OPTIMIZATION OF LUTEOLIN-LOADED TRANSFERSOME USING RESPONSE SURFACE METHODOLOGY
Objective: This research was carried out to optimize luteolin-loaded transfersome formula with independent variables such as lipidâ€“surfactant (total
lipid) concentration and luteolin concentration.
Methods: Luteolin-loaded transfersome was optimized by response surface methodology based on four parameters, namely, particle size (Z-average),
polydispersity index, zeta potential, and entrapment efficiency. The transfersome formula was prepared using central composite design, and the
selected independent variables were the total lipid (mixture of phospholipid and Tween 80) and luteolin concentrations. 14 formulas of luteolinloaded
transfersome were prepared by thin film hydration, followed by the sonication method.
Results: The total lipid and luteolin concentration significantly affected the entrapment efficiency only. The other parameters were not affected by a
change in these variables. The optimum formula of 4.88% total lipid and 0.5% luteolin with desirability value of 0.609 conformed with the prediction
parameters. Vesicle imaging using transmission electron microscopy revealed spherical particles and the occurrence of particle aggregation. The
optimum formula of luteolin-loaded transfersome possessed the following characteristics: Particle size of 286.03Â±8.46 nm, polydispersity index
of 0.480Â±0.013, zeta potential of -18.67Â±0.379 mV, and entrapment efficiency of 94.97Â±0.28 %. However, these values did not correspond to the
predicted values and were confirmed by the low adjusted and predicted R-squared values.
Conclusion: This method can be applied to optimize the entrapment efficiency, and in the future, it can be used for further optimizing formula of
transfersome by including more variables.
luteolin. Mini Rev Med Chem 2009;9(1):31-59.
2. Van Hoorn DE, Nijveldt RJ, Van Leeuwen PA, Hofman Z, Mâ€™Rabet L,
De Bont DB, et al. Accurate prediction of xanthine oxidase inhibition
based on the structure of flavonoids. Eur J Pharmacol 2002;451(2):111-8.
3. Abelson JN, Simon MI, Colowick SP, Kaplan NO. In: Eichman BF,
editor. Methods in Enzymology. New York: Shirley Light of Academic
4. Abidin L, Mujeeb M, Imam SS, Aqil M, Khurana D. Enhanced
transdermal delivery of luteolin via non-ionic surfactant-based
vesicle: Quality evaluation and anti-arthritic assessment. Drug Deliv
5. Benson HA. Transdermal drug delivery: Penetration enhancement
techniques. Curr Drug Deliv 2005;2(1):23-33.
6. El Zaafarany GM, Awad GA, Holayel SM, Mortada ND. Role of edge
activators and surface charge in developing ultradeformable vesicles
with enhanced skin delivery. Int J Pharm 2010;397(1-2):164-72.
7. Raissi S. Developing new processes and optimizing performance
using response surface methodology. World Acad Sci Eng Technol
8. BaÅŸ D, BoyacÄ± Ä°H. Modeling and optimization I: Usability of response
surface methodology. J Food Eng 2007;78(3):836-45.
9. Krishnaiah D, Bono A, Sarbatly R, Nithyanandam R, Anisuzzaman SM.
Optimisation of spray drying operating conditions of Morinda
citrifolia L. Fruit extract using response surface methodology. J King
Fig. 1: Plot contour showed the interaction of total lipid and luteolin concentration on (a) particle size (Z-average d.nm),
(b) polydispersity index, (c) zeta potential, and (d) entrapment efficiency parameters
Fig. 2: Luteolin-loaded transfersome vesicle observed by
transmission electron microscopy imaging (a) Ã—10000 and (b)
Int J App Pharm, Special Issue (October)
Setyawati et al.
Saud Univ 2012;27(1):26-36.
10. Minitab. What is a Response Surface Design? 2016. Available from:
11. Shaji J, Bhatia V. Dissolution enhancement of atovaquone through
cyclodextrin complexation and phospholipid solid dispersion. Int J
Pharm Pharm Sci 2013;5(3):642-50.
12. Chen C. Zetasizer Nano Customer Training. Taipei: DKSH Taiwan
13. Honary S, Zahir F. Effect of zeta potential on the properties of
nano-drug delivery systems-a review (Part 2). Trop J Pharm Res
14. Lou Z, Chen S, Xia GL, Yan M, Zhang Z, Gao J. Comparative
pharmacokinetic study of luteolin after oral administration of Chinese
herb compound prescription JiMaiTong in Spontaneous Hypertensive
Rats (SHR) and Sprague Dawley (SD) rats. Afr J Pharm Pharmacol
15. Suhaim SH, Hisam RH, Rosli NA. Effects of formulation parameters
on particle size and polydispersity index of Orthosiphon stamineus
loaded nanostructured lipid carrier. Akademia Baru J Adv Appl Sci Eng
16. Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, et al. Pharmaceutical
particle technologies: An approach to improve drug solubility,
dissolution and bioavailability. Asian J Pharm Sci 2014;9(6):304-16.
17. Woodbury DJ, Richardson ES, Grigg AW, Welling RD, Knudson BH.
Reducing liposome size with ultrasound: Bimodal size distributions.
J Liposome Res 2006;16(1):57-80.
18. Shaji J, Lal M. Preparation, optimization and evaluaion of transferosomal
formulation for enhanced transdermal delivery of a cox-2 inhibitor. Int J
Pharm Pharm Sci 2014;6(1):467-77.
19. Yandrapati RK. Effect of Lipid Composition on the Physical Properties
of Liposomes: A Light Scattering Study, Thesis. Missouri: Missouri
University of Science and Technology; 2012.
20. Carneiro-Da-Cunha MG, Cerqueira MA, Souza BW, Teixeira JA,
Vicente AA. Influence of concentration, ionic strength and PH on zeta
potential and mean hydrodynamic diameter of edible polysaccharide
solutions envisaged for multinanolayered films production. Carbohydr
21. Colletier JP, Chaize B, Winterhalter M, Fournier D. Protein encapsulation
in liposomes: Efficiency depends on interactions between protein and
phospholipid bilayer. BMC Biotechnol 2002;2(9):9.
22. Mourabet M, El Rhilassi A, El Boujaady H, Bennani-Ziatni M,
Taitai A. Use of response surface methodology for optimization of
fluoride adsorption in an aqueous solution by brushite. Arab J Chem