Nanostructured lipid carriers (NLCs) composed of argan oil, the potential novel vehicle for caffeine delivery to stratum corneum and hair follicles

Document Type : Research Paper


1 Department of Pharmaceutics, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

2 School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran

3 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran


Objective(s): The optimal formulation of Nanostructured lipid carriers (NLCs) that contains argan oil and caffeine was considered to be developed as a topical treatment for hair loss. 
Materials and Methods: 26 batches were prepared according to the central composite design. Dynamic light scattering technique showed size, polydispersity index (PDI), and zeta potential, and electron microscopy depicted the morphology of NLCs. Caffeine encapsulation efficiency (EE) was measured by UV/Vis spectroscopy. Fourier-transform infrared spectroscopy (FTIR) was applied to show caffeine and NLCs interactions. The caffeine invivo morin model was designed to determine the caffeine penetration into follicles and stratum corneum. 
Results: The optimal formulation consisted of 2% lipid, 2% surfactant, stearic acid/argan oil ratio of 3.5, and span/tween ratio of 1.25. Its spherical NLCs size, PDI, and zeta potential were 256.2 nm, 0.225, and -25.4 respectively. The caffeine EE% was 89% which was homogenously encapsulated in NLCs as shown in FTIR analysis. In vivo studies showed these nanoparticles have the ability to accumulate in the hair follicles by the time. 
Conclusion: The NLC formulation optimized in this study is a potential formulation for intrafollicular delivery of caffeine.


1.    Ajiboye AL, Nandi U, Galli M, Trivedi V. Olanzapine Loaded Nanostructured Lipid Carriers via High Shear Homogenization and Ultrasonication. Sci Pharm. 2021; 89(2): 25.
2.    Ashour A, Hegazy MA, Abdel-Kawy M, ElZeiny MB. Simultaneous spectrophotometric determination of overlapping spectra of paracetamol and caffeine in laboratory prepared mixtures and pharmaceutical preparations using continuous wavelet and derivative transform. Arab J Chem. 2015; 19(2): 186-192.
3.    Bansal M, Manchanda K, Pandey SS. Role of caffeine in the management of androgenetic alopecia. Int J Trichology. 2012; 4(3): 185-186.
4.    Bootz A, Vogel V, Schubert D, Kreuter J. Comparison of scanning electron microscopy, dynamic light scattering and analytical ultracentrifugation for the sizing of poly(butyl cyanoacrylate) nanoparticles. Eur J Pharm Biopharm. 2004; 57(2): 369-375.
5.    Brandner JM, Behne MJ, Huesing B, Moll I. Caffeine improves barrier function in male skin. Int J Cosmet Sci. 2006; 28(5): 343-347.
6.    Daneshmand S, Jaafari mr, Movaffagh J, Malaekeh-nikouei B, Iranshahi M, Seyedian Moghaddam A, et al. Preparation, characterization, and optimization of auraptene-loaded solid lipid nanoparticles as a natural anti-inflammatory agent: In vivo and in vitro evaluations. Colloids Surf B Biointerfaces. 2018; 164.
7.    Daneshmand S, Jaafari MR, Movaffagh J, Malaekeh-Nikouei B, Iranshahi M, Seyedian Moghaddam A, et al. Preparation, characterization, and optimization of auraptene-loaded solid lipid nanoparticles as a natural anti-inflammatory agent: In vivo and in vitro evaluations. Colloids Surf B Biointerfaces. 2018; 164:332-339.
8.    Dorraj G, Moghimi HR. Preparation of SLN-containing Thermoresponsive In-situ Forming Gel as a Controlled Nanoparticle Delivery System and Investigating its Rheological, Thermal and Erosion Behavior. Iran J Pharm Res. 2015; 14(2): 347-358.
9.    Gavazzoni Dias MFR. Hair cosmetics: an overview. Int J Trichology. 2015; 7(1): 2-15.
10.    Gordillo-Galeano A, Mora-Huertas CE. Hydrodynamic diameter and zeta potential of nanostructured lipid carriers: Emphasizing some parameters for correct measurements. Colloids Surf A Physicochem Eng Asp. 2021; 620:126610.
11.    Jafarifar Z, Rezaie M, Sharifan P, Jahani V, Daneshmand S, Ghazizadeh H, et al. Preparation and Characterization of Nanostructured Lipid Carrier (NLC) and Nanoemulsion Containing Vitamin D3. Appl Biochem Biotechnol. 2021.
12.    Jain SK, Verma A, Jain A, Hurkat P. Transfollicular drug delivery: current perspectives. Research and Reports in Transdermal Drug Delivery. 2016: 1.
13.    Jaiswal P, Gidwani B, Vyas A. Nanostructured lipid carriers and their current application in targeted drug delivery. Artif Cells Nanomed Biotechnol. 2016; 44(1): 27-40.
14.    Johnsen E, Brandtzaeg OK, Vehus T, Roberg-Larsen H, Bogoeva V, Ademi O, et al. A critical evaluation of Amicon Ultra centrifugal filters for separating proteins, drugs and nanoparticles in biosamples. J Pharm Biomed Anal. 2016; 120: 106-111.
15.    Knorr F, Lademann J, Patzelt A, Sterry W, Blume-Peytavi U, Vogt A. Follicular transport route – Research progress and future perspectives. Eur J Pharm Biopharm. 2009; 71(2): 173-180.
16.    Kumar R, Singh A, Garg N, Siril PF. Solid lipid nanoparticles for the controlled delivery of poorly water soluble non-steroidal anti-inflammatory drugs. Ultrason Sonochem. 2018; 40:686-896.
17.    Lademann J, Knorr F, Richter H, Jung S, Meinke MC, Rühl E, et al. Hair follicles as a target structure for nanoparticles. J Innov Opt Health Sci. 2014; 08(04): 1530004.
18.    Lizard G, Filali-Zegzouti Y, Midaoui AE. Benefits of Argan Oil on Human Health-May 4-6 2017, Errachidia, Morocco. Int J Mol Sci. 2017; 18(7): 1383.
19.    Löffler H, Dreher F, Maibach HI. Stratum corneum adhesive tape stripping: influence of anatomical site, application pressure, duration and removal. Br J Dermatol. 2004; 151(4): 746-752.
20.    Manchun S, Soradech S, Kingkaew K, Sobharaksha P, Sriamornsak P, Tubtimted S. Design of Caffeine-Loaded Nanostructured Lipid Carriers Containing Coconut Oil for Topical Application. Key Eng Mater. 2019; 819: 187-192.
21.    Mudalige T, Qu H, Van Haute D, Ansar SM, Paredes A, Ingle T. Chapter 11 - Characterization of Nanomaterials: Tools and Challenges. In: López Rubio A, Fabra Rovira MJ, martínez Sanz M, Gómez-Mascaraque LG, editors. Nanomaterials for Food Applications: Elsevier; 2019. p. 313-353.
22.    Otberg N, Patzelt A, Rasulev U, Hagemeister T, Linscheid M, Sinkgraven R, et al. The role of hair follicles in the percutaneous absorption of caffeine. Br J Clin Pharmacol. 2008; 65(4): 488-492.
23.    Patzelt A, Lademann J. Recent advances in follicular drug delivery of nanoparticles. Expert Opin Drug Deliv. 2020; 17(1): 49-60.
24.    Samimi S, Maghsoudnia N, Eftekhari RB, Dorkoosh F. Chapter 3 - Lipid-Based Nanoparticles for Drug Delivery Systems. In: Mohapatra SS, Ranjan S, Dasgupta N, Mishra RK, Thomas S, editors. Characterization and Biology of Nanomaterials for Drug Delivery: Elsevier; 2019. p. 47-76.
25.    Shamma RN, Aburahma MH. Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia. Int J Nanomedicine. 2014; 9: 5449-560.
26.    Shiehzadeh F, Hadizadeh F, Mohammadpour A, Aryan E, Gholami L, Tafaghodi M. Streptomycin sulfate dry powder inhalers for the new tuberculosis treatment schedule. J Drug Deliv Sci Technol. 2019; 52: 957-967.
27.    Shiehzadeh F, Tafaghodi M, Dehghani M-L, Mashhoori F, Fazly Bazzaz BS, Imenshahidi M. Preparation and Characterization of a Dry Powder Inhaler Composed of PLGA Large Porous Particles Encapsulating Gentamicin Sulfate. Adv Pharm Bull. 2019; 9(2): 255-261.
28.    Teichmann A, Jacobi U, Ossadnik M, Richter H, Koch S, Sterry W, et al. Differential Stripping: Determination of the Amount of Topically Applied Substances Penetrated into the Hair Follicles. J Invest Dermatol. 2005; 125(2): 264-269.
29.    Villareal MO, Kume S, Bourhim T, Bakhtaoui FZ, Kashiwagi K, Han J, et al. Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells. Evid Based Complement Alternat Med. 2013; 2013: 340107.
30.    Yu Y-Q, Yang X, Wu X-F, Fan Y-B. Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications. Front Bioeng Biotechnol. 2021; 9(200).