DEVELOPMENT, CHARACTERIZATION, STABILITY AND TOXICITY EVALUATION OF TOPICAL ETHOSOMAL GEL LOADED WITH BERBERIS VULGARIS L. FRUIT EXTRACT AS A COSMECEUTICAL PRODUCT”

Main Article Content

Nayla Javed
Haji Muhammad Shoaib Khan
Naheed Akhtar
Umair Khurshid
Umer Shaukat
Marwah Rehman
Hafiz Arfat Idrees
Muhammad Younus
Muhammad Saleem Qureshi
Zafar Iqbal
Wajeeha Almas
Muhammad Naeem
Rihana Dilshad
Rizwana Dilshad
Muhammad Wajahat
Khadija Karim
Muhammad Shahzad Khan

Keywords

Cosmetic, Berberis vulgaris L., Antioxidant, Nano Ethosomes, Stability testing, Non-invasive in vivo study

Abstract

Berberis vulgaris L. being copious with phenols, flavonoids, alkaloids, and vitamin C along with its value-added organic properties is thought to be a good contender of the cosmetic industry. Study was thus aimed to develop a Berberis vulgaris L. (BV) extract based optimized nano-ethosomal gel and its investigation for skin rejuvenation, acne and hydration effects aided by the increased solubility and trapping of various medicinal agents and plant extract by nanostructured vesicles.


Tyrosinase enzyme inhibition test, phenolic and flavonoid content, and in-vitro SPF (sun protection effect) evaluation of the BV extract were all studied. Zeta size, zeta potential, encapsulation efficiency (%EE), and SEM (scanning electron microscopy) were used to analyse formulations of 09 ethosomal formulations based on BV extract. After being included into the gel system, the skin effects of the improved ethosomal formulation were investigated using minimally invasive in vivo methods. A research on the acute oral toxicity of Berberis vulgaris L. was also conducted to examine any potential harmful effects.


The optimized nano ethosomal formulation (F9) was spherical in shape, 116.5nm in size, −28.5 surface charge, and showed EE 97.38%. The BV loaded ethosomal topical gel was stable physicochemically throughout the study and rheological analysis revealed non-Newtonian behavior. Ex vivo permeation of ethosomal gel exhibited 69.88% release. Statistically ANOVA indicated that in vivo parameter skin effects were significant (P˂.05).


A stable BV loaded nano ethosomal gel system is an inspiring approach for phytoextracts than conventional formulations as a cosmeceutical application that has substantial effects on skin.

Abstract 138 | pdf Downloads 39

References

1. Abdulhamid, A, & Sani, I. (2016). Preliminary phytochemical screening and antimicrobial activity of aqueous and methanolic leave extracts of Balanites aegyptiaca (L.). International Research Journal of Pharmaceutical and Biosciences, 3(1), 1-7.
2. Aggarwal, Divya, & Nautiyal, Ujjwal. (2016). Ethosomes: A review. Int J pharm med res, 4(4), 354-363.
3. Ainbinder, Denize, Godin, Biana, & Touitou, Elka. (2016). Ethosomes: Enhanced delivery of drugs to and across the skin Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement (pp. 61-75): Springer.
4. Antonopoulou, Io, Varriale, Simona, Topakas, Evangelos, Rova, Ulrika, Christakopoulos, Paul, & Faraco, Vincenza. (2016). Enzymatic synthesis of bioactive compounds with high potential for cosmeceutical application. Applied microbiology and biotechnology, 100(15), 6519-6543.
5. Anwar, Fareeha, Saleem, Uzma, Rehman, Atta-Ur, Ahmad, Bashir, Froeyen, Matheus, Mirza, Muhammad Usman, . . . Ahmad, Sarfraz. (2021). Toxicity evaluation of the naphthalen-2-yl 3, 5-dinitrobenzoate: a drug candidate for Alzheimer disease. Frontiers in Pharmacology, 12, 607026.
6. Apone, Fabio, Tito, Annalisa, Carola, Antonietta, Arciello, Stefania, Tortora, Assunta, Filippini, Lucio, . . . Chrispeels, Maarten J. (2010). A mixture of peptides and sugars derived from plant cell walls increases plant defense responses to stress and attenuates ageing-associated molecular changes in cultured skin cells. Journal of biotechnology, 145(4), 367-376.
7. Ascenso, Andreia, Raposo, Sara, Batista, Cátia, Cardoso, Pedro, Mendes, Tiago, Praça, Fabíola Garcia, . . . Simões, Sandra. (2015). Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. International journal of nanomedicine, 10, 5837.
8. Asensio, Esther, Vitales, Daniel, Pérez, Iván, Peralba, Laia, Viruel, Juan, Montaner, Celia, . . . Sales, Ester. (2020). Phenolic Compounds Content and Genetic Diversity at Population Level across the Natural Distribution Range of Bearberry (Arctostaphylos uva-ursi, Ericaceae) in the Iberian Peninsula. Plants, 9(9), 1250.
9. Bansal, Mahima, Reddy, M Sudhakara, & Kumar, Anil. (2017). Optimization of cell growth and bacoside-A production in suspension cultures of Bacopa monnieri (L.) Wettst. using response surface methodology. In Vitro Cellular & Developmental Biology-Plant, 53(6), 527-537.
10. Benzie, Iris FF, & Strain, JJ. (1999). [2] Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration Methods in enzymology (Vol. 299, pp. 15-27): Elsevier.
11. Brandner, JM, & Jensen, JM. (2008). The skin: an indispensable barrier. Exp Dermatol, 17, 1063-1072.
12. Chen, Fu-An, Wu, An-Bang, Shieh, Pochuen, Kuo, Daih-Huang, & Hsieh, Chi-Ying. (2006). Evaluation of the antioxidant activity of Ruellia tuberosa. Food chemistry, 94(1), 14-18.
13. Chourasia, Manish K, Kang, Lifeng, & Chan, Sui Yung. (2011). Nanosized ethosomes bearing ketoprofen for improved transdermal delivery. Results in pharma sciences, 1(1), 60-67.
14. Cichorek, Mirosława, Wachulska, Małgorzata, Stasiewicz, Aneta, & Tymińska, Agata. (2013). Skin melanocytes: biology and development. Advances in Dermatology and Allergology/Postȩpy Dermatologii I Alergologii, 30(1), 30.
15. Costa, Sônia CC, Detoni, Cassia B, Branco, Carla RC, Botura, Mariana B, & Branco, Alexsandro. (2015). In vitro photoprotective effects of Marcetia taxifolia ethanolic extract and its potential for sunscreen formulations. Revista Brasileira de Farmacognosia, 25(4), 413-418.
16. D’Mello, Stacey AN, Finlay, Graeme J, Baguley, Bruce C, & Askarian-Amiri, Marjan E. (2016). Signaling pathways in melanogenesis. International journal of molecular sciences, 17(7), 1144.
17. Dave, Vivek, Kumar, Dhirendra, Lewis, Shaila, & Paliwal, Sarvesh. (2010). Ethosome for enhanced transdermal drug delivery of aceclofenac. International journal of drug delivery, 2(1).
18. Di Mambro, Valéria M, & Fonseca, Maria JV. (2005). Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. Journal of pharmaceutical and biomedical analysis, 37(2), 287-295.
19. Eghbali-Feriz, Samira, Taleghani, Akram, Al-Najjar, Hadi, Emami, Seyed Ahmad, Rahimi, Homa, Asili, Javad, . . . Tayarani-Najaran, Zahra. (2018). Anti-melanogenesis and anti-tyrosinase properties of Pistacia atlantica subsp. mutica extracts on B16F10 murine melanoma cells. Research in pharmaceutical sciences, 13(6), 533.
20. Elsayed, Mustafa MA, Abdallah, Ossama Y, Naggar, Viviane F, & Khalafallah, Nawal M. (2007). Lipid vesicles for skin delivery of drugs: reviewing three decades of research. International journal of pharmaceutics, 332(1-2), 1-16.
21. Espinosa-Leal, Claudia A, & Garcia-Lara, Silverio. (2019). Current methods for the discovery of new active ingredients from natural products for cosmeceutical applications. Planta médica, 85(07), 535-551.
22. Fouladi, Rohollah F. (2012). Aqueous extract of dried fruit of Berberis vulgaris L. in acne vulgaris, a clinical trial. Journal of dietary supplements, 9(4), 253-261.
23. Fu, Rao, Zhang, Yuting, Guo, Yiran, & Chen, Fang. (2014). Antioxidant and tyrosinase inhibition activities of the ethanol-insoluble fraction of water extract of Sapium sebiferum (L.) Roxb. leaves. South African Journal of Botany, 93, 98-104.
24. Gajardo, Sandra, Aguilar, Marilú, Stowhas, Tamara, Salas, Felipe, Lopez, José, Quispe, Cristina, . . . Benites, Julio. (2016). Determination of sun protection factor and antioxidant properties of six Chilean Altiplano plants. Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 15(5), 352-363.
25. Gaspar, LR, & Campos, PMBG Maia. (2003). Rheological behavior and the SPF of sunscreens. International journal of pharmaceutics, 250(1), 35-44.
26. Ghribia, Lotfi, Ghouilaa, Hatem, Omrib, Amel, Besbesb, Malek, & Janneta, Hichem Ben. (2014). Antioxidant and anti–acetylcholinesterase activities of extracts and secondary metabolites from Acacia cyanophylla. Asian Pacific journal of tropical biomedicine, 4, S417-S423.
27. Gilbert, Laura, Picard, Céline, Savary, Géraldine, & Grisel, Michel. (2013). Rheological and textural characterization of cosmetic emulsions containing natural and synthetic polymers: relationships between both data. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 421, 150-163.
28. Hadaruga, Daniel I, Hadaruga, Nicoleta G, Bandur, Geza N, Rivis, Adrian, Costescu, Corina, Ordodi, Valentin L, & Ardelean, Aurel. (2010). Berberis vulgaris extract/β cyclodextrin nanoparticles synthesis and characterization. Rev Chim (Bucharest), 61, 669-675.
29. Hameed, Abdul, Akhtar, Naveed, Khan, Haji Muhammad Shoaib, & Asrar, Muhammad. (2019). Skin sebum and skin elasticity: Major influencing factors for facial pores. Journal of cosmetic dermatology, 18(6), 1968-1974.
30. Iizhar, Syed Ahmed, Syed, Ismail Ahmed, Satar, Rukhsana, & Ansari, Shakeel Ahmed. (2016). In vitro assessment of pharmaceutical potential of ethosomes entrapped with terbinafine hydrochloride. Journal of advanced research, 7(3), 453-461.
31. Ijaz, Musarrat, & Akhtar, Naveed. (2020). Fatty acids based α‐Tocopherol loaded nanostructured lipid carrier gel: In vitro and in vivo evaluation for moisturizing and anti‐aging effects. Journal of cosmetic dermatology, 19(11), 3067-3076.
32. Ijaz, Shakeel, Khan, Haji Muhammad Shoaib, Anwar, Zeeshan, Talbot, Brian, & Walsh, John J. (2019). HPLC profiling of Mimosa pudica polyphenols and their non-invasive biophysical investigations for anti-dermatoheliotic and skin reinstating potential. Biomedicine & Pharmacotherapy, 109, 865-875.
33. Imanshahidi, Mohsen, & Hosseinzadeh, Hossein. (2008). Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytotherapy research, 22(8), 999-1012.
34. Jain, S, Umamaheshwari, RB, Bhadra, D, & Jain, NK. (2004). Ethosomes: a novel vesicular carrier for enhanced transdermal delivery of an antiHIV agent. Indian journal of pharmaceutical sciences, 66(1), 72.
35. Kamtekar, Samidha, Keer, Vrushali, & Patil, Vijaya. (2014). Estimation of phenolic content, flavonoid content, antioxidant and alpha amylase inhibitory activity of marketed polyherbal formulation. Journal of applied pharmaceutical Science, 4(9), 61.
36. Khan, Palwasha, & Akhtar, Naveed. (2022). Phytochemical investigations and development of ethosomal gel with Brassica oleraceae L.(Brassicaceae) extract: An innovative nano approach towards cosmetic and pharmaceutical industry. Industrial Crops and Products, 183, 114905.
37. Khan, Palwasha, Akhtar, Naveed, Khan, Haji Muhammad Shoaib, Tasneem, Rabia, Zaka, Hafiz Saqib, Akhtar, Naheed, & Sharif, Arfa. (2022). Assessment of Brassica oleraceae L.(Brassicaceae) Extract loaded Ethosomal gel as a versatile Vesicular carrier system for Dermocosmetic application: A noninvasive split‐faced study. Journal of Cosmetic Dermatology.
38. Končić, M Zovko, Kremer, Dario, Karlović, Ksenija, & Kosalec, Ivan. (2010). Evaluation of antioxidant activities and phenolic content of Berberis vulgaris L. and Berberis croatica Horvat. Food and chemical toxicology, 48(8-9), 2176-2180.
39. Korkina, Liudmila G, Mayer, Wolfgang, & De Luca, Chiara. (2017). Meristem plant cells as a sustainable source of redox actives for skin rejuvenation. Biomolecules, 7(2), 40.
40. Lee, Sang Yeul, Baek, Namhuk, & Nam, Tae-gyu. (2016). Natural, semisynthetic and synthetic tyrosinase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(1), 1-13.
41. Lopez-Pinto, JM, Gonzalez-Rodriguez, ML, & Rabasco, AM. (2005). Effect of cholesterol and ethanol on dermal delivery from DPPC liposomes. International journal of pharmaceutics, 298(1), 1-12.
42. Maia, Juliana Leão, Dantas, Thayse Naianne Pires, Neto, Bento Pereira da Costa, Borges, Kátia Cristina, Lima, Erica Cortez, da Mata, Ana Lúcia de Medeiros Lula, . . . Pereira, Camila Gambini. (2019). Extract of spray‐dried Malay apple (Syzygium malaccense L.) skin. Journal of Food Process Engineering, 42(8), e13275.
43. Manosroi, Aranya, Jantrawut, Pensak, Akihisa, Toshihiro, Manosroi, Worapaka, & Manosroi, Jiradej. (2011). In vitro and in vivo skin anti-aging evaluation of gel containing niosomes loaded with a semi-purified fraction containing gallic acid from Terminalia chebula galls. Pharmaceutical biology, 49(11), 1190-1203.
44. Maurya, Sheo Datta, Prajapati, S, Gupta, A, Saxena, G, & Dhakar, Ram Chand. (2010). Formulation development and evaluation of ethosome of stavudine. Int J Pharm Edu Res, 13, 16.
45. Mukherjee, Pulok K, Maity, Niladri, Nema, Neelesh K, & Sarkar, Birendra K. (2011). Bioactive compounds from natural resources against skin aging. Phytomedicine, 19(1), 64-73.
46. Nasrollahzadeh, Mahmoud, Maham, Mehdi, Rostami-Vartooni, Akbar, Bagherzadeh, Mojtaba, & Sajadi, S Mohammad. (2015). Barberry fruit extract assisted in situ green synthesis of Cu nanoparticles supported on a reduced graphene oxide–Fe 3 O 4 nanocomposite as a magnetically separable and reusable catalyst for the O-arylation of phenols with aryl halides under ligand-free conditions. RSC advances, 5(79), 64769-64780.
47. Nawaz, Mehwish, Khan, Haji Muhammad Shoaib, Akhtar, Naveed, Jamshed, Talha, Qaiser, Rubina, Shoukat, Hina, & Farooq, Mehrin. (2019). Photodamage and Photoprotection: An In vivo Approach Using Noninvasive Probes. Photochemistry and photobiology, 95(5), 1243-1248.
48. Ovaere, Petra, Lippens, Saskia, Vandenabeele, Peter, & Declercq, Wim. (2009). The emerging roles of serine protease cascades in the epidermis. Trends in biochemical sciences, 34(9), 453-463.
49. Özgen, Mustafa, Saraçoğlu, Onur, & Geçer, Esma Nur. (2012). Antioxidant capacity and chemical properties of selected barberry (Berberis vulgaris L.) fruits. Horticulture, Environment, and Biotechnology, 53(6), 447-451.
50. Rahimi-Madiseh, Mohammad, Lorigoini, Zahra, Zamani-Gharaghoshi, Hajar, & Rafieian-Kopaei, Mahmoud. (2017). Berberis vulgaris: specifications and traditional uses. Iranian Journal of Basic Medical Sciences, 20(5), 569.
51. Rakesh, R, & Anoop, KR. (2012). Ethosomes for transdermal and topical drug delivery. Int J Pharm Pharm Sci, 4(3), 17-24.
52. Ramadon, Delly, Goldie, Aisha Wirarti, & Anwar, Effionora. (2017). Novel transdermal ethosomal gel containing green tea (Camellia sinensis L. Kuntze) leaves extract: formulation and in vitro penetration study. Journal of Young Pharmacists, 9(3), 336.
53. Rathapon, A, Sirivat, Anuvat, & Vayumhasuwan, Panida. (2005). Viscoelastic properties of Carbopol 940 gels and their relationships to piroxicam diffusion coefficients in gel bases. Pharmaceutical Research, 22(12), 2134-2140.
54. Saewan, Nisakorn, Vichit, Wannisa, & Prinyarux, Thanon. (2018). Anti-aging efficacy of Thai red rice callus cosmetic product. The Journal of Applied Science, 17(Special), 63-72.
55. Saini, NK, Singhal, M, & Srivastava, B. (2011). Evaluation of antioxidant activity of Tecomaria capensis leaves extract. Inventi Rapid Ethnopharmacol, 2011(2), 117.
56. Samnani, A, Shahwal, V, Bhowmick, M, Joshi, A, & Dubey, BK. (2012). Design and evaluation of ultradeformable soft elastic nano vesicle ethosomes for dermal delivery. Int J Biomed Adv Res, 3(02), 111-117.
57. Sayre, Robert M, Agin, Patricia Poh, LeVee, Gordon J, & Marlowe, Edward. (1979). A comparison of in vivo and in vitro testing of sunscreening formulas. Photochemistry and Photobiology, 29(3), 559-566.
58. Shahwar, Durre, Ullah, Saif, Ahmad, Mobasher, Ullah, Sami, Ahmad, Naeem, & AKMAL, KHAN MUHAMMAD. (2011). Hypoglycemic activity of Ruellia tuberosa linn (Acanthaceae) in normal and alloxan-induced diabetic rabbits.
59. Srivastava, N, Singh, K, & Amrit, K. (2015). Formulation and evaluation of seabuckthorn leaf extract loaded ethosomal gel. Asian J Pharm Clin Res, 8, 316-320.
60. Surini, Silvia, Arnedy, Antik R, & Iswandana, Raditya. (2019). Development of Ethosome Containing Bitter Melon (Momordica charantia Linn.) Fruit Fraction and In Vitro Skin Penetration. Pharmacognosy Journal, 11(6).
61. Tabeshpour, Jamshid, Imenshahidi, Mohsen, & Hosseinzadeh, Hossein. (2017). A review of the effects of Berberis vulgaris and its major component, berberine, in metabolic syndrome. Iranian journal of basic medical sciences, 20(5), 557.
62. Touitou, E, Dayan, N, Bergelson, L, Godin, Biana, & Eliaz, M. (2000). Ethosomes—novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. Journal of controlled release, 65(3), 403-418.
63. Touitou, E, Godin, Biana, Dayan, N, Weiss, C, Piliponsky, A, & Levi-Schaffer, F. (2001). Intracellular delivery mediated by an ethosomal carrier. Biomaterials, 22(22), 3053-3059.
64. Upadhyay, Tarun K, Fatima, Nida, Sharma, Deepak, Saravanakumar, V, & Sharma, Rolee. (2017). Preparation and characterization of beta-glucan particles containing a payload of nanoembedded rifabutin for enhanced targeted delivery to macrophages. EXCLI journal, 16, 210.
65. Uttra, Ambreen Malik, & Hasan, Umme Habiba. (2017). Anti-arthritic activity of aqueous-methanolic extract and various fractions of Berberis orthobotrys Bien ex Aitch. BMC complementary and alternative medicine, 17(1), 1-16.
66. Venus, Matt, Waterman, Jacqueline, & McNab, Ian. (2010). Basic physiology of the skin. Surgery (Oxford), 28(10), 469-472.
67. Verma, Poonam, & Pathak, K. (2010). Therapeutic and cosmeceutical potential of ethosomes: An overview. Journal of advanced pharmaceutical technology & research, 1(3), 274.
68. Videira, Inês Ferreira dos Santos, Moura, Daniel Filipe Lima, & Magina, Sofia. (2013). Mechanisms regulating melanogenesis. Anais brasileiros de dermatologia, 88, 76-83.
69. Wan, Miaojian, Hu, Rong, Xie, Xiaoyuan, Gong, Zijian, Yi, Jinling, Chen, Haiyan, . . . Lai, Wei. (2017). Skin erythema, pigmentation and hydration kinetics after ultraviolet radiation‐induced photodamage in southern chinese women. Photochemistry and photobiology, 93(5), 1276-1281.
70. Yamaguchi, Yuji, & Hearing, Vincent J. (2009). Physiological factors that regulate skin pigmentation. Biofactors, 35(2), 193-199.
71. Zhang, Zhen, Wo, Yan, Zhang, Yixin, Wang, Danru, He, Rong, Chen, Huijin, & Cui, Daxiang. (2012). In vitro study of ethosome penetration in human skin and hypertrophic scar tissue. Nanomedicine: Nanotechnology, Biology and Medicine, 8(6), 1026-1033.
72. Zhishen, J, Mengcheng, T, & Jianming, W. (1999). Research on antioxidant activity of flavonoids from natural materials. Food Chem, 64, 555-559.

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