseef PP, Kuruniyan MS, Jain GK, Zakir F, Aggarwal G. A Comprehensive Study of Therapeutic Applications of Chamomile. Pharmaceuticals. 2022;15(10). Crossref
Andriani R, Malaka MH, Jubir I, Aspadiah V, Fristiohady A. Review Jurnal: Pemanfaatan Etosom Sebagai Bentuk Sediaan Patch. Farmasains : Jurnal Ilmiah Ilmu Kefarmasian. 2021;8(1):45–57. Crossref
Sharma RK, Ganesan P, Tyagi V, Metselaar H, Sandaran SC. Thermal Properties and Heat Storage Analysis of Palmitic Acid-TiO2 Composite as Nano-Enhanced Organic Phase Change Material (NEOPCM). Appl Therm Eng. 2016;99:1254–1262. Crossref
Zhai J, Fong C, Tran N, Drummond CJ. Non-Lamellar Lyotropic Liquid Crystalline Lipid Nanoparticles for the Next Generation of Nanomedicine. ACS Nano. 2019;13(6):6178–6206. Crossref
Mursal ILP, Fajriyani A, Nurfirzatulloh I, Insani M, Shafira RA. Jenis-Jenis dan Ukuran Nanopartikel dalam Sistem Penghantaran Obat yang Baik : Literature Review Articel. Jurnal Ilmiah Wahana Pendidikan. 2023;16(9):457–462. Crossref
Rahmawanty D, Anwar E, Bahtiar A. Utilization of Chitosan Cross-Linked with Tripolyphosphate as The Excipient of Snakehead Fish (Channa striatus) Gel. Jurnal Ilmu Kefarmasian Indonesia. 2015;13(1):76–81. Crossref
Juliantoni Y, Hajrin W, Subaidah WA. Nanoparticle Formula Optimization of Juwet Seeds Extract (Syzygium cumini) using Simplex Lattice Design Method. Jurnal Biologi Tropis. 2020;20(3):416–422. Crossref
Patel PJ, Gohel MC, Acharya SR. Exploration of Statistical Experimental Design to Improve Entrapment Efficiency of Acyclovir in Poly (d, l) Lactide Nanoparticles. Pharm Dev Technol. 2014;19(2):200–212. Crossref
Ganesan P, Ramalingam P, Karthivashan G, Ko YT, Choi DK. Recent Developments in Solid Lipid Nanoparticle and Surface-Modified Solid Lipid Nanoparticle Delivery Systems for Oral Delivery of Phyto-Bioactive Compounds in Various Chronic Diseases. Int J Nanomedicine. 2018;13:1569–1583. Crossref
Jaiswal P, Gidwani B, Vyas A. Nanostructured Lipid Carriers and Their Current Application in Targeted Drug Delivery. Artif Cells Nanomed Biotechnol. 2016;44(1):27–40. Crossref
Benedini L, Placente D, Ruso J, Messina P. Adsorption/Desorption Study of Antibiotic and Anti-inflammatory Drugs Onto Bioactive Hydroxyapatite Nano-Rods. Mater Sci Eng C. 2019;99:180–190. Crossref
Alnuqaydan AM, Almutary AG, Azam M, Manandhar B, De Rubis G, Madheswaran T, et al. Phytantriol-Based Berberine-Loaded Liquid Crystalline Nanoparticles Attenuate Inflammation and Oxidative Stress in Lipopolysaccharide-Induced RAW264.7 Macrophages. Nanomaterials. 2022;12(23):4312. Crossref
Authors
Widyan Muchzadi Akbar, Muhammad Dzakwan and Fransiska Leviana (2025) “Development of Chamomile Lyotropic Liquid Crystal Nanoparticle: Anti-Inflammatory Potential”, Farmasains : Jurnal Ilmiah Ilmu Kefarmasian, 12(1), pp. 34–47. doi: 10.22236/farmasains.v12i1.17402.
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