• MARWA ABDALLAH National Organization of Drug Control and Research, Pharmaceutics Department, Egypt
  • DEMIANA I. NESEEM National Organization of Drug Control and Research, Pharmaceutics Department, Egypt
  • OMAIMA N. ELGAZAYERLY Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
  • ALY A. ABDELBARY Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt, School of Life and Medical Sciences, University of Hertfordshire hosted by Global Academic Foundation, Cairo, Egypt



Quercetin, Transfersomes, Wound treatment, Topical formulation


Objective: To design topical Quercetin (Qc)-loaded transfersomes (TFs) for wound treatment.

Methods: Qc-loaded TFs were prepared by thin-film hydration technique using 2241full factorial design and the optimum formula was selected. In vivo skin, deposition and cutaneous wound induction studies were performed for four groups of male wistar rats. At the end of the experiment, biochemical parameters were measured in the healed tissues (total proteins (TP), total antioxidant capacity (TAC), glutathione reductase (GSH), nitric oxide (NO), and malonaldehyde (MDA). Two in vivo histopathological experiments using male wistar rats were performed; the first study was done for the healed tissues of the above experiment and the second was to confirm the safety of formulations.

Results: Qc optimum TFs (F6) showed EE% of 91.1%, PS of 695.35 nm, PDI of 0.592, and ZP of-11.1 mV, and spherical shape. In vivo skin deposition study showed that drug percentage retained in the skin from Qc optimum TFs was significantly higher than that from Qc suspension and Qc liposomes (p<0.05). There was no significant difference in the values of TP, TAC and MDA between the treated groups (p>0.05). GSH in TFs treated groups was significantly higher than the other groups (p<0.05) while NO in TFs treated groups was significantly lower than the other treated groups (p<0.05). Histopathological experiments showed that wounds treated by TFs healed better than those treated by both liposomes and Qc suspension.

Conclusion: Qc-loaded TFs can be used as successful drug-delivery system for wound healing.


Download data is not yet available.


Theng MA, GR Sitaphale, KR Biyani. Evaluation of wound healing activity of polyherbal formulation. Int J Curr Pharm Res 2017;9:12-4.

Awad MA, A de Jager, LM van Westing. Flavonoid and chlorogenic acid levels in apple fruit: characterization of variation. Sci Horticulturae 2000;83:249-63.

Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000;63:1035-42.

Guardia T. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco 2001;56:683-7.

Vijayalakshmi A, G Madhira. Anti-psoriatic activity of flavonoids from Cassia tora leaves using the rat ultraviolet B ray photodermatitis model. Rev Brasileira Farmacognosia 2014;24:322-9.

Sim GS. Structure-activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast. Arch Pharm Res 2007;30:290-8.

Bors W. Flavonoids as antioxidants: determination of radical-scavenging efficiencies, in methods in enzymology, Academic Press; 1990. p. 343-55.

Saija A. Flavonoids as antioxidant agents: the importance of their interaction with biomembranes. Free Radical Biol Med 1995;19:481-6.

Priyanga KS, VK. Investigation of antioxidant potential of quercetin and hesperidin: an in vitro approach. Asian J Pharm Clin Res 2017;10:83-6.

Sivapriya V. Novel nanocarriers for ethnopharmacological formulations. Int J Appl Pharm 2018;10:26-30.

Olivella MS. Effects of dimethyl and menthol, permeation enhancers: evaluation by skin microdialysis in rats. J Pharm Pharmacol 2007;50:49-54.

Tan Q, Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. Int J Nanomed 2011;6:1621-30.

Kazi KM. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res 2010;1:374-80.

Jain S, A Diwan, S Sardana. Use of lactic acid and span 80 in the formulation of lipid-based imiquimod vesicles for genital warts. Int J Pharm Pharm Sci 2017;9:292-301.

Gizaway SE. Betamethasone dipropionate gel for the treatment of localized plaque psoriasis. Int J Pharm Pharm Sci 2017;9:173-82.

Cevc G, A Schatzlein, H Richardsen. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double-label CLSM experiments and direct size measurements. Biochim Biophysica Acta 2002;1564:21-30.

Elsayed MM. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm 2007;332:1-16.

Myers RH, DC Montgomery. Response surface methodology: product and process optimization using designed experiments. 2nd Edition ed. John Wiley and Sons, New York; 2002.

Rogerson A. The distribution of doxorubicin in mice following administration in niosomes. J Pharm Pharmacol 1988;40:337-42.

Ichino T. Antitumor effect of liposome-entrapped adriamycin administered via the portal vein. Japan J Cancer Res 1990;81:1052-6.

Wang J. Nanoscale amphiphilic macromolecules as lipoprotein inhibitors: the role of charge and architecture. Int J Nanomed 2007;2:697-705.

Jain S. Proultraflexible lipid vesicles for effective transdermal delivery of levonorgestrel: development, characterization, and performance evaluation. AAPS PharmSciTech 2005;6:E513-22.

AOAC. Official method of Analysis. 20th Edition. Association of Officiating Analytical Chemists. Washington DC, Method; 2016. p. 935.14, 992.24.

Shen LN. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. Int J Pharm 2014;460:280-8.

Begas E. Simple and reliable HPLC method for the monitoring of methotrexate in osteosarcoma patients. J Chromatogr Sci 2014;52:590-5.

Sendecor GW, WE. Cocharn statistical methods. 7th. Press: Ames Aiwa, Aiwa Sate Univ; 1980. p. 507.

Primarizky H, Yuniarti WM, Lukiswanto BS. Ellagic acid activity in healing process of the incision wound on male albino rats (Rattus norvegicus). KnE Life Sci 2017;3:224-33.

Beutler E, O Duron, BM Kelly. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.

Satoh K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978;90:37-43.

Ohkawa H, N Ohishi, K Yagi. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.

Montgomery HAC, Dymock JF. Colorimetric determination of nitrite. Analyst 1961;86:414.

Gornall AG, CJ Bardawill, MM David. Determination of serum proteins by means of the biuret reaction. J Biol Chem 1949;177:751-66.

Koracevic D. Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 2001;54:356-61.

Bancroft OD, A Stevens. Theory and practice of histological technique. Chirchil Livingstone, Edinburgh. London and New york; 2010.

Batavia R. The measurement of beclomethasone dipropionate entrapment in liposomes: a comparison of a microscope and an HPLC method. Int J Pharm 2001;212:109-19.

Verma DD. Particle size of liposomes influences the dermal delivery of substances into skin. Int J Pharm 2003;258:141-51.

Plessis D. The influence of particle size of liposomes on the disposition of drug into the skin. Int J Pharm 1994;103:277-82.

Das S, WK Ng, RB Tan. Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs? Eur J Pharm Sci 2012;47:139-51.

Cevc G. Transdermal drug delivery of insulin with ultradeformable carriers. Clin Pharmacokinet 2003;42:461-74.

Zeisig R, Shimada K, Hirota S, Arndt D. Effect of sterical stabilization on macrophage uptake in vitro and on thickness of the fixed aqueous layer of liposomes made from alkylphosphocholines. Biochim Biophys Acta 1285;1996:237–45.

Muller RH, C Jacobs, O Kayser. Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv Drug Delivery Rev 2001;47:3-19.

Abd-Elal RMA. Trans-nasal zolmitriptan novasomes: in vitro preparation, optimization and in vivo evaluation of brain targeting efficiency. Drug Delivery 2016;23:3374-86.

Abu El-Enin ASM. Proniosomal gel-mediated topical delivery of fluconazole: Development, in vitro characterization, and micro-biological evaluation. J Adv Pharm Technol Res 2019;10:20-6.

Chain E, I Kemp. The isoelectric points of lecithin and sphingomyelin. Biochem J 1934;28:2052-5.

Pichot R, RL Watson, IT Norton. Phospholipids at the interface: current trends and challenges. Int J Mol Sci 2013;14:11767-94.

Lim WM. Formulation and delivery of itraconazole to the brain using a nanolipid carrier system. Int J Nanomed 2014;9:2117-26.

Anwer MK. Development and evaluation of PLGA polymer-based nanoparticles of quercetin. Int J Biol Macromol 2016;92:213-9.

Pannerselvam AKS AR. Isolation, characterization and formulation properties of new plant gum obtained from mangifera indica. Int J Pharm Biomed Res 2010;1:35.

SF Ibrahim ESE, Aa KES. Thermal analysis and characterization of some cellulosic fabrics dyed by a new natural dye and mordanted with different mordants. Int J Chem 2011;3:40.

Zafeiri I. The role of surface-active species in the fabrication and functionality of edible solid lipid particles. J Colloid Interface Sci 2017;500:228-40.

Avadhani KS. Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation-induced skin damage. Drug Delivery 2017;24:61-74.

Sri KV. Preparation and characterization of quercetin and rutin cyclodextrin inclusion complexes. Drug Dev Ind Pharm 2007;33:245-53.

Basha MAEA S, Shamma R, Awad GJ. Design and optimization of surfactant-based nanovesicles for ocular delivery of clotrimazole. Liposome Res 2013;23:203–10.

Nasr AG A, Ghorab M. Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics 2016;8:20.

Rajan R. Transferosomes-a vesicular transdermal delivery system for enhanced drug permeation. J Adv Pharm Technol Res 2011;2:138-43.

Rai S, V Pandey, G Rai. Transfersomes as versatile and flexible nano-vesicular carriers in skin cancer therapy: the state of the art. Nano Rev Exp 2017;8:1325708.

Song HS. The effect of caffeic acid on wound healing in skin-incised mice. Korean J Physiol Pharmacol 2008;12:343-7.

Musalmah M. Comparative effects of palm vitamin E and alpha-tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats. Lipids 2005;40:575-80.

Sinno H. The effects of topical collagen treatment on wound breaking strength and scar cosmesis in rats. Canadian J Plastic Surgery 2012;20:181-5.

Weindl G. Hyaluronic acid in the treatment and prevention of skin diseases: molecular biological, pharmaceutical and clinical aspects. Skin Pharmacol Physiol 2004;17:207-13.

Boots AW. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 2008;24:703-10.

Schafer M, S Werner. Oxidative stress in normal and impaired wound repair. Pharmacol Res 2008;58:165-71.

Huxtable RJ. Physiological actions of taurine. Physiol Rev 1992;72:101-63.

Dincer S. Effect of taurine on wound healing. Amino Acids 1996;10:59-71.

Henderson WR, M Kaliner. Immunologic and nonimmunologic generation of superoxide from mast cells and basophils. J Clin Investigation 1978;61:187-96.

Fu J. Quercetin promotes diabetic wound healing via switching macrophages from M1 to M2 polarization. J Surgical Res 2020;246:213-23.



How to Cite




Original Article(s)