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Sains Malaysiana 52(6)(2023):
http://doi.org/10.17576/jsm-2023-5206-05
Activity and
Safety of Cinchonine Nanostructured Lipid Carriers as a Hair Growth Stimulant
in Mice Model of Androgenetic Alopecia
(Aktiviti dan Keselamatan Pembawa Lipid Berstruktur
Nano Sinkonina sebagai Perangsang Pertumbuhan Rambut dalam Model Tikus Alopecia
Androgenetik)
HARIYANTI
HARIYANTI1,2, RACHMAT MAULUDIN1, YEYET CAHYATI
SUMIRTAPURA1 & NENG FISHERI KURNIATI3*
1Department of Pharmaceutic,
School of Pharmacy, Institut Teknologi Bandung, Bandung, West Java, 40132,
Indonesia
2Department of Pharmaceutical, Faculty of Pharmacy,
Universitas Muhammadiyah Purwokerto, Purwokerto, Central Java, 53182,
Indonesia
3Department of Pharmacology-Clinical Pharmacy, School
of Pharmacy, Institut Teknologi Bandung, Bandung, West Java, 40132, Indonesia
Received: 21 February 2022/Accepted: 9 June 2023
Abstract
Androgenetic
alopecia (AA) is a hair growth disorder characterized by hair loss and
miniaturization of the size of follicles and dermal papillae. Cinchonine is a
quinoline alkaloid that can increase VEGF production and potential as a hair
growth stimulant. This study aimed to determine the morphology, penetration (in
vitro), as well as safety and activity of cinchonine nanostructured lipid
carriers (CN-NLC) serum as a hair growth stimulant. Preparation of CN-NLC serum
using a combination of micro-emulsification and ultra-sonification methods,
characterization of CN-NLC serum included morphology and closed hair follicle
diffusion methods.
Dermal and eye irritation test using New Zealand rabbit strain with primary
irritation index parameters. Hair growth stimulant activity test using Swiss
Webster mice strain, induced with the hormone testosterone. Observations were
performed at 7, 14, and 21 days with hair length and histology parameters.
CN-NLC serum morphology is a spherical shape with size ±500 nm, diffusion of
serum CN-NLC (open hair follicles) of 23.92±0.84%; (close hair follicles) of
11.37±2.29%; and CN solution of 6.00±0.72%. CN-NLC serum are non-irritant with
a primary irritation index of 0.0. Activity tests showed hair length on days 7;
14 and 21 were increased by 20.24-23.74%; 33.47-36.43%, and 39.30-39.97%
(P≤0.05). Histological data showed an increase in the number and size of
both dermal papillae and hair follicles compared to the control group. CN-NLC
serum can improve the penetration of CN into hair follicles. CN-NLC serum is
safe and effective as a hair growth stimulant in the treatment of AA.
Keywords: Androgenic alopecia; cinchonine; nanostructured lipid
carriers
Abstrak
Alopecia
androgenetik (AA) adalah gangguan pertumbuhan rambut yang dicirikan oleh
keguguran rambut dan pengecilan saiz folikel dan papila dermal. Sinkonina
adalah alkaloid kuinolina yang boleh meningkatkan pengeluaran VEGF dan
berpotensi sebagai perangsang pertumbuhan rambut. Kajian ini bertujuan untuk
menentukan morfologi, penembusan (in vitro), serta keselamatan dan
aktiviti serum pembawa lipid berstruktur nano (CN-NLC) sinkonina sebagai
perangsang pertumbuhan rambut. Penyediaan serum CN-NLC menggunakan gabungan
kaedah pengemulsi mikro dan ultra-sonifikasi, pencirian serum CN-NLC termasuk
kaedah morfologi dan kaedah penyebaran folikel rambut tertutup. Ujian
kerengsaan kulit dan mata menggunakan ketegangan arnab New Zealand dengan
parameter indeks kerengsaan primer. Ujian aktiviti perangsang pertumbuhan
rambut menggunakan ketegangan tikus Swiss Webster, diinduksi dengan hormon
testosteron. Pemerhatian dilakukan pada 7, 14 dan 21 hari dengan panjang rambut
dan parameter histologi. Morfologi serum CN-NLC ialah bentuk sfera dengan saiz
±500 nm, resapan serum CN-NLC (folikel rambut terbuka) sebanyak 23.92±0.84%;
(folikel rambut tertutup) sebanyak 11.37±2.29%; dan larutan CN sebanyak
6.00±0.72%. Serum CN-NLC tidak merengsa dengan indeks kerengsaan primer 0.0.
Ujian aktiviti menunjukkan panjang rambut pada hari ke-7; 14 dan 21 meningkat
sebanyak 20.24-23.74%; 33.47-36.43% dan 39.30-39.97% (P≤0.05). Data
histologi menunjukkan peningkatan dalam bilangan dan saiz kedua-dua papila
dermal dan folikel rambut berbanding kumpulan kawalan. Serum CN-NLC dapat
meningkatkan penembusan CN ke dalam folikel rambut. Serum CN-NLC selamat dan
berkesan sebagai perangsang pertumbuhan rambut dalam rawatan AA.
Kata
kunci: Alopecia androgenetik; pembawa lipid berstruktur nano; sinkonina
REFERENCES
Abd,
E., Benson, H.A.E., Roberts, M.S. & Grice, J.E. 2018. Follicular
penetration of caffeine from topically applied nanoemulsion formulations
containing penetration enhancers: in vitro human skin studies. Skin
Pharmacology and Physiology 31(5): 252-260. https://doi.org/10.1159/000489857
Blume-Peytavi, U., Varvar, K. & Vogt, A. 2016. The
Alopecias Diagnosis and Treatments, edited by Bouhanna, P. & Bouhanna,
E. Boca Raton: CRC Press.
Blume-Peytavi,
U., Tosti, A., Whiting, D.A. & Trüeb, R.M. 2008. Hair Growth and
Disorders. Hair. Springer. https://doi.org/10.1007/978-3-540-46911-7
Bubić
Pajić, N., Ilić, T., Nikolić, I., Dobričić, V.,
Pantelić, I. & Savić, S. 2019. Alkyl Polyglucoside-Based
Adapalene-Loaded Microemulsions for Targeted Dermal Delivery: Structure,
Stability and Comparative Biopharmaceutical Characterization with a
Conventional Dosage Form. Journal of Drug Delivery Science and Technology 54. https://doi.org/10.1016/j.jddst.2019.101245
Chen,
Y., Feng, X., Zhao, Y., Zhao, X. & Zhang, X. 2020. Mussel-inspired
polydopamine coating enhances the intracutaneous drug delivery from
nanostructured lipid carriers dependently on a follicular pathway. Molecular
Pharmaceutics 17(4): 1215-1225.
https://doi.org/10.1021/acs.molpharmaceut.9b01240
Driskell,
R.R., Clavel, C., Rendl, M. & Watt, F.M. 2011. Hair follicle dermal papilla
cells at a glance. Journal of Cell Science 124(8): 1179-1182.
https://doi.org/10.1242/jcs.082446
Fresta,
M., Mancuso, A., Cristiano, M.C., Urbanek, K., Cilurzo, F., Cosco, D., Iannone,
M. & Paolino, D. 2020. Targeting of the pilosebaceous follicle by liquid
crystal nanocarriers: in vitro and in vivo effects of the
entrapped minoxidil. Pharmaceutics 12(11): 1127.
https://doi.org/10.3390/pharmaceutics12111127.
Fu,
D., Huang, J., Li, K., Chen, Y., He, Y., Sun, Y., Guo, Y., Du, L., Qu, Q.,
Miao, Y. & Hu, Z. 2021. Dihydrotestosterone-induced hair regrowth
inhibition by activating androgen receptor in C57BL6 mice simulates
androgenetic alopecia. Biomedicine and Pharmacotherapy 137: 111247.
https://doi.org/10.1016/j.biopha.2021.111247
Gorzelanny,
C., Mess, C., Schneider, S.W., Huck, V. & Brandner, J.M. 2020. Skin
barriers in dermal drug delivery: Which barriers have to be overcome and how
can we measure them? Pharmaceutics. https://doi.org/10.3390/pharmaceutics12070684
Hariyanti,
H., Sophi Damayanti & Sasanti Tarini Darijanto. 2020. Formulation and
Activity test of cinchonine niosomesas hair growth stimulants. In EBSCO
Industries, Inc. Vol. Suppl, p. 47.
Hariyanti,
H., Kurniati, N.F., Sumirtapura, Y.C. & Mauludin, R. 2023. Development and
validation of an analytical method for the determination of nanostructured
lipid carrier’s cinchonine used direct method modified by liquid-liquid
extraction using high-performance liquid chromatography. Journal of Research
in Pharmacy 27(2): 913-923. https://doi.org/10.29228/jrp.371
Hariyanti,
H., Mauludin, R., Sumirtapura, Y.C. & Kurniati, N.F. 2022. A review:
Pharmacological activities of quinoline alkaloid of Cinchona sp. Biointerface
Research in Applied Chemistry 13(Issue 4): 3.
https://doi.org/org/10.33263/BRIAC134.319
Inaba,
M. & Inaba, Y. 1996. Therapy for androgenetic alopecia. In Androgenetic
Alopecia. Tokyo: Springer. https://doi.org/10.1007/978-4-431-67038-4_25.
Jeong,
G., Shin, S.H., Kim, S.N., Na, Y., Park, B.C., Cho, J.H., Park, W-S. & Kim,
H-J. 2022. Ginsenoside Re Prevents 3-Methyladenine-induced catagen phase
acceleration by regulating Wnt/β-catenin signaling in human dermal papilla
cells. Journal of Ginseng Research 47(3): 440-447. https://doi.org/https://doi.org/10.1016/j.jgr.2022.11.002
Jimenez,
W., Gonzalez, E., Murphy, V.A. & Bauta, W. 2021. Evaluation of dermal
corrosion and irritation by cytoreg in rabbits. Toxicology Reports 8:
1527-1529. https://doi.org/10.1016/j.toxrep.2021.07.021
Joshi,
M.D., Prabhu, R.H. & Patravale, V.B. 2019. Fabrication of nanostructured
lipid carriers (NLC)-based gels from microemulsion template for delivery
through skin. In Methods in Molecular Biology 2000: 279-292.
https://doi.org/10.1007/978-1-4939-9516-5_19
Kakadia,
P.G. & Conway, B.R. 2018. Solid lipid nanoparticles for targeted delivery
of triclosan into skin for infection prevention. Journal of
Microencapsulation 35(7-8): 695-704.
https://doi.org/10.1080/02652048.2019.1576796
Kharat,
M. & McClements, D.J. 2019. Fabrication and characterization of
nanostructured lipid carriers (NLC) using a plant-based emulsifier: Quillaja
Saponin. Food Research International 126: 108601.
https://doi.org/10.1016/j.foodres.2019.108601
Kim,
J.H., Na, J., Bak, D‑H., Lee, B.C., Lee, E., Choi, M.J., Ryu, C.H., Lee,
S., Mun, S.K., Park, B.C., Kim, B.J. & Lee, H.S. 2019a. Development of
Finasteride Polymer Microspheres for Systemic Application in Androgenic
Alopecia. International Journal of Molecular Medicine 43(6): 2409-2419.
https://doi.org/10.3892/ijmm.2019.4149
Kim,
M.H., Kim, K.T., Sohn, S.Y., Lee, J.Y., Lee, C.H., Yang, H., Lee, B.K., Lee,
K.W. & Kim, D.D. 2019b. Formulation and evaluation of nanostructured lipid
carriers (NLCs) of 20(s)-protopanaxadiol (PPD) by box-behnken design. International
Journal of Nanomedicine 14: 8509-8520. https://doi.org/10.2147/IJN.S215835.
Kim,
S.H., Park, M.K., Seol, J.K., Im, J.M., Park, H.S., Seo, H.S., Park, H.J. &
Nah, S.S. 2021. Evaluation of potential eye or skin irritation/corrosion in
rabbit exposed to Tio2 photocatalyst (GST). Environmental Health
and Toxicology 36(3): e2021022-0. https://doi.org/10.5620/eaht.2021022
Lademann,
J., Darvin, M.E., Meinke, M.C. & Patzelt, A. 2019. Characterization of
penetration of particles after dermal application. In Nanocosmetics,
edited by Cornier, J., Keck, C., van de Voorde, M. Springer, Cham.
https://doi.org/10.1007/978-3-030-16573-4_11
Lademann,
J., Knorr, F., Richter, H., Jung, S., Meinke, M.C., Rühl, E., Alexiev, U.,
Calderon, M. & Patzelt, A. 2015. Hair follicles as a target structure for
nanoparticles. Journal of Innovative Optical Health Sciences 8(4):
1530004. https://doi.org/10.1142/S1793545815300049
Lademann,
J., Richter, H., Teichmann, A., Otberg, N., Blume-Peytavi, U., Luengo, J.,
Weiss, B., Schaefer, U.F., Lehr, C-M., Wepf, R. & Sterry, W. 2007.
Nanoparticles - An efficient carrier for drug delivery into the hair follicles. European Journal of Pharmaceutics and Biopharmaceutics 66(2): 159-164. https://doi.org/10.1016/j.ejpb.2006.10.019
Leveque,
M., Mas, C., Haure, M., Lejeune, O., Duplan, H., Castex-Rizzi, N. &
Bessou-Touya, S. 2021. 601 hair growth properties of Cinchona succirubra extract, Leontopodium alpinum extract and manganese pca in human hair
follicle dermal papilla cells. Journal of Investigative Dermatology 141(5): S104. https://doi.org/10.1016/j.jid.2021.02.629
Melincovici,
C.S., Boşca, A.B., Şuşman, S., Mărginean, M., Mihu, C.,
Istrate, M., Moldovan, I.M., Roman, A.L. & Mihu, C.M. 2018. Vascular
endothelial growth factor (VEGF) - Key factor in normal and pathological
angiogenesis. Romanian Journal of Morphology and Embryology 59(2):
455-467.
Mohd,
F., Todo, H., Yoshimoto, M., Eddy Yusuf & Sugibayashi, K. 2016.
Contribution of the hair follicular pathway to total skin permeation of
topically applied and exposed chemicals. Pharmaceutics 8(4): 32.
https://doi.org/10.3390/pharmaceutics8040032
Ou,
H.C., Keating, S., Wu, P., Simon, J.A., Raible, D.W. & Rubel, E.W. 2012.
Quinoline ring derivatives protect against aminoglycoside-Induced hair cell
death in the zebrafish lateral line. JARO - Journal of the Association for
Research in Otolaryngology 13(6): 759-770.
https://doi.org/10.1007/s10162-012-0353-0
Patzelt,
A. & Lademann, J. 2020. Recent advances in follicular drug delivery of
nanoparticles. Expert Opinion on Drug Delivery 17(1): 49-60. https://doi.org/10.1080/17425247.2020.1700226.
Pereira,
M.N., Tolentino, S., Pires, F.Q., Anjos, J.L.V., Alonso, A., Gratieri, T.,
Cunha-Filho, M. & Gelfuso, G.M. 2021. Nanostructured lipid carriers for
hair follicle-targeted delivery of clindamycin and rifampicin to hidradenitis
suppurativa treatment. Colloids and Surfaces B: Biointerfaces 197:
111448. https://doi.org/10.1016/j.colsurfb.2020.111448
Pires,
F.Q., da Silva, J.K.R., Sa-Barreto, L.L., Gratieri, T., Gelfuso, G.M. &
Cunha-Filho, M. 2019. Lipid nanoparticles as carriers of cyclodextrin inclusion
complexes: A promising approach for cutaneous delivery of a volatile essential
oil. Colloids and Surfaces B: Biointerfaces 182: 110382.
https://doi.org/10.1016/j.colsurfb.2019.110382
Rooney,
J.P., Choksi, N.Y., Ceger, P., Daniel, A.B., Truax, J., Allen, D. &
Kleinstreuer, N. 2021. Analysis of variability in the rabbit skin irritation
assay. Regulatory Toxicology and Pharmacology 122: 104920.
https://doi.org/10.1016/j.yrtph.2021.104920
Santos,
G.A., Angelo, T., Andrade, L.M., Silva, S.M.M., Magalhães, P.O., Cunha-Filho,
M., Gelfuso, G.M., Taveira, S.F. & Gratieri, T. 2018. The role of
formulation and follicular pathway in voriconazole cutaneous delivery from
liposomes and nanostructured lipid carriers. Colloids and Surfaces B:
Biointerfaces 170: 341-346. https://doi.org/10.1016/j.colsurfb.2018.06.037
Santos,
A.C., Pereira-Silva, M., Guerra, C., Costa, D., Peixoto, D., Pereira, I., Pita,
I., Ribeiro, A.J. & Veiga, F. 2020. Topical minoxidil-Loaded nanotechnology
strategies for alopecia. Cosmetics 7(2): 21.
https://doi.org/10.3390/COSMETICS7020021
Satheeshan,
K.N., Seema, B.R. & Manjusha, M.A.V. 2020. Development and evaluation of
VCO based herbal hair tonic. Journal of Pharmacognosy and Phytochemistry 9(2): 485-493.
https://www.phytojournal.com/archives/2020/vol9issue3/PartH/9-3-5-112.pdf
Souto,
E. 2004. Development of a controlled release formulation based on SLN and NLC
for topical clotrimazole delivery. International Journal of Pharmaceutics 278(1): 71-77. https://doi.org/10.1016/s0378-5173(04)00153-x
Taghiabadi,
E., Nilforoushzadeh, M.A. & Aghdami, N. 2020. Maintaining hair inductivity
in human dermal papilla cells: A review of effective methods. Skin
Pharmacology and Physiology 33(5): 280-292.
https://doi.org/10.1159/000510152
Tanaka,
S., Saito, M. & Tabata, M. 1980. Bioassay of crude drugs for hair growth
promoting activity in mice by a new simple method. Planta Medica 40(Suppl.): 84-90. https://doi.org/10.1055/s-2008-1075009
Todo,
H. & Mohd. F. 2017. Related topic: Drug permeation through hair follicles.
In Skin Permeation and Disposition of Therapeutic and Cosmeceutical
Compounds, edited by Sugibayashi, K. Tokyo: Springer. pp. 399-409.
https://doi.org/10.1007/978-4-431-56526-0_36
Toll,
R., Jacobi, U., Richter, H., Lademann, J., Schaefer, H. & Blume-Peytavi, U.
2004. Penetration profile of microspheres in follicular targeting of terminal
hair follicles. Journal of Investigative Dermatology 123(1): 168-176.
https://doi.org/10.1111/j.0022-202X.2004.22717.x
Truong,
V.L., Bak, M.J., Lee, C., Jun, M. & Jeong, W.S. 2017. Hair regenerative
mechanisms of red ginseng oil and its major components in the
testosterone-induced delay of anagen entry in C57BL/6 mice. Molecules 22(9): 1505. https://doi.org/10.3390/molecules22091505.
Vanhoutte,
P.M., Zhao, Y., Xu, A. & Leung, S.W.S. 2016. Thirty years of saying NO:
Sources, fate, actions, and misfortunes of the endothelium-derived vasodilator
mediator. Circulation Research 119(2): 375-396.
https://doi.org/10.1161/CIRCRESAHA.116.306531.
Vitorino,
C., Sousa, J. & Pais, A. 2015. Overcoming the skin permeation barrier:
Challenges and opportunities. Current Pharmaceutical Design 21(20):
2698-2712. https://doi.org/10.2174/1381612821666150428124053.
Wang,
Z.D., Feng, Y., Sun, L., Gan, J., Li, X., Ding, W.F. & Chen, X.M. 2021.
Anti-androgenetic alopecia effect of policosanol from chinese wax by regulating
abnormal hormone levels to suppress premature hair follicle entry into the
regression phase. Biomedicine and Pharmacotherapy 136: 111241.
https://doi.org/10.1016/j.biopha.2021.111241
Wang,
Z.D., Feng, Y., Ma, L.Y., Li, X., Ding, W.F. & Chen, X.M. 2017. Hair growth
promoting effect of white wax and policosanol from white wax on the mouse model
of testosterone-induced hair loss. Biomedicine and Pharmacotherapy 89:
438-446. https://doi.org/10.1016/j.biopha.2017.02.036
Yazdani-Arazi,
S.N., Ghanbarzadeh, S., Adibkia, K., Kouhsoltani, M. & Hamishehkar, H.
2017. Histological evaluation of follicular delivery of arginine via
nanostructured lipid carriers: A novel potential approach for the treatment of
alopecia. Artificial Cells, Nanomedicine and Biotechnology 45(7):
1379-1387. https://doi.org/10.1080/21691401.2016.1241794
Yokouchi,
M. & Kubo, A. 2018. Maintenance of tight junction barrier integrity in cell
turnover and skin diseases 27(8): 876-883. Experimental Dermatology https://doi.org/10.1111/exd.13742
Zhang,
B., Zhang, R.W., Yin, X.Q., Lao, Z.Z., Zhang, Z., Wu, Q.G., Yu, L.W., Lai,
X.P., Wan, Y.H. & Li, G. 2016. Inhibitory activities of some traditional
Chinese herbs against testosterone 5α-reductase and effects of Cacumen
platycladi on hair re-growth in testosterone-treated mice. Journal of
Ethnopharmacology 177: 1-9. https://doi.org/10.1016/j.jep.2015.11.012.
*Corresponding
author; email: nfkurniati@fa.itb.ac.id
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