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Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Preparation, Physicochemical Characterization, and Stability Study of Lippia origanoides Essential Oil-based Nanoemulsion as a Topical Delivery System

Author(s): Carlos Andrés Benitez-Llano, Oscar Albeiro Florez-Acosta*, Darsy Dayana Velasquez-Polo, Ana Cecilia Mesa-Arango and Carolina Zapata-Zapata

Volume 12, Issue 3, 2024

Published on: 14 September, 2023

Page: [251 - 261] Pages: 11

DOI: 10.2174/2211738511666230815155614

Price: $65

Abstract

Introduction: Fungal diseases are a priority in research, development, and health care, according to the WHO, mainly due to Candida spp. Essential oils (EOs) of the genus Lippia have demonstrated broad antimicrobial biological activity. Previous studies identified the anti-Candida potential of a thymol/p-cymene chemotype EO from Lippia origanoides H.B.K coded “0018”. Nanoemulsions favor the biological activity of EOs and overcome limitations such as low solubility, instability against oxidizing agents, pH, light, and low permeability. To develop, characterize, and adjust a prototype of an O/W nanoemulsion containing the "0018” EO from Lippia origanoides for its evaluation in an in vitro permeability study.

Methods: Nanoemulsions were obtained using a high energy high shear method. Their particle size distribution, Z potential, viscosity, pH, encapsulation efficiency (EE), thermodynamic stability and the Turbiscan Stability Index (TSI) were evaluated. The nanoemulsion prototype was adjusted to improve performance characteristics and microbiological efficacy. Thymol was used as an analyte in the EO quantification using UHPLC-DAD.

Results: An O/W nanoemulsion with hydrodynamic diameter <200 nm and polydispersity index <0.3, EE >95%, with TSI < 1.5, anti-Candida albicans efficiency >95% was obtained; permeable with a flow of 6.0264 μg/cm2/h and permeability coefficient of 1.3170x10-3 cm/h.

Conclusion: A pharmaceutical formulation prototype is obtained that maintains the physical and physicochemical characteristics over time. Permeability is verified in an in-vitro model. It is proposed to evaluate its antifungal activity in preclinical or clinical studies as a contribution to the treatment of topical fungal diseases caused by Candida spp., through the use of biological resources and Colombian biodiversity.

Graphical Abstract

[1]
World Health Organization. WHO fungal priority pathogens list to guide research, development and public health action. 2022. Available from: https://www.who.int/publications/i/item/9789240060241
[2]
McCarty TP, White CM, Pappas PG. Candidemia and invasive candidiasis. Infect Dis Clin North Am 2021; 35(2): 389-413.
[http://dx.doi.org/10.1016/j.idc.2021.03.007] [PMID: 34016283]
[3]
Sasani E, Rafat Z, Ashrafi K, et al. Vulvovaginal candidiasis in Iran: A systematic review and meta-analysis on the epidemiology, clinical manifestations, demographic characteristics, risk factors, etiologic agents and laboratory diagnosis. Microb Pathog 2021; 154: 104802.
[http://dx.doi.org/10.1016/j.micpath.2021.104802] [PMID: 33741400]
[4]
Abdallah NA, Said M, Mahmoud MT, Omar MA. Onychomycosis: Correlation between the dermoscopic patterns and fungal culture. J Cosmet Dermatol 2020; 19(5): 1196-204.
[http://dx.doi.org/10.1111/jocd.13144] [PMID: 31502751]
[5]
Piraccini BM, Starace M, Rubin AI, Di Chiacchio NG, Iorizzo M, Rigopoulos D. Onychomycosis: Recommendations for diagnosis, assessment of treatment efficacy, and specialist referral. The consonance consensus Project. Dermatol Ther 2022; 12(4): 885-98.
[http://dx.doi.org/10.1007/s13555-022-00698-x] [PMID: 35262878]
[6]
Gugnani HC, Paliwal-Joshi A, Rahman H, et al. Occurrence of pathogenic fungi in soil of burrows of rats and of other sites in bamboo plantations in India and Nepal. Mycoses 2007; 50(6): 507-11.
[http://dx.doi.org/10.1111/j.1439-0507.2007.01402.x] [PMID: 17944715]
[7]
A comparison of the different questionnaires used to measure health-related quality of life in patients with dermatological conditions. Br J Dermatol 2022; 186(3): e111-33.
[PMID: 35254681]
[8]
Vaseghi N, Sharifisooraki J, Khodadadi H, et al. Global prevalence and subgroup analyses of coronavirus disease (COVID ‐19) associated Candida auris infections (CACa): A systematic review and meta‐analysis. Mycoses 2022; 65(7): 683-703.
[http://dx.doi.org/10.1111/myc.13471] [PMID: 35555921]
[9]
Atiencia-Carrera MB, Cabezas-Mera FS, Tejera E, Machado A. Prevalence of biofilms in Candida spp. bloodstream infections: A meta-analysis. PLoS One 2022; 17(2): e0263522.
[http://dx.doi.org/10.1371/journal.pone.0263522] [PMID: 35113972]
[10]
Vinayagamoorthy K, Pentapati KC, Prakash H. Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID‐19) patients: A systematic review. Mycoses 2022; 65(6): 613-24.
[http://dx.doi.org/10.1111/myc.13447] [PMID: 35441748]
[11]
Kesraoui S, Andrés MF, Berrocal-Lobo M, Soudani S, Gonzalez-Coloma A. Direct and indirect effects of essential oils for sustainable crop protection. Plants 2022; 11(16): 2144.
[http://dx.doi.org/10.3390/plants11162144]
[12]
Hou T, Sana SS, Li H, et al. Essential oils and its antibacterial, antifungal and anti-oxidant activity applications: A review. Food Biosci 2022; 47: 101716.
[http://dx.doi.org/10.1016/j.fbio.2022.101716]
[13]
Gómez-Sequeda N, Cáceres M, Stashenko EE, Hidalgo W, Ortiz C. Antimicrobial and antibiofilm activities of essential oils against Escherichia coli O157:H7 and Methicillin-Resistant Staphylococcus aureus (MRSA). Antibiotics 2020; 9(11): 730.
[http://dx.doi.org/10.3390/antibiotics9110730] [PMID: 33114324]
[14]
de Melo ARB, Maciel Higino TM, da Rocha Oliveira ADP, et al. Lippia sidoides and Lippia origanoides essential oils affect the viability, motility and ultrastructure of Trypanosoma cruzi. Micron 2020; 129: 102781.
[http://dx.doi.org/10.1016/j.micron.2019.102781] [PMID: 31830667]
[15]
Guillín Y, Cáceres M, Torres R, Stashenko E, Ortiz C. Effect of essential oils on the inhibition of biofilm and quorum sensing in Salmonella enteritidis 13076 and Salmonella typhimurium 14028. Antibiotics 2021; 10(10): 1191.
[16]
Hernandes C, Pina ES, Taleb-Contini SH, et al. Lippia origanoides essential oil: An efficient and safe alternative to preserve food, cosmetic and pharmaceutical products. J Appl Microbiol 2017; 122(4): 900-10.
[http://dx.doi.org/10.1111/jam.13398] [PMID: 28055127]
[17]
Escobar P, Milena Leal S, Herrera LV, Martinez JR, Stashenko E. Chemical composition and antiprotozoal activities of Colombian Lippia spp essential oils and their major components. Mem Inst Oswaldo Cruz 2010; 105(2): 184-90.
[http://dx.doi.org/10.1590/S0074-02762010000200013] [PMID: 20428679]
[18]
Cunha C, Ribeiro HM, Rodrigues M, Araujo ARTS. Essential oils used in dermocosmetics: Review about its biological activities. J Cosmet Dermatol 2022; 21(2): 513-29.
[http://dx.doi.org/10.1111/jocd.14652] [PMID: 34871468]
[19]
Ferreira de Oliveira D, Andrade Martins J, Souza e Costa J, Rocha Oliveira C. Skin phytotherapy and pharmacological aspects: A brief review. Br J Natural Sci 2022; 4(3)
[http://dx.doi.org/10.31415/bjns.v4i3.163]
[20]
Souto EB, Cano A, Martins-Gomes C, Coutinho TE, Zielińska A, Silva AM. Microemulsions and nanoemulsions in skin drug delivery. Bioengineering 2022; 9(4): 158.
[http://dx.doi.org/10.3390/bioengineering9040158]
[21]
Lv X, Liu T, Ma H, et al. Preparation of essential oil-based microemulsions for improving the solubility, ph stability, photostability, and skin permeation of quercetin. AAPS PharmSciTech 2017; 18(8): 3097-104.
[http://dx.doi.org/10.1208/s12249-017-0798-x] [PMID: 28516411]
[22]
Cecchini ME, Paoloni C, Campra N, et al. Nanoemulsion of Minthostachys verticillata essential oil. In-vitro evaluation of its antibacterial activity. Heliyon 2021; 7(1): e05896.
[http://dx.doi.org/10.1016/j.heliyon.2021.e05896] [PMID: 33521347]
[23]
Wilson RJ, Li Y, Yang G, Zhao CX. Nanoemulsions for drug delivery. Particuology 2022; 64: 85-97.
[http://dx.doi.org/10.1016/j.partic.2021.05.009]
[24]
Marzuki NHC, Wahab RA, Hamid MA. An overview of nanoemulsion: Concepts of development and cosmeceutical applications. Biotechnol Biotechnol Equip 2019; 33(1): 779-97.
[http://dx.doi.org/10.1080/13102818.2019.1620124]
[25]
Galindo-Alvarez J, Le KA, Sadtler V, et al. Enhanced stability of nanoemulsions using mixtures of non-ionic surfactant and amphiphilic polyelectrolyte. Colloids Surf A Physicochem Eng Asp 2011; 389(1-3): 237-45.
[http://dx.doi.org/10.1016/j.colsurfa.2011.08.021]
[26]
Lee MS, Yee DW, Kubiak JM, Santos PJ, Macfarlane RJ. Improving nanoparticle superlattice stability with deformable polymer gels. J Chem Phys 2023; 158(6): 064901.
[http://dx.doi.org/10.1063/5.0130800] [PMID: 36792494]
[27]
Wang B, Wang L, Li D, Adhikari B, Shi J. Effect of gum Arabic on stability of oil-in-water emulsion stabilized by flaxseed and soybean protein. Carbohydr Polym 2011; 86(1): 343-51.
[http://dx.doi.org/10.1016/j.carbpol.2011.04.059] [PMID: 34662972]
[28]
Danaei M, Dehghankhold M, Ataei S, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018; 10(2): 57.
[http://dx.doi.org/10.3390/pharmaceutics10020057]
[29]
Yildirim ST, Oztop MH, Soyer Y. Cinnamon oil nanoemulsions by spontaneous emulsification: Formulation, characterization and antimicrobial activity. Lebensm Wiss Technol 2017; 84: 122-8.
[http://dx.doi.org/10.1016/j.lwt.2017.05.041]
[30]
Li J, Chang JW, Saenger M, Deering A. Thymol nanoemulsions formed via spontaneous emulsification: Physical and antimicrobial properties. Food Chem 2017; 232: 191-7.
[http://dx.doi.org/10.1016/j.foodchem.2017.03.147] [PMID: 28490064]
[31]
Asbahani AE, Miladi K, Badri W, et al. Essential oils: From extraction to encapsulation. Int J Pharm 2015; 483(1-2): 220-43.
[http://dx.doi.org/10.1016/j.ijpharm.2014.12.069] [PMID: 25683145]
[32]
Lin L, Zhu Y, Thangaraj B, Abdel-Samie MAS, Cui H. Improving the stability of thyme essential oil solid liposome by using β-cyclodextrin as a cryoprotectant. Carbohydr Polym 2018; 188: 243-51.
[http://dx.doi.org/10.1016/j.carbpol.2018.02.010] [PMID: 29525162]
[33]
Sotelo-Boyás M, Correa-Pacheco Z, Bautista-Baños S, Gómez Y, Gómez Y. Release study and inhibitory activity of thyme essential oil-loaded chitosan nanoparticles and nanocapsules against foodborne bacteria. Int J Biol Macromol 2017; 103: 409-14.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.063] [PMID: 28526346]
[34]
Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: An advanced mode of drug delivery system. 3 Biotech 2015; 5(2): 123-7.
[http://dx.doi.org/10.1007/s13205-014-0214-0] [PMID: 28324579]
[35]
Majeed A, Roy PSD, Sharma N, et al. Nanoemulsions: Applications, challenges and future perspectives. Indian J Agric Biochem 2021; 34(2): 107-15.
[http://dx.doi.org/10.5958/0974-4479.2021.00015.0]
[36]
Aswathanarayan JB, Vittal RR. Nanoemulsions and their potential applications in food industry. Front Sustain Food Syst 2019; 3: 95.
[http://dx.doi.org/10.3389/fsufs.2019.00095]
[37]
Ugur Kaplan AB, Cetin M, Orgul D, Taghizadehghalehjoughi A, Hacımuftuoglu A, Hekimoglu S. Formulation and in vitro evaluation of topical nanoemulsion and nanoemulsion-based gels containing daidzein. J Drug Deliv Sci Technol 2019; 52: 189-203.
[http://dx.doi.org/10.1016/j.jddst.2019.04.027]
[38]
Guzmán C, Rojas MA, Aragón M. Optimization of ultrasound-assisted emulsification of emollient nanoemulsions of seed oil of Passiflora edulis var. edulis. Cosmetics 2021; 8(1): 1.
[39]
Benjemaa M, Neves MA, Falleh H, Isoda H, Ksouri R, Nakajima M. Nanoencapsulation of Thymus capitatus essential oil: Formulation process, physical stability characterization and antibacterial efficiency monitoring. Ind Crops Prod 2018; 113: 414-21.
[http://dx.doi.org/10.1016/j.indcrop.2018.01.062]
[40]
Liu Q, Gao Y, Fu X, et al. Preparation of peppermint oil nanoemulsions: Investigation of stability, antibacterial mechanism and apoptosis effects. Colloids Surf B Biointerfaces 2021; 201: 111626.
[http://dx.doi.org/10.1016/j.colsurfb.2021.111626] [PMID: 33631642]
[41]
Trujillo-Cayado LA, Santos J, Calero N, Alfaro-Rodríguez MC, Muñoz J. Strategies for reducing Ostwald ripening phenomenon in nanoemulsions based on thyme essential oil. J Sci Food Agric 2020; 100(4): 1671-7.
[http://dx.doi.org/10.1002/jsfa.10181] [PMID: 31802496]
[42]
Shin J, Na K, Shin S, Seo SM, Youn HJ, Park IK. Biological activity of thyme white essential oil stabilized by cellulose nanocrystals. Biomolecules 2019; 9(12): 799.
[http://dx.doi.org/10.3390/biom9120799]
[43]
Bazylińska U. Rationally designed double emulsion process for co-encapsulation of hybrid cargo in stealth nanocarriers. Colloids Surf A Physicochem Eng Asp 2017; 532: 476-82.
[http://dx.doi.org/10.1016/j.colsurfa.2017.04.027]
[44]
Cichońska P, Domian E, Ziarno M. Application of optical and rheological techniques in quality and storage assessment of the newly developed colloidal-suspension products: Yogurt-type bean-based beverages. Sensors 2022; 22(21): 8348.
[http://dx.doi.org/10.3390/s22218348] [PMID: 36366047]
[45]
Li M, Kang W, Li Z, et al. Stability of oil-in-water (O/W) nanoemulsions and its oil washing performance for enhanced oil recovery. Phys Fluids 2021; 33(7): 072002.
[http://dx.doi.org/10.1063/5.0058759]
[46]
Arce FJ, Asano N, See GL, Itakura S, Todo H, Sugibayashi K. Usefulness of artificial membrane, strat-m®, in the assessment of drug permeation from complex vehicles in finite dose conditions. Pharmaceutics 2020; 12(2): 173.
[47]
Špaglová M, Papadakos M, Čuchorová M, Matušová D. Release of tretinoin solubilized in microemulsion from carbopol and xanthan gel: In vitro versus ex vivo permeation study. Polymers 2023; 15(2): 329.
[48]
Lee JY, Lee SH, Hwangbo SA, Lee TG. A comparison of gelling agents for stable, surfactant-free oil-in-water emulsions. Materials 2022; 15(18): 6462.
[http://dx.doi.org/10.3390/ma15186462] [PMID: 36143772]
[49]
Zapata-Zapata C, Loaiza-Oliva M, Martínez-Pabón MC, Stashenko EE, Mesa-Arango AC. In vitro activity of essential oils distilled from colombian plants against candidaauris and other candida species with different antifungal susceptibility profiles. Molecules 2022; 27(20): 6837.
[http://dx.doi.org/10.3390/molecules27206837] [PMID: 36296428]
[50]
Pratap-Singh A, Guo Y, Lara Ochoa S, Fathordoobady F, Singh A. Optimal ultrasonication process time remains constant for a specific nanoemulsion size reduction system. Sci Rep 2021; 11(1): 9241.
[http://dx.doi.org/10.1038/s41598-021-87642-9]
[51]
Peng F, Ke Y, Lu S, Zhao Y, Hu X, Deng Q. Anion amphiphilic random copolymers and their performance as stabilizers for O/W nanoemulsions. RSC Advances 2019; 9(26): 14692-700.
[http://dx.doi.org/10.1039/C9RA01383K] [PMID: 35516327]
[52]
Application Note : How important is the TSI - TSI scale and correlation with visual observation. 2022. Available from: www.formulaction.com
[53]
Laxmi M, Bhardwaj A, Mehta S, Mehta A. Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether. Artif Cells Nanomed Biotechnol 2015; 43(5): 334-44.
[http://dx.doi.org/10.3109/21691401.2014.887018]
[54]
M27Ed4: Broth Dilution Antifungal Susceptibility, Yeasts. 2023. Available from: https://clsi.org/standards/products/microbiology/documents/m27/
[55]
Kunita R, Nishijima T, Todo H, Sugibayashi K, Sakaguchi H. A mathematical approach using strat-m® to predict the percutaneous absorption of chemicals under finite dose conditions. Pharmaceutics 2022; 14(7): 1370.
[56]
OECD Guidelines for the Testing of Chemicals, Section 4 : Health Effects. In: Test No 428: Skin Absorption: in vitro Method. OECD iLibrary 2004.
[57]
Mahamongkol H, Bellantone RA, Stagni G, Plakogiannis FM. Permeation study of five formulations of alpha-tocopherol acetate through human cadaver skin. J Cosmet Sci 2005; 56(2): 91-103.
[PMID: 15868062]
[58]
Proniuk S, Lerkpulsawad S, Blanchard J. A simplified and rapid high-performance liquid chromatographic assay for ketoprofen in isopropyl myristate. J Chromatogr Sci 1998; 36(10): 495-8.
[http://dx.doi.org/10.1093/chromsci/36.10.495] [PMID: 9789981]
[59]
Karimi-Khorrami N, Radi M, Amiri S, Abedi E, McClements DJ. Fabrication, characterization, and performance of antimicrobial alginate-based films containing thymol-loaded lipid nanoparticles: Comparison of nanoemulsions and nanostructured lipid carriers. Int J Biol Macromol 2022; 207: 801-12.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.03.149] [PMID: 35358573]
[60]
Silva HD, Cerqueira MA, Vicente AA. Influence of surfactant and processing conditions in the stability of oil-in-water nanoemulsions. J Food Eng 2015; 167: 89-98.
[http://dx.doi.org/10.1016/j.jfoodeng.2015.07.037]
[61]
Ali MS, Alam MS, Alam N, Siddiqui MR. Preparation, characterization and stability study of dutasteride loaded nanoemulsion for treatment of benign prostatic hypertrophy. Iran J Pharm Res 2014; 13(4): 1125.
[62]
Kumar A, Dixit CK. 3 - Methods for characterization of nanoparticles.In: Advances in Nanomedicine for the Delivery of Therapeutic Nucleic Acids. Woodhead Publishing 2017; pp. 43-58.
[http://dx.doi.org/10.1016/B978-0-08-100557-6.00003-1]
[63]
Minea AA. A review on electrical conductivity of nanoparticle-enhanced fluids. Nanomaterials 2019; 9(11): 1592.
[64]
Sun Y, Deac A, Zhang GGZ. Assessing physical stability of colloidal dispersions using a turbiscan optical analyzer. Mol Pharm 2019; 16(2): 877-85.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b01194] [PMID: 30609372]
[65]
Semenzato A, Costantini A, Meloni M, Maramaldi G, Meneghin M, Baratto G. Formulating O/W emulsions with plant-based actives: A stability challenge for an effective product. Cosmetics 2018; 5(4): 59.
[66]
Herrera-Rodríguez SE, López-Rivera RJ, García-Márquez E, Estarrón-Espinosa M, Espinosa-Andrews H. Mexican oregano (Lippia graveolens) essential oil-in-water emulsions: Impact of emulsifier type on the antifungal activity of Candida albicans. Food Sci Biotechnol 2018; 28(2): 441-8.
[67]
Simon M, Krause P, Chiappisi L, Noirez L, Gradzielski M. Structural control of polyelectrolyte/microemulsion droplet complexes (PEMECs) with different polyacrylates. Chem Sci 2019; 10(2): 385-97.
[http://dx.doi.org/10.1039/C8SC04013C] [PMID: 30713642]
[68]
Kulawik-Pióro A, Kurpiewska J, Kułaszka A. Rheological and sensory properties of hydrophilic skin protection gels based on polyacrylates. Int J Occup Saf Ergon 2017; 24(1): 129-34.
[69]
Fathi M, Vinceković M, Jurić S, Viskić M, Režek Jambrak A, Donsì F. Food-grade colloidal systems for the delivery of essential oils. Food Rev Int 2019; 37(1): 1-45.
[http://dx.doi.org/10.1080/87559129.2019.1687514]
[70]
Lukić M, Pantelić I, Savić SD. Towards optimal ph of the skin and topical formulations: From the current state of the art to tailored products. Cosmetics 2021; 8(3): 69.
[71]
Murdan S, Milcovich G, Goriparthi GS. An assessment of the human nail plate pH. Skin Pharmacol Physiol 2011; 24(4): 175-81.
[http://dx.doi.org/10.1159/000324055] [PMID: 21325875]
[72]
Liu Y, Wei F, Wang Y, Zhu G. Studies on the formation of bifenthrin oil-in-water nano-emulsions prepared with mixed surfactants. Colloids Surf A Physicochem Eng Asp 2011; 389(1-3): 90-6.
[http://dx.doi.org/10.1016/j.colsurfa.2011.08.045]
[73]
Hasssanzadeh H, Alizadeh M, Rezazad Bari M. Formulation of garlic oil‐in‐water nanoemulsion: Antimicrobial and physicochemical aspects. IET Nanobiotechnol 2018; 12(5): 647-52.
[http://dx.doi.org/10.1049/iet-nbt.2017.0104] [PMID: 30095427]
[74]
Burlatsky SF, Atrazhev VV, Dmitriev DV, et al. Surface tension model for surfactant solutions at the critical micelle concentration. J Colloid Interface Sci 2013; 393(1): 151-60.
[http://dx.doi.org/10.1016/j.jcis.2012.10.020] [PMID: 23153677]
[75]
Kulkarni U, Mahalingam R, Pather I, Li X, Jasti B. Porcine buccal mucosa as in vitro model: Effect of biological and experimental variables. J Pharm Sci 2010; 99(3): 1265-77.
[http://dx.doi.org/10.1002/jps.21907] [PMID: 19739112]
[76]
Nicolazzo JA, Reed BL, Finnin BC. The effect of various in vitro conditions on the permeability characteristics of the buccal mucosa. J Pharm Sci 2003; 92(12): 2399-410.
[http://dx.doi.org/10.1002/jps.10505] [PMID: 14603485]
[77]
Schmitt S, Schaefer U, Sporer F, Reichling J. Comparative study on the in vitro human skin permeation of monoterpenes and phenylpropanoids applied in rose oil and in form of neat single compounds. Pharmazie 2010; 65(2): 102-5.
[PMID: 20225652]
[78]
Tuntiyasawasdikul S, Sripanidkulchai B. Development and clinical trials on anti-inflammatory effect of transdermal patch containing a combination of Kaempferia parviflora and Curcuma longa extracts. J Drug Deliv Sci Technol 2022; 68: 103093.
[http://dx.doi.org/10.1016/j.jddst.2022.103093]

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