Encapsulation of linalool in solid lipid nanoparticles Irina Pereira1,2,4, *Aleksandra Zielińska1,3, Francisco J. Veiga1,4, Amélia M. Silva2,5, Ana C. Santos1,6, Izabela Nowak3, Eliana B. Souto1,4 1
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, PORTUGAL, 2 Department of Biology and Environment, University of Trás-os-Montes and Alto Douro, PORTUGAL, 3 Faculty of Chemistry, Adam Mickiewicz University in Poznań, Poznań, POLAND, 4 REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, PORTUGAL, 5 Centre for Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro, PORTUGAL 6 Institute for Innovation and Health Research, Institute for Molecular and Cell Biology, Porto, PORTUGAL Corresponding e-mail:
[email protected]
Introduction Linalool (3,7-dimethyl-1,6-octadien-3-ol) [1] is an acyclic monoterpene tertiary alcohol. Linalool is a volatile, optically active compound present in the flower scent of different plant families, but more prevalent in Lamiaceae family. The chemical structure of linalool (Fig. 1) presents alcohol functional group, which makes the compound not only more polar and, therefore, it is soluble in water, but also more chemically reactive. On account of the hydroxyl group in the third carbon (C3) linalool exhibit chiral properties [2,3]. The two linalool enantiomers: (3S)-(+)-linalool (coriandrol) and (3R)-(-)-linalool (licareol) (Fig. 2) are chemically, biosynthetically, electrophysiologically, behaviorally distinct [3].
FIGURE 1. Structural formula of linalool.
FIGURE 2. Structural formula of coriandrol (left) and licareol (right).
According to recent reports, linalool has a wide range of biological effects which makes it suitable to be encapsulated in drug delivery nanocarriers [4,5] . Furthermore, it becomes a challenge to encapsulate linalool in lipid nanocarriers due to its hydrophilic structure. The aim of this study was to optimize the encapsulation of linalool in solid lipid nanoparticles (SLN).
Materials and Methods
Results
SLN formulations were produced by hot homogenization using high pressure homogenization (HPH). Thereupon production of linalool-loaded SLN a qualitative analysis was performed using dynamic light scattering (DLS). TABLE 1. Qualitative analysis of the obtained SLN-linalool formulations immediately (0 hours) and 24 hours (1 day) after production.
Formulations
SLN-linalool no. 1
SLN-linalool no. 2
SLN-linalool no. 3
Mean PDI ± SD
Mean ZP (mV) ±
0h
Size (nm) ± SD 113.7 ± 0.3
0.210 ± 0.007
SD 0.150 ± 0.196
24 h
148.9 ± 1.3
0.181 ± 0.020
- 4.030 ± 0.711
0h
149.3 ± 0.8
0.138 ± 0.013
-7.150 ± 0.592
24 h
314.4 ± 8.4
0.502 ± 0.028
0.050 ± 0.012
0h
95.5 ± 0.6
0.218 ± 0.002
0.122 ± 0.161
24 h
134.7 ± 1.4
0.189 ± 0.018
0.140 ± 0.127
Measurement time
Mean particle
Firstly, an optimization process to find the correct proportions of each ingredient has been carried out, as well as the production parameters that resulted in formulations with a small particle size and polydispersity index (PDI) below 0.5. Two formulations, SLNlinalool no. 1 (with 1 %wt. linalool; 4 %wt. solid lipid and 1.25 %wt. surfactant) and no. 3 (with 1 %wt. linalool; 4 %wt. solid lipid and 2.5 %wt. surfactant) showed satisfactory results (Table 1). Subsequently, linalool-loaded SLN dispersions were storage at different temperatures: 4, 25 and 40οC for a period of 1 month (Table 2). TABLE 2. Qualitative analysis of SLN-linalool 1 and 3 after 1 month in different storage temperatures.
Formulations Measurement time
SLN-linalool no. 1
Mean particle Size (nm) ± SD
Mean PDI ± SD
Mean ZP (mV) ± SD
4
1268.0 ± 327.0
0.594 ± 0.352
-0.047 ± 0.043
25
314.6 ± 65.2
0.512 ± 0.081
0.034 ± 0.050
40
149.0 ± 1.9
0.170 ± 0.013
0.112 ± 0.302
4
3797.3 ± 555.7
0.302 ± 0.058
-0.047 ± 0.113
25
127.3 ± 0.5
0.117 ± 0.013
-0.116 ± 0.204
40
84.2 ± 0.9
0.210 ± 0.012
0.102 ± 0.214
1 month
*h – Hours; SD - Standard deviation
SLN-linalool no. 3
Storage Temperature (οC)
1 month
*h – Hours; SD - Standard deviation
Conclusions The best storage temperature to obtain smaller and stable linalool-loaded SLN dispersions was at 40 ºC. In summary, linalool-loaded SLN no. 3 was the most stable formulation resulting from the optimization process since it showed the smallest mean particle size and PDI values, both at 25 and 40 ºC. AKNOWLEDGMENTS: The authors would like to acknowledge the financial support received through the projects MERANET/0004/2015 and UID/QUI/50006/2013, from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. The authors also acknowledge FCT for the scholarship SFRH/BD/109261/2015. References: [1] Asbahani, A. E.; Miladi, K.; Badri, W.; Sala, M.; Addi, E. H. A.; Casabianca, H.; Mousadik, A. E.; Hartmann, D.; Jilale, A.; Renaud, F. N. R.; Elaissari, A. Essential oils: from extraction to encapsulation. International journal of pharmaceutics, 2015, 483, 220-243 [2] Aprotosoaie, A. C.; Hăncianu, M.; Costache, I. I.; Miron, A. Linalool: a review on a key odorant molecule with valuable biological properties. Flavour and fragrance journal, 2014, 29, 193-219 [3] Raguso, R. A. More lessons from linalool: insights gained from a ubiquitous floral volatile. Current Opinion in Plant Biology, 2016, 32, 31-36 [4] Han, H. D.; Cho, Y. J.; Cho, S. K.; Byeon, Y.; Jeon, H. N.; Kim, H. S.; Kim, B. G.; Bae, D. S.; Lopez-Berestein, G.; Sood, A. K.; Shin, B. C.; Park, Y. M.; Lee, J. W. Linalool-incorporated nanoparticles as a novel anticancer agent for epithelial ovarian carcinoma. Molecular Cancer Therapeutics, 2016, 15, 618-627 [5] Shi, F.; Zhao, Y.; Firempong, C. K.; Xu, X. Preparation, characterization and pharmacokinetic studies of linalool-loaded nanostructured lipid carriers. Pharmaceutical biology, 2016, 54, 2320-2328
