THE EVALUATION OF ACTIVITY AND STABILITY OF ISOLATED BROMELAIN FROM PINEAPPLE CORES (ANANAS COMOSUS [L.] MERR) AND IN VITRO PENETRATION TEST OF NANOEMULSION TOPICAL BASE
Keywords:Pineapple core, Bromelain, Nanoemulsion, Enzyme activity, Franz diffusion cell
Objective: Oral administration of bromelain as an anti-inflammation therapy still faces several challenges, such as the risk of contact with the gastric fluid and its low absorption rate. Therefore, bromelain isolated from the pineapple core will be formulated as a topical base in a nanoemulsion to increase its stability, activity, and ability to penetrate the skin.
Methods: Bromelain was isolated from pineapple core using ammonium sulfate precipitation and dialysis, and then the isolated fraction was loaded into topical nanoemulsion for subsequent evaluation of its characteristics, stability, enzymatic activity, and for in vitro study of penetration using Franz diffusion cell.
Results: The highest specific activity of bromelain fractions found in ammonium sulfate concentration is around 20–50%. After being dialyzed, the bromelain fraction showed an increase in specific activity 2.78-fold as compared to crude extract. The characteristics of bromelain nanoemulsion showed a globule size of 21.37±1.8 nm with a polydispersity index (pdI) 0.323±0.049, oil in water (o/w) type, and the type of rheology was plastic flow. The nanoemulsion stability base was observed, and there was no phase separation after centrifugation. Bromelain in nanoemulsion base showed a proteolytic activity of 5.00 U/ml with a protein content of 154.28 mg/l. In vitro penetration studies using Franz diffusion cell for 8 h showed isolated bromelain in nanoemulsion base has a total cumulative number value of 1386.94 μg/cm2 with penetrated velocity/flux (J) of 45.93 μg/cm2 h.
Conclusion: The results showed promise for bromelain loaded into nanoemulsion as a vehicle for topically administered therapeutic enzymes.
Pertiwi I, Setiasih S, Handayani S, Hudiyono S. Bromelain nanoemulsion formulation resulting from partial purification of pineapple core (Ananas comosus [L.] merr) and in vitro testing as antiinflammation. AIP Conf Proc 2020;2243:030017.
Novaes LC deL, Jozala AF, Lopes AM, Santos-Ebinuma Vde C, Mazzola PG, Junior AP. Stability, purification, and applications of bromelain: a review. Biotechnol Prog 2016;32:5-13.
Pavan R, Jain S, Shraddha, Kumar A. Properties and therapeutic application of bromelain: a review. Biotechnol Res Int 2012;2012:976203.
Wu SY, Hu W, Zhang B, Liu S, Wang JM, Wang AM. Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds. J Surg Res 2012;176:503-9.
Muller S, Marz R, Schmolz M, Drewelow B, Eschmann K, Meiser P. Placebo-controlled randomized clinical trial on the immunomodulating activities of low-and high-dose bromelain after oral administration–new evidence on the antiinflammatory mode of action of bromelain. Phyther Res 2013;27:199-204.
Ataide JA, Gerios EF, Mazzola PG, Souto EB. Bromelain-loaded nanoparticles: a comprehensive review of the state of the art. Adv Colloid Interface Sci 2018;254:48-55.
Suciati T, Aliyandi A. Development of transdermal nanoemulsion formulation for simultaneous delivery of protein vaccine and artin-m adjuvant. Int J Pharm Pharm Sci 2014;6:536-46.
Gupta PK, Pandit JK, Kumar A, Swaroop P, Gupta S. Pharmaceutical nanotechnology novel nanoemulsion–high energy emulsification preparation, evaluation and application. Pharma Res 2010;3:117-38.
Rachmawati H, Sulastri E, Iwo MI, Safitri D, Rahma A. Bromelain encapsulated in self-assembly nanoemulsion exhibit better debriment effect in an animal model of burned skin. J Nano Res 2016;40:158-66.
Setiasih S, Prabowo HA, Budianto E, Hudiyono S. Dissolution profiles of partially purified bromelain from pineapple cores [Ananas comosus (L.) Merr] encapsulated in glutaraldehyde-crosslinked chitosan. J Appl Pharm Sci 2018;8:17–24.
Musfiroh FF, Setiasih S, Handayani S, Hudiyono S, Ilyas NM. In vivo antiplatelet activity aggregation assay of bromelain fractionate by ethanol from extract pineapple core (Ananas comosus [L.] Merr). IOP Conf Ser: Mat Sci Eng 2018;299:012017.
Scopes RK. Separation by precipitation. In: Cantor CR, Manor P, Ormston K. editors. Protein Precipitation. New York: Springer; 1982. p. 39-66.
Chuacharoen T, Prasongsuk S, Sabliov CM. Effect of surfactant concentrations on physicochemical properties and functionality of curcumin nanoemulsions under conditions relevant to commercial utilization. Molecules 2019;24:2744.
Tsai MJ, Fu YS, Lin YH, Huang YB, Wu PC. The effect of nanoemulsion as a carrier of a hydrophilic compound for transdermal delivery. PloS One 2014;9:e102850.
Basera K, Bhatt G, Kothiyal P, Gupta P. Nanoemulgel: a novel formulation approach for topical delivery of hydrophobic drugs. World J Pharm Pharm Sci 2015;4:1871-6.
El-Hadi AA, Ahmed HM, Zaki RA, Mohsen AM. Enhanced enzymatic activity of Streptomyces griseoplanus L-asparaginase via its incorporation in an oil-based nanocarrier. Int J Appl Pharm 2020;12:203-10.
Ferreira CD, Nunes IL. Oil nanoencapsulation: development, application, and incorporation into the food market. Nanoscale Res Lett 2019;14:1-13.
Garg A, Aggarwal D, Garg S, Singla AK. Spreading of semisolid formulations an update. Pharm Technol 2002;26:84-105.
Kishore RSK, Kiese S, Fischer S, Pappenberger A, Grauschopf U, Mahler HC. The degradation of polysorbates 20 and 80 and its potential impact on the stability of biotherapeutics. Pharm Res 2011;28:1194-210.
Novaes LCdeL, Jozala AF, Mazzola PG, Junior AP. The influence of pH, polyethylene glycol and polyacrylic acid on the stability of stem bromelain. Brazilian J Pharm Sci 2014;50:371-80.
Bresolin IRAP, Bresolin ITL, Mazzola PG, Tambourgi EB. Incorporation of bromelain into dermatological bases: accelerated stability studies. J Chem Eng 2014;8:270-7.
Rachmawati H, Budiputra DK, Mauludin R. Curcumin nanoemulsion for transdermal application: formulation and evaluation. Drug Dev Ind Pharm 2015;41:560-6.
How to Cite
Copyright (c) 2021 Hegi Adi Prabowo, Ainur Rohmah, Siswati Setiasih, Sumi Hudiyono, Sri Handayani
This work is licensed under a Creative Commons Attribution 4.0 International License.