RSS-Feed abonnieren
DOI: 10.1055/a-1543-1190
Thymol and Piperine-Loaded Poly(D,L-lactic-co-glycolic acid) Nanoparticles Modulate Inflammatory Mediators and Apoptosis in Murine Macrophages
Funding This work was supported by the Swiss National Foundation through the grant project n ° IZSEZO_180383/1 and the Laboratory of Pharmaceutical Technology, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva.Abstract
This study aimed at preparing and characterizing thymol, eugenol, and piperine-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles and evaluating the effect on inflammatory mediators secretion and apoptosis in Raw 264.7 macrophage cells. Nanoparticles were produced by the solvent evaporation technique. Dynamic light scattering and scanning electron microscopy were used to study the physicochemical characteristics. Raw 264.7 macrophage cells were used as a model for in vitro assays. The 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium assay was used to determine the cytotoxicity of the formulated nanoparticles. An annexin V apoptosis detection kit was used to assess apoptosis. Nitric oxide production was determined using the Griess reagent, and the inflammatory mediators level was evaluated with Th1/Th2 cytokine and fluorometric cyclooxygenase kits. The loaded nanoparticles showed a particle size around 190 nm with a low polydispersity between 0.069 and 0.104 and a zeta potential between–1.2 and–9.5 mV. Reduced cytotoxicity of nanoparticles compared to free molecules against Raw 264.7 macrophage cells was observed and seemed to occur through a mechanism associated with apoptosis. A decrease in cyclooxygenase enzyme activity with an increasing concentration was observed. Both free molecules and nanoparticles showed their capacity to modulate the inflammatory process mostly by inhibiting the investigated inflammatory cytokines. The data presented in this study indicate that thymol and piperine-loaded poly(D,L-lactic-co-glycolic acid nanoparticles could serve as a novel anti-inflammatory colloidal drug delivery system with reduced toxicity. However, further study should be considered to optimize the formulation’s loading capacity and thereby probably enhance their bioactivity in treating inflammatory diseases.
Publikationsverlauf
Eingereicht: 02. März 2021
Eingereicht: 08. Juni 2021
Angenommen: 21. Juni 2021
Artikel online veröffentlicht:
21. September 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2018; 9: 7204-7218
- 2 Gkretsi V, Zacharia LC, Stylianopoulos T. Targeting Inflammation to Improve Tumor Drug Delivery. Trends Cancer 2017; 3: 621-630
- 3 Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 2015; 1: 27-30
- 4 Karimpour M, Feizi MAH, Mahdavi M, Krammer B, Verwanger T, Najafi F, Babaei E. Development of curcumin-loaded gemini surfactant nanoparticles: Synthesis, characterization and evaluation of anticancer activity against human breast cancer cell lines. Phytomedicine 2019; 57: 183-190
- 5 Jiang TA. Health Benefits of Culinary Herbs and Spices. J AOAC Int 2019; 102: 395-411
- 6 Shityakov S, Bigdelian E, Hussein AA, Hussain MB, Tripathi YC, Khan MU, Shariati MA. Phytochemical and pharmacological attributes of piperine: A bioactive ingredient of black pepper. Eur J Med Chem 2019; 176: 149-161
- 7 Derosa G, Maffioli P. Sahebkar A. Piperine and Its Role in Chronic Diseases. Adv Exp Med Biol 2016; 928: 173-184
- 8 Barboza JN, da Silva Maia Bezerra Filho C, Silva RO, Medeiros JVR, de Sousa DP. An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol. Oxid Med Cell Longev 2018; 2018: 3957262
- 9 Meeran MFN, Goyal SN, Suchal K, Sharma C, Patil CR, Ojha SK. Pharmacological Properties, Molecular Mechanisms, and Pharmaceutical Development of Asiatic Acid: A Pentacyclic Triterpenoid of Therapeutic Promise. Front Pharmacol 2018; 9: 892
- 10 Budama-Kilinc Y. Piperine Nanoparticles for Topical Application: Preparation, Characterization, In vitro and In silico Evaluation. ChemistrySelect 2019; 4: 11693-11700
- 11 Zhao K, Li D, Shi C, Ma X, Rong G, Kang H, Wang X, Sun B. Biodegradable Polymeric Nanoparticles as the Delivery Carrier for Drug. Curr Drug Deliv 2016; 13: 494-499
- 12 Pandey A, Jain DS. Poly lactic-co-glycolic acid (PLGA) copolymer and its pharmaceutical application. In: V K Thakur and M K Thakur, Eds. Handbook of Polymers for Pharmaceutical Technologies. Hoboken, New Jerseyand , Salem, Massachusetts, USA: John Wiley & Sons, Inc. and Scrivener Publishing LLC; 2015: 151-172
- 13 Zhu Z, Min T, Zhang X, Wen Y. Microencapsulation of Thymol in Poly(lactide-co-glycolide) (PLGA): Physical and Antibacterial Properties. Mater 2019; 12: 1133
- 14 Yag G, Calis S, Arica-Yegin B. The effect of inorganic salt type and concentration on hydrophilic drug loading into microspheres using the emulsion/solvent diffusion method. Drug Dev Ind Pharm 2014; 40: 390-397
- 15 Jiang G, Thanoo BC, DeLuca PP. Effect of osmotic pressure in the solvent extraction phase on BSA release profile from PLGA microspheres. Pharm Dev Technol 2002; 7: 391-399
- 16 Padhi S, Mirza MA, Verma D, Khuroo T, Panda AK, Talegaonkar S, Khar RK, Iqbal Z. Revisiting the nanoformulation design approach for effective delivery of topotecan in its stable form: An appraisal of its in vitro behavior and tumor amelioration potential. Drug Deliv 2016; 23: 2827-2837
- 17 Bhatt Y, Shah D. Influence of additives on fabrication and release from protein loaded microparticles. Iran J Pharm Sci 2012; 8: 171-179
- 18 Taciak B, Białasek M, Braniewska A, Sas Z, Sawicka P. Kiraga Ł, Rygiel T, Król M. Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages. PLoS One 2018; 13: e0198943
- 19 Xiong S, Zhao X, Heng BC, Ng KW, Loo JS. Cellular uptake of Poly-(D,L-lactide-co-glycolide) (PLGA) nanoparticles synthesized through solvent emulsion evaporation and nanoprecipitation method. Biotechnol J 2011; 6: 501-508
- 20 de Castro CE, Ribeiro CAS, Alavarse AC, Albuquerque LJC, da Silva MCC, Jäger E, Surman F, Schmidt V, Giacomelli C, Giacomelli FC. Nanoparticle-Cell Interactions: Surface Chemistry Effects on the Cellular Uptake of Biocompatible Block Copolymer Assemblies. Langmuir 2018; 34: 2180-2188
- 21 Boscá L, Hortelano S. Mechanisms of nitric oxide-dependent apoptosis: Involvement of mitochondrial mediators. Cell Signal 1999; 11: 239-244
- 22 Martin KR, Ohayon D, Witko-Sarsat V. Promoting apoptosis of neutrophils and phagocytosis by macrophages: novel strategies in the resolution of inflammation. Swiss Med Wkly 2015; 145: w14056
- 23 Manayi A, Nabavi SM, Setzer WN, Jafari S. Piperine as a Potential Anti-cancer Agent: A Review on Preclinical Studies. Curr Med Chem 2018; 25: 4918-4928
- 24 Jamali T, Kavoosi G, Safavi M, Ardestani SK. In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell cultures and the study of their interaction mode with DNA. Sci Rep 2018; 8: 15787
- 25 Su H, Lei CT, Zhang C. Interleukin-6 Signaling Pathway and Its Role in Kidney Disease: An Update. Front Immunol 2017; 8: 405
- 26 Lee M, Rey K, Besler K, Wang C, Choy J. Immunobiology of Nitric Oxide and Regulation of Inducible Nitric Oxide Synthase. Results Probl Cell Differ 2017; 62: 181-207
- 27 Leutcha BP, Sema DK, Dzoyem JP, Ayimele GA, Nyongbela KD, Delie F, Alléman É, Sewald N, Meli Lannang A. Cytotoxicity of a new tirucallane derivative isolated from Stereospermum acuminatissimum K. Schum stem bark. Nat Prod Res 2020: 1–6
- 28 Dzoyem JP, Donfack ARN, Tane P, McGaw LJ, Eloff JN. Inhibition of nitric oxide production in LPS-stimulated RAW264.7 macrophages and 15-LOX activity by anthraquinones from Pentas schimperi . Planta Med 2016; 82: 1246-1251