Sains Malaysiana 51(7)(2022): 2119-2128


Optimization and Characterization of Fatty Acid Esters (FAES) Based Nanostructured Lipid Carrier (NLC) by Box-Behnken Analysis

(Pengoptimuman dan Pencirian Ester Asid Lemak (FAES) Berasaskan Pembawa Lipid Berstruktur Nano (NLC) oleh Analisis Box-Behnken)




Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Federal Territory, Malaysia


Diserahkan: 29 Ogos 2021/Diterima: 30 Disember 2021



An unfavorable rate of toxicity and hydrophobicity of active substance in water has prompted the development of an improved active ingredients delivery systems such as nanostructured lipid carriers (NLC). This present study investigates varying components of NLCs compositions to achieve an optimized and stable colloidal suspension of NLCs through Box-Behnken design analysis for potential use as an active substance carrier system. The optimised formulation is comprised of 2.9% stearic acid, 0.4% MCT, 0.3% IPM, 0.37% Tween 20, 0.23% Span 20 and 96% deionised water (DW). The mean particle size, polydispersity index, and zeta potential of the optimized NLCs were 322±13.5 nm, 0.199±0.04, and -36±0.1 mV, respectively. Based on the TEM micrograph, NLCs can be observed as having an elongated spherical shape with a dense appearance.


Keywords: Box-Behnken design; isopropyl myristate; medium-chain triglyceride; nanostructured lipid carrier; surfactant



Tahap ketoksikan dan sifat hidrofobik sesetengah bahan aktif yang kurang memberangsangkan telah mendorong kepada kajian berkenaan sistem penyampaian ubat yang lebih baik seperti pembawa lipid berstruktur nano (NLC). Justeru, penyelidikan ini mengkaji potensi NLC sebagai sistem pembawa ubat yang baik melalui penelitian kepelbagaian komponen komposisi NLC untuk mencapai suspensi koloid yang stabil dan optimum melalui analisis reka bentuk Box-Behnken. Formulasi yang dioptimumkan terdiri daripada 2.9% asid stearat, 0.4% MCT, 0.3% IPM, 0.37% Tween 20, 0.23% Span 20 dan 96% air deionisasi (DW). Saiz zarah min, indeks polidispersi dan potensi zeta NLC yang optimum masing-masing adalah 322±13.5 nm, 0.199±0.04 dan -36±0.1 mV. Berdasarkan mikrograf TEM, NLC dapat dilihat memiliki bentuk sfera memanjang dengan penampilan yang padat.


Kata kunci: Isopropil miristat; pembawa lipid berstruktur nano; reka bentuk Box-Behnken; surfaktan; trigliserida rantai sederhana (MCT)



Bnyan, R., Khan, I., Ehtezazi, T., Saleem, I., Gordon, S., O'Neill, F. & Roberts, M. 2018. Surfactant effects on lipid-based vesicles properties. Journal of Pharmaceutical Sciences 107(5): 1237-1246.

Dudhipala, N. & Gorre, T. 2020. Neuroprotective effect of ropinirole lipid nanoparticles enriched hydrogel for parkinson’s disease: In vitro, ex vivo, pharmacokinetic and pharmacodynamic evaluation. Pharmaceutics 12(5): 448.

Eh Suk, V.R., Latif, F.M., Teo, Y.Y. & Misran, M. 2020. Development of nanostructured lipid carrier (NLC) assisted with polysorbate nonionic surfactants as a carrier for L -ascorbic acid and Gold Tri.E 30. Journal of Food Science and Technology 57(9): 3259-3266.

Ferreira, S.C., Bruns, R.E., Ferreira, H.S., Matos, G.D., David, J.M., Brandão, G.C., da Silva, E.P., Portugal, L.A., Dos Reis, P.S., Souza, A.S. & Dos Santos, W.N.L. 2007. Box-Behnken design: An alternative for the optimization of analytical methods. Analytica Chimica Acta 597(2): 179-186.

Gardouh, A.R., Faheim, S.H., Noah, A.T. & Ghorab, M.M. 2018. Influence of formulation factors on the size of nanostructured lipid carriers and nanoemulsions prepared by high shear homogenization. International Journal of Pharmacy and Pharmaceutical Sciences 10(4): 61-75.

Gordillo-Galeano, A. & Mora-Huertas, C.E. 2018. Solid lipid nano-particles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. Eur. J. Pharm. Biopharm. 133: 285-308.

Han, F., Li, S., Yin, R., Liu, H. & Xu, L. 2008. Effect of surfactants on the formation and characterization of a new type of colloidal drug delivery system: Nanostructured lipid carriers. Colloids and Surfaces A: Physicochemical and Engineering Aspects 315(1-3): 210-216.

Kaur, P., Garg, T., Rath, G., Murthy, R.S.R. & Goyal, A.K. 2016. Development, optimization and evaluation of surfactant-based pulmonary nanolipid carrier system of paclitaxel for the management of drug resistance lung cancer using Box-Behnken. Drug Delivery 23(6): 1912-1925.

Khezri, K., Saeedi, M. & Dizaj, S.M. 2018. Application of nanoparticles in percutaneous delivery of active ingredients in cosmetic preparations. Biomedicine & Pharmacotherapy 106: 1499-1505.

Kothekar, S.C., Ware, A.M., Waghmare, J.T. & Momin, S.A. 2007. Comparative analysis of the properties of Tween‐20, Tween‐60, Tween‐80, Arlacel‐60, and Arlacel‐80. Journal of Dispersion Science and Technology 28(3): 477-484.

Mishra, D.K., Shandilya, R. & Mishra, P.K. 2018. Lipid based nanocarriers: A translational perspective. Nanomedicine: Nanotechnology, Biology and Medicine 14(7): 2023-2050.

Müller, R.H., Radtke, M. & Wissing, S.A. 2002. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Advanced Drug Delivery Reviews 54: S131-S155.

Ni, S., Sun, R., Zhao, G. & Xia, Q. 2014. Quercetin loaded nanostructured lipid carrier for food fortification: Preparation, characterization and in vitro study. Journal of Food Process Engineering 38(1): 93-106.

Sakamula, R., Yata, T. & Wachiryah, T-A. 2021. Effects of alpha-mangostin encapsulated in nanostructured lipid carriers in mice with cerebral ischemia reperfusion injury. Sains Malaysiana 50(7): 2007-2015.

Sarheed, O., Dibi, M. & Ramesh, K.V.R.N.S. 2020. Studies on the effect of oil and surfactant on the formation of alginate-based O/W lidocaine nanocarriers using nanoemulsion template. Pharmaceutics 12(12): 1223.

Severino, P., Pinho, S.C., Souto, E.B. & Santana, M.H.A. 2011. Polymorphism, crystallinity and hydrophilic-lipophilic balance of stearic acid and stearic acid-capric/caprylic triglyceride matrices for production of stable nanoparticles. Colloids and Surfaces B: Biointerfaces 86(1): 125-130.

Shirodkar, R.K., Kumar, L., Mutalik, S. & Lewis, S. 2019. Solid lipid nanoparticles and nanostructured lipid carriers: Emerging lipid based drug delivery systems. Pharmaceutical Chemistry Journal 53(5): 440-453.

Souto, E.B. & Müller, R.H. 2006. Investigation of the factors influencing the incorporation of clotrimazole in SLN and NLC prepared by hot high-pressure homogenization. Journal of Microencapsulation 23(4): 377-388.

Subramaniam, B., Siddik, Z.H. & Nagoor, N.H. 2020. Optimization of nanostructured lipid carriers: Understanding the types, designs, and parameters in the process of formulations. Journal of Nanoparticle Research 22(6): 1-29.

Teo, Y.Y., Misran, M., Low, K.H. & Zain, S.M. 2011. Effect of unsaturation on the stability of C18 polyunsaturated fatty acids vesicles suspension in aqueous solution. Bulletin of the Korean Chemical Society 32(1): 59-64.

Vieira, R., Severino, P., Nalone, L.A., Souto, S.B., Silva, A.M., Lucarini, M., Durazzo, A., Santini, A. & Souto, E.B. 2020. Sucupira oil-loaded nanostructured lipid carriers (NLC): Lipid screening, factorial design, release profile, and cytotoxicity. Molecules 25(3): 685.

Yew, H.C. & Misran, M. 2019. Progress in drug discovery & biomedical science characterization of fatty acid based nanostructured lipid carrier (NLC) and their sustained release properties. Progress in Drug Discovery & Biomedical Science 2(1):