White Mugwort (Artemisia lactiflora) Fraction-Loaded Chitosan Nanoparticles: Formulation and Optimization using Box-Behnken Design
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Abstract
White mugwort (Artemisia lactiflora) contains active substances such as steroids (sitosterol, stigmasterol), essential oils, furanocoumarins, and vitamins. Stigmasterol may act as an aphrodisiac, but has poor water solubility, which limits its bioavailability. Particle size reduction is a strategy used to improve the oral bioavailability of pharmaceuticals by creating nanoparticles. This study aimed to obtain optimal formulation of white mugwort nanoparticles (WMN) via ionic gelation approach with chitosan polymer and sodium tripolyphosphate (Na-TPP) using Box-Behnken Design (BBD) methodology. Independent variables such as polymer, surfactant (tween 80), and agitation speed were used in this optimization. The dependent variables employed were particle size, polydispersity index (PDI), and entrapment efficiency (EE). The ideal formula was evaluated using Fourier Transform Infra-Red (FTIR-ATR) spectroscopic analysis, Transmission Electron Microscopy (TEM), and in vitro release testing using simulated gastric fluid at pH 1.2. The data were subjected to statistical analysis via analysis of variance (ANOVA). The optimal formulation of WMN was achieved with 50 mL chitosan 0.1%, 0.1 g tween 80, and a stirring speed of 1000 rpm. The optimal formula exhibited a particle size of 128.73 ± 0.939 nm, a PDI of 0.807 ± 0.042, and an EE of 92.194 ± 1.273%. WMN have spherical shape and can enhance drug release in vitro relative to the white mugwort fraction prior to formulation, so it is anticipated that the bioavailability of stigmasterol - a major component of white mugwort will improve when incorporated into nanoparticles.
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1.Rusmin D. The Development of Pruatjan (Pimpinella pruatjan Molk.) Cultivation as A Medicinal Crops. Perspektif. 2017; 16(2):80 doi:10.21082/PSP.V16N2.2017.80-93
2.Aji AP, Septianingsih R, Indratmoko S, Y AN, Indriana L. Enhancement of Aphrodisiac Activity of Icariin Microemulsion, Purwaceng Extract and Pasak Bumi Extract. J Tumbuhan Obat Indonesia. 2024; 17(1):44-55. doi:10.31002/jtoi.v17i1.984
3.Palanichamy C, Pavadai P, Panneerselvam T, Arunachalam S, Babkiewicz E, Pandian SRK, Jeyarajaguru KS, Ammunje DN, Kannan S, Chandrasekaran J, Sundar K, Maszczyk P, Kunjiappan S. Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach. Molecules. 2022; 27(12):3799 doi:10.3390/ MOLECULES27123799/S1
4.Abdullah SS, Putra PP, Antasionasti I, Rundengan G, Suoth EJ, Abdullah RPI, Abdullah F. Analysis of Physicochemical, Pharmacokinetic and Toxicological Properties of Pericarpium of Nutmeg (Myristica fragransa) Using Artificial Intelligence. Chem Prog. 2021; 14(2):81. doi:10.35799/cp.14.2.2021.37112
5.Rahmawati A, Kurniawan D, Damayanti DS. Stigmasterol from Cowpea Seeds (Vigna unguiculata) Has Potential as a Cholesterol Absorption Inhibitor through NPC1L1 Inhibition and ABCG5 Activation: An In Silico Study. J Bio Kompl Med. 2023; 10(1):1-12.
6.Patel AA, Patel RJ, Mishra P. Nanosuspension for oral delivery of tadalafil: Pharmacodynamic and pharmacokinetic studies. J Drug Deliv Sci Technol. 2020; 61(4):102203 doi:10.1016/J.JDDS T.2020.102203
7.Fahmy UA and Aljaeid BM. Tadalafil transdermal delivery with alpha-lipoic acid self nanoemulsion for treatment of erectile dysfunction by diabetes mellitus. Int J Pharmacol. 2018; 14(7):945-951. doi:10.3923/ijp.2018.945.951
8.Gardouh AR, Elhusseiny S, Gad S. Mixed Avanafil and Dapoxetin Hydrochloride cyclodextrin nano-sponges: Preparation, In-vitro characterization, and bioavailability determination. J Drug Deliv Sci Technol. 2022; 68(10):103100 doi:10.1016/J.JDDST.2022.103100
9.Kesharwani R, Patel DK, Yadav PK. Bioavailability Enhancement Of Repaglinide Using Nano Lipid Carrier: Preparation Characterization And In Vivo Evaluation. Int J Appl Pharm. 2022; 14(5):181-189. doi:10.22159/IJAP.2022V14I5.45032
10.Ikhsas Y, Kusmardi K, Kodariah R, Kamilah F. The Effect of Pomegranate Peel (Punica granatum L.) Extract in Chitosan Nanoparticle on the Macrophage Polarization in DSS-Induced Mice. Trop J of Nat Prod Res. 2025; 9(2):636-641. doi:10.26538/TJNPR/V9I2.27
11.Koroleva MY, Yurtov EV, Piri F, Afarani S, Masoud A, Tasso G, Machado P, Veleirinho MB, Aparecida L, Sukmawati A, Utami W, Yuliani R, Da'i M, Nafarin A. Effect of tween 80 on nanoparticle preparation of modified chitosan for targeted delivery of combination doxorubicin and curcumin analogue. IOP Conf Ser Mater Sci Eng. 2018; 311(1):012024 doi:10.1088/1757-899X/311/1/012024
12.Rahaiee S, Shojaosadati SA, Hashemi M. An efficient ionic gelation based nano-delivery system to improve the stability and controlled release of saffron extracts. Biocatal Agric Biotechnol. 2023; 52(12):102831. doi:10.1016/J.BCAB.2023.102831
13.Nuria MC, Pujaka AE, Safitri EI. Antibacterial Activity of Ethanol Extract of Portulaca oleracea L. Herb from Various Extraction Methods Against Salmonella typhimurium. Microbiol Indones. 2021;15(4):139-144.
14.Peratiwi SG, Tahara N, Mustikawati1 B, Maisyarah IT, Indradi RB, Barliana MI. Phytochemical Screening and TLC Profiles of Extract and Fractions of. Indones J Biol Pharm. 2023; 3(1):10-18.
15.Onugwu AL, Attama AA, Nnamani PO, Onugwu SO, Onuigbo EB, Khutoryanskiy V V. Development and optimization of solid lipid nanoparticles coated with chitosan and poly(2-ethyl-2-oxazoline) for ocular drug delivery of ciprofloxacin. J Drug Deliv Sci Technol. 2022; 74(9):103527 doi:10.1016/j.jddst.2022.103527
16.Ilgü H, Turan T, Şanli-Mohamed G. Preparation, characterization and optimization of chitosan nanoparticles as carrier for immobilization of thermophilic recombinant esterase. J Macromol Sci Part A: Pure Appl Chem. 2011; 48(9):713-721. doi:10.1080/10601325.201 1.596050
17.Sheweita SA, Alian DME, Haroun M, Nounou MI, Patel A, El-Khordagui L. Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats. Oxid Med Cell Longev. 2023; 1-16 doi:10.1155/2023/9944985
18.Gutiérrez-Ruíz SC, Cortes H, González-Torres M, Almarhoon ZM, Sönmez Gürer E, Sharifi-Rad J, Leyva-Gómez G. Optimize the parameters for the synthesis by the ionic gelation technique, purification, and freeze-drying of chitosan-sodium tripolyphosphate nanoparticles for biomedical purposes. J Biol Eng. 2024; 18(1):1-16. doi:10.1186/S13036-024-00403-W/FIGURES/7
19.Jiang T, Wang Y, Yu Z, Du L. Synthesis, characterization of chitosan/tripolyphosphate nanoparticles loaded with 4-chloro-2-methylphenoxyacetate sodium salt and its herbicidal activity against Bidens pilosa L. Sci Rep. 2024; 14(1):1-12. doi:10.1038/s41598-024-69438-9
20.Pandya J. Development and validation of HPLC methods for the standardization of Stigmasterol & Lupeol from the extract of Butea monosperma (Lam) and it’s formulation. J Pharmacogn Phytochem. 2019; 8(3):729-741.
21.Owczarek M, Herczyńska L, Sitarek P, Lucyna, Kowalczyk, T, Synowiec, E, Krucińska, I. Chitosan Nanoparticles-Preparation, Characterization and Their Combination with Ginkgo biloba Extract in Preliminary In Vitro Studies. Molecules. 2023; 28(13):4950. doi:10.3390/MOLECULES28134950/S1.
22.Asfour HZ, Alhakamy NA, Fahmy UA, Ahmed OAA, Rizg WY, Felimban RI, Abdel-Naim AB, Abourehab MAS, Mansouri RA, Omar UM, Badr-Eldin SM. Zein-Stabilized Nanospheres as Nanocarriers for Boosting the Aphrodisiac Activity of Icariin: Response Surface Optimization and In Vivo Assessment. Pharmaceutics. 2022; 14(6):1279. doi:10.3390/pharmaceutics 14061279
23.Zhang S and Wang C. Precise Analysis of Nanoparticle Size Distribution in TEM Image. Methods Protoc. 2023; 6(4):63. doi:10.3390/MPS6040063
24.Sohn JS and Choi JS. Development of a tadalafil transdermal formulation and evaluation of its ability to in vitro transdermal permeate using Strat-M® membrane. Eur J Pharm Sci. 2024; 192(106615):1-9. doi:10.1016/j.ejps.2023.106615
25.Jakobek L, Strelec I, Kenjerić D, Šoher L, Tomac I, Matić P. Simulated Gastric and Intestinal Fluid Electrolyte Solutions as an Environment for the Adsorption of Apple Polyphenols onto β-Glucan. Molecules. 2022; 27(19):6683. doi:10.3390/MOLECULES 27196683/S1
26.Amenaghawon AN, Salokun O, Okhonmina JO, Egharevba IP. Determination of optimum composition of fermentation medium for citric acid production from watermelon rinds using response surface methodology. Trop J Nat Prod Res. 2017; 1(1):12-16. doi:10.26538/TJNPR/V1I1.3
27.Setiawan A, Kiromah NZW, Widiastuti TC. Formulation and Evaluation of Nanoparticle Tablet Preparations of Bay Leaf Extract (Syzygium polyanthum) with Variations in Concentration of Na Alginate and Avicel PH 102. Pharmacon: J Farm Indonesia. 2020; 17(1):24-30. doi:10.23917/pharmacon.v17i1.10107
28.Van Bavel N, Issler T, Pang L, Anikovskiy M, Prenner EJ. A Simple Method for Synthesis of Chitosan Nanoparticles with Ionic Gelation and Homogenization. Molecules. 2023; 28(11):4328. doi:10.3390/MOLECULES28114328
29.Hidayati EN, Rahayyu AM, Azzahra F. Physical Characterization of Chitosan-based Syzygium polyanthum Leaves Extract Nanoparticles Dyslipidemia is a metabolic disorder characterized by an increase in Low-Densi. Pharmacon: J Farm Indonesia. 2023; 20(2):120-128.
30.Saryanti D, Dai M, Cabral KB, Wikantyasning ER. Applications Of Synthetic And Herbal Nanoparticles As Aphrodisiacs: A Systematic Review. Int J Appl Pharmaceut. 2024; 16(5):25-30. doi:10.22159/IJAP.2024V16S5.52467
31.Sreekumar S, Goycoolea FM, Moerschbacher BM, Rivera-Rodriguez GR. Parameters influencing the size of chitosan-TPP nano- and microparticles. Sci Rep. 2018; 8(1):4695. doi:10.1038/S41598-018-23064-4.
32.Gonçalves C, Ferreira N, Lourenço L. Production of Low Molecular Weight Chitosan and Chitooligosaccharides (COS): A Review. Polymers (Basel). 2021; 13(15):2466. doi:10.3390/POLYM 13152466.
33.Bhattacharya S. Central Composite Design for Response Surface Methodology and Its Application in Pharmacy. IntechOpen; 2021. 1-19 p. doi:10.5772/INTECHOPEN.95835.
34.LaPanse AJ, Krishnan A, Posewitz MC. Adaptive Laboratory Evolution for algal strain improvement: methodologies and applications. Algal Res. 2021; 53:102122 doi:10.1016/j.algal.202 0.102122.
35.Pan C, Qian J, Fan J, Guo, H, Gou, L, Yang, H, Liang, C. Preparation nanoparticle by ionic cross-linked emulsified chitosan and its antibacterial activity. Colloids Surf A Physicochem Eng Asp. 2019; 568:362-370. doi:10.1016/J.COLSURFA.2019.02.039
36.Saryanti D, Nugraheni D, Astuti NS. Preparation and Characterization of Betel Leaves (Piper betle Linn) Extract Nanoparticle with Ionic Gelation Method. J Trop Pharm Chem. 2020; 5(1):15-20. doi:10.25026/JTPC.V5I1.224.
37.Saifi Z, Ralli T, Rizwanullah M, Alam, M, Vohora, D, Mir, SR, Amin, S, Ameen, S. BBD Driven Fabrication of Hydroxyapatite Engineered Risedronate Loaded Thiolated Chitosan Nanoparticles and Their In Silico, In Vitro, and Ex Vivo Studies. Micromachines. 2023; 14(12):2182. doi:10.3390/MI14122182.
38.Annisa R, Lestari RI, Aqila SS, Fanany, CT, Fitrianingsih, AA, Rachmawati, E, Rahmadiani, N, Muti’ah, R. Optimization and Characterization of Dayak Onion (Eleutherine palmifolia (L.) Merr) Extract Nanoparticles Using Cross-link Method: J Nat Prod Res. 2025; 9(2):480-486. doi:10.26538/TJNPR/V9I2.10.
39.Yurtdaş Kirimlioğlu G and Öztürk AA. Levocetirizine Dihydrochloride-Loaded Chitosan Nanoparticles: Formulation and In Vitro Evaluation. Turk J Pharm Sci. 2020; 17(1):27-35. doi:10.4274/TJPS.GALENOS.2018.34392
40.Sharaf NS, Shetta A, Elhalawani JE, Mamdouh W. Applying Box–Behnken Design for Formulation and Optimization of PLGA-Coffee Nanoparticles and Detecting Enhanced Antioxidant and Anticancer Activities. Polymers (Basel). 2022; 14(1):144 doi:10.3390/POLYM14010144