Development of Nanoparticles Pegagan Leaves Ethanolic Extract (centella asiatica (L.) Urban) using Variation Concentration of Poly-Lactic-CO-Glycolic Acid (PLGA) Polymer

Elsa Fitria Apriani(1), Mardiyanto Mardiyanto(2*), Rika Destiana(3)

(1) Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Sriwijaya University, South Sumatra, Indonesia
(2) Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Sriwijaya University, South Sumatra, Indonesia
(3) Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Sriwijaya University, South Sumatra, Indonesia
(*) Corresponding Author


Pegagan is a plant that plays an important role in health because of its secondary metabolite. However, many secondary metabolites tend to be unstable when exposed to UV light and oxygen such as flavonoid and terpenoid. The purpose of this study was to formulate the ethanolic extract of pegagan leaves into nanoparticle preparations to increase the stability of the extract. Nanoparticle preparations were made using the emulsion solvent evaporation method using Poly-Lactic-Co-Glycolic Acid (PLGA) and polyvinyl alcohol (PVA). PLGA acts as a polymer that will coat the extract and PVA as a stabilizer. Variations in the concentration of PLGA used were 50 mg, 75 mg, and 100 mg, while the concentration of PVA used was 40 mg and the extract concentration was 158 mg. Determination of the best formula is done by looking at the results of the percent encapsulation efficiency obtained from the three formulas, namely 93.68%, 85.35%, and 88.76%, respectively. Based on these results, formula 1 was determined as the best formula. The particle size obtained in the best formula was 288.1667±3.4195 nm, the polydispersity index (PDI) was 0.371±0.0045 and the zeta potential value was -10.6333±0.1154. A physical stability test (cycling test method) of the best formula found a decrease in pH of 0.54 and no organoleptic changes or precipitate formed.


Pegagan leaves ethanolic extract; PLGA; PVA; Nanoparticles

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Al-Ishaq, R.K., Abotaleb, M., Kubatka, P., Kajo, K. & Büsselberg, D., 2019, Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels, Biomolecules. 9 (9), 430. Doi:10.3390/biom9090430

Apriani, E.F., Nurleni, N., Nugrahani, H.N. & Iskandarsyah, I., 2018, “STABILITY TESTING OF AZELAIC ACID CREAM BASED ETHOSOME”, Asian Journal of Pharmaceutical and Clinical Research. 11 (5), 270-273. doi:10.22159/ajpcr.2018.v11i5.23218.

Apriani, E.F., Rosana, Y. & Iskandarsyah, I., 2019, Formulation, characterization, and in vitro testing of azelaic acid ethosome-based cream against Propionibacterium acnes for the treatment of acne, J Adv Pharm Technol Res. 10 (2), 75-80. doi: 10.4103/japtr.JAPTR_289_18

Apriani, E.F., Ahmadi, A. & Noviani, V., 2021, Formulation and Evaluation of Water Fraction Hair Tonic Containing Flavonoids from Ethanolic Extract of Green Tea Leaves (Camellia sinensis L.), Tradicional Medicine Journal. 26 (2), 77-83. doi: 10.22146/mot.53665

Azmin, S.N.H.M. & Nor, M.S.M., 2020, Chemical fingerprint of Centella Asiatica’s bioactive compounds in the ethanolic and aqueous extracts, Advances in Biomarker Sciences and Technology. 2, 35-44. doi: 10.1016/j.abst.2020.10.001

Buzea, C., Pacheco, II. & Robbie, K., 2007, Nanomaterials and nanoparticles: sources and toxicity, Biointerphases. 2 (4), MR17-71. doi: 10.1116/1.2815690.

Bylka, W., Znajdek-Awizen, P., Studzinska-Sroka, E., Danczak-Pazdrowska, A. & Brzenzinska, M., 2014, Centella asiatica in Dermatology: An Overview, Phytotherapy Research. 28 (8), 1117-1124. doi: 10.1002/ptr.5110

Chandrika, U.G. & Kumara, P.A., 2015, Gotu Kola (Centella asiatica): Nutritional properties and plausible health benefits, Adv Food Nutr Res. 76, 125-157. doi:10.1016/bs.afnr.2015.08.001

Clogston, J.D. & Patri, A.K., 2011, Zeta potential measurement. Methods in molecular biology. 697, 63–70. Doi:10.1007/978-1-60327-198-1_6

Danaei, M., Dehghankhold, S., Ataei, F., Hasanzadeh, D., Javanmard, R., Dokhani, A., Khorasani, S. & Mozafari, M.R., 2018, Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems, Pharmaceutics. 10 (2), 1-17. Doi: 10.3390/pharmaceutics10020057

Gray, N.E., Magana, A.A., Lak, P., Wright, K.M., Quinn, J., Stevens, J.F., Maier, C.S. & Soumyanath A., 2018, Centella asiatica – Phytochemistry and mechanisms of neuroprotection and cognitive enhancement, Phytochem Rev. 17 (1), 161–194. doi: 10.1007/s11101-017-9528-y

Harborne, J.B., 1984, Methods of phytochemistry: A Guide to Modern Techniques of Plant Analysis, Springer, United Kingdom. doi: 10.1007/978-94-009-5570-7

Hoshyar, N., Gray, S., Han, H. & Bao, G., 2016, The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction, Nanomedicine. 11 (6), 673–692. Doi:10.2217/nnm.16.5

Indarti, K., Apriani, E.F., Wibowo, A.E. & Simanjuntak, P., 2019, Antiontioxidant Activity of Ethanolic Extract and Various Fractions from Green Tea (Camellia sinensis L.) Leaves, Pharmacognosy Journal. 11 (4), 771-776. doi: 10.5530/pj.2019.11.122

Ioannou, I., Chekir, L. & Ghoul, M., 2020, Effect of Heat Treatment and Light Exposure on the Antioxidant Activity of Flavonoids, Processes. 8 (1078), 1-17. doi:10.3390/pr8091078

Irham, W.H., Tamrin, Marpaung, L. & Marpongahtun., 2019, Bioactive Compounds In Pegagan Leaf (Centella asiatica L. Urban) for Wound Healing, Journal of Physics: Conference Series. 1232, 1-5. doi:10.1088/1742-6596/1232/1/012019

Ismail, R., Sovany, T., Gacsi, A., Ambrus, R., Katona, G., Imre, N. & Csoka, I., 2019, Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery, Pharm Res. 36 (99): 1-16. Doi: 10.1007/s11095-019-2620-9

Jalalian, M., Mirkazemi, S.M. & Alamolhoda, S., 2016, The effect of poly vinyl alcohol (PVA) surfactant on phase formation and magnetic properties of hydrothermally synthesized CoFe2O4 nanoparticles, Journal of Magnetism and Magnetic Materials. 419, 363-367. Doi:10.1016/j.jmmm.2016.06.045.

Kemala, T., Budianto, E. & Suegiyono, B., 2012, Preparation and Characterization of Microspheres Based on Blend of Poly(Lactic Acid) and Poly (ε-Caprolactone) with Poly(Vinyl Alcohol) as Emulsifier, Arabian Journal of Chemistry. 5 (1), 103-108. doi: 10.1016/j.arabjc.2010.08.003

Khan, M.T.H. & Orhan, I.E., 2012, Centella asiatica (L.) Urban: From Traditional Medicine to Modern Medicine with Neuroprotective Potential, Evidence-Based Complementary and Alternative Medicine. 2012, 1-8. doi:10.1155/2012/946259

Kopustinskiene, D.M., Jakstas, V., Savickas, A. & Bernatoniene, J., 2020, Flavonoids as Anticancer Agents, Nutrients. 12 (2), 457. Doi:10.3390/nu12020457

Maaliki, D., Shaito, A.A., Pintus, G., El-Yazbi, A. & Eid, A.H., 2019, Flavonoids in hypertension: a brief review of the underlying mechanisms, Curr Opin Pharmacol. 45, 57-65. doi: 10.1016/j.coph.2019.04.014. Epub 2019 May 16. PMID: 31102958.

Maleki, S.J., Crespo, J.F. & Cabanillas, B., 2019, Anti-inflammatory effects of flavonoids, Food Chem. 299, 125124. doi: 10.1016/j.foodchem.2019.125124.

Mardiyanto, M., Fithri, N.A. & Raefty, W., 2018, Optimasi Formula Submikro Partikel Poly (Lactic-co-Glycolic Acid) Pembawa Betametason Valerat dengan Variasi Konsentrasi Poly (Vinyl Alcohol) dan Waktu Sonikasi, Jurnal Sains Farmasi & Klinis (J Sains Farm Klin). 5 (1), 55-65. doi: 10.25077/jsfk.5.1.55-65.2018

Mitchell, J.M., Billingsley, M.M., Haley, R.M., Wechsler, M.E., Peppas, N.A. & Langer, R., 2021, Engineering precision nanoparticles for drug delivery, Nature Reviews. 20, 101-124. Doi: 10.1038/s41573-020-0090-8

Nasution, M.Y., Restuati, M., Pulungan, A.S.S., Pratiwi, N. & Diningrat, D.S., 2018, Antimicrobial Activities of Centella asiatica Leaf and Root Extracts on Selected Pathogenic Micro-organisms, Journal of Medical Sciences. 18, 198-204. doi: 10.3923/jms.2018.198.204

Pakulska, M.M., Donaghue, I.E., Obermeyer, J.M., Tuladhar, A., McLaughlin, C.M., Shendruk, T.N. & Shoichet, M.S., 2016, Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles, Sciences Advances. 2 (5): 1-10. Doi: 10.1126/sciadv.1600519

Park, J.H., Choi, J.Y., Son, D.J., Park, E.K., Song, M.J., Hellström, M. & Hong, J.T., 2017, Anti-inflammatory effect of titrated extract of Centella asiatica in phthalic anhydride-induced allergic dermatitis animal model, Intl J Mol Sci. 18, 738. doi: 10.3390/ijms18040738

Pool, H., Quintanar, D., Figueroa, J., Mano, C., Bechara, E., Godinez, L. & Mendoza, S., 2012, Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles, Journal of Nanomaterials. 2012, 1-12. Doi:10.1155/2012/145380

Prasetyo, Y.A., Husni, P. & Mita, S.R., 2017, Long-Circulating Nanopartikel
Menggunakan Polimer PLGA (Poly-Lactic-co-Glicolyc Acid) dan
Poloxamer, Farmaka. 15 (1), 237-247. doi: 10.24198/jf.v15i1.13322

Puttarak, P. & Brantner, A., 2016, Biological Activities and Stability of a Standardized Pentacyclic Triterpene Enriched Centella asiatica Extract. Natural Product Sciences. 22 (1), 20. doi: 10.20307/nps.2016.22.1.20

Rahayu, N.K.T., Permana, I.D.G.M. & Puspawati, G.A.K.D., 2020, Pengaruh
Waktu Maserasi terhadap Aktivitas Antioksidan Ekstrak Daun Pegagan,
Jurnal Itepa. 9 (4), 482-489. doi: 10.24843/itepa.2020.v09.i04.p12

Ramesova, S., Sokolova, R., Degano, I., Bulickova, J., Zabka, J. & Gal, M., 2011, On the stability of the bioactive flavonoids quercetin and luteolin under oxygen-free conditions, Analytical and bioanalytical chemistry. 402 (2), 975-982. doi: 10.1007/s00216-011-5504-3

Rana, A.C. & Gulliya B., 2019, Chemistry and Pharmacology of Flavonoids- A Review, Indian Journal of Pharmaceutical Education and Research. 53 (1), 8-20. Doi: 10.5530/ijper.53.1.3

Rasmussen, M.K., Pedersen, J.N. & Marie, R., 2020, Size and surface charge characterization of nanoparticles with a salt gradient, Nat Commun. 11 (2337), 1-8. Doi: 10.1038/s41467-020-15889-3

Samimi, S., Maghsoudnia, N., Eftekhari, R.B. & Dorkoosh, F., 2019, Chapter 3 - Lipid-Based Nanoparticles for Drug Delivery Systems, In Micro and Nano Technologies, Characterization and Biology of Nanomaterials for Drug Delivery, Elsevier, 47-76. Doi:10.1016/B978-0-12-814031-4.00003-9.

Sharma, K., Ko, E.Y., Assefa, A.D., Ha, S., Nile, S.H., Lee, E.T. & Park, S.W., 2015, Temperature-dependent studies on the total phenolics, flavonoids, antioxidant activities, and sugar content in six onion varieties, Journal of Food and Drug Analysis. 23 (2), 243-252. Doi:/10.1016/j.jfda.2014.10.005.

World Health Organization, 1998, Quality control methods for medicinal plant materials, Geneva.

Xie, Y., Yang, W., Tang, F., Chen, X. & Ren, L., 2015, Antibacterial activities of flavonoids: structure-activity relationship and mechanism, Curr Med Chem. 22 (1), 132-149. doi: 10.2174/0929867321666140916113443.


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