A New Controlled Release System for Propolis Polyphenols and Its Biochemical Activity for Skin Applications

Propolis is a resinous substance produced by bees that exhibits antimicrobial, immunostimulatory and antioxidant activity. Its use is common in functional foods, cosmetics and traditional medicine despite the fact that it demonstrates low extraction yields and inconsistency in non-toxic solvents. In this work, a new encapsulation and delivery system consisting of liposomes and cyclodextrins incorporating propolis polyphenols has been developed and characterized. The antioxidant, antimutagenic and antiaging properties of the system under normal and UVB-induced oxidative stress conditions were investigated in cultured skin cells and/or reconstituted skin model. Furthermore, the transcript accumulation for an array of genes involved in many skin-related processes was studied. The system exhibits significant polyphenol encapsulation efficiency, physicochemical stability as well as controlled release rate in appropriate conditions. The delivery system can retain the anti-mutagenic, anti-oxidative and anti-ageing effects of propolis polyphenols to levels similar and comparable to those of propolis methanolic extracts, making the system ideal for applications where non-toxic solvents are required and controlled release of the polyphenol content is desired.

[1]  L. Gould,et al.  Protease-Resistant Growth Factor Formulations for the Healing of Chronic Wounds. , 2020, Advances in wound care.

[2]  A. Galanis,et al.  Honey Extracts Exhibit Cytoprotective Properties against UVB-Induced Photodamage in Human Experimental Skin Models , 2020, Antioxidants.

[3]  H. Harn,et al.  Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain , 2020, International journal of molecular sciences.

[4]  Ö. Özer,et al.  Propolis loaded liposomes: evaluation of antimicrobial and antioxidant activities , 2019, Journal of liposome research.

[5]  N. Frangogiannis,et al.  The role of Smad2 and Smad3 in regulating homeostatic functions of fibroblasts in vitro and in adult mice. , 2020, Biochimica et biophysica acta. Molecular cell research.

[6]  E. Franceschi,et al.  Encapsulation of Red Propolis in Polymer Nanoparticles for the Destruction of Pathogenic Biofilms , 2020, AAPS PharmSciTech.

[7]  C. Hepokur,et al.  Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells , 2020, Nutrition and cancer.

[8]  Wei Zhao,et al.  Preparation and Characterisation of Polyphenol-HP-β-Cyclodextrin Inclusion Complex that Protects Lamb Tripe Protein against Oxidation , 2019, Molecules.

[9]  I. Mourtzinos,et al.  A natural approach in food preservation: Propolis extract as sorbate alternative in non-carbonated beverage. , 2019, Food chemistry.

[10]  J. M. D. M. de Moura Bell,et al.  In vitro and in vivo antioxidant properties of bioactive compounds from green propolis obtained by ultrasound-assisted extraction , 2019, Food chemistry: X.

[11]  K. Münstedt,et al.  Using Bee Products for the Prevention and Treatment of Oral Mucositis Induced by Cancer Treatment , 2019, Molecules.

[12]  M. El-Naggar,et al.  Wound dressing properties of cationized cotton fabric treated with carrageenan/cyclodextrin hydrogel loaded with honey bee propolis extract. , 2019, International journal of biological macromolecules.

[13]  B. Lyoussi,et al.  Insight on Propolis from Mediterranean Countries: Chemical Composition, Biological Activities and Application Fields , 2019, Chemistry & biodiversity.

[14]  Z. Hosseinidoust,et al.  Liposomal Nanovesicles for Efficient Encapsulation of Staphylococcal Antibiotics , 2019, ACS omega.

[15]  Aglaia Pappa,et al.  Propolis Extracts Inhibit UV-Induced Photodamage in Human Experimental In Vitro Skin Models , 2019, Antioxidants.

[16]  A. Fontana,et al.  Effect of the Incorporation of Functionalized Cyclodextrins in the Liposomal Bilayer , 2019, Molecules.

[17]  Yujuan Xu,et al.  One-step assembly of zein/caseinate/alginate nanoparticles for encapsulation and improved bioaccessibility of propolis. , 2019, Food & function.

[18]  Hua Sun,et al.  Composition design and medical application of liposomes. , 2019, European journal of medicinal chemistry.

[19]  B. A. Machado,et al.  Chemical characterization and biological activity of six different extracts of propolis through conventional methods and supercritical extraction , 2018, PloS one.

[20]  Dina M El-Kersh,et al.  Propolis-based niosomes as oromuco-adhesive films: A randomized clinical trial of a therapeutic drug delivery platform for the treatment of oral recurrent aphthous ulcers , 2018, Scientific Reports.

[21]  Khalid Ali Khan,et al.  Composition and functional properties of propolis (bee glue): A review , 2018, Saudi journal of biological sciences.

[22]  G. R. Andrade,et al.  Development and characterization of microencapsules containing spray dried powder obtained from Brazilian brown, green and red propolis. , 2018, Food research international.

[23]  I. Junttila Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes , 2018, Front. Immunol..

[24]  Ling-Yong Xiao,et al.  Bee venom therapy: Potential mechanisms and therapeutic applications , 2018, Toxicon : official journal of the International Society on Toxinology.

[25]  Modestas Žilius,et al.  Comparison of aqueous, polyethylene glycol-aqueous and ethanolic propolis extracts: antioxidant and mitochondria modulating properties , 2018, BMC Complementary and Alternative Medicine.

[26]  J. Kocot,et al.  Antioxidant Potential of Propolis, Bee Pollen, and Royal Jelly: Possible Medical Application , 2018, Oxidative medicine and cellular longevity.

[27]  Yonghee Lee,et al.  Anti‑apoptotic effects of glycosaminoglycans via inhibition of ERK/AP‑1 signaling in TNF‑α‑stimulated human dermal fibroblasts. , 2018, International journal of molecular medicine.

[28]  P. Djurdjevic,et al.  Cytotoxic, proapoptotic and antioxidative potential of flavonoids isolated from propolis against colon (HCT-116) and breast (MDA-MB-231) cancer cell lines. , 2018, Food research international.

[29]  Navjot Shah,et al.  Anticancer Activity in Honeybee Propolis: Functional Insights to the Role of Caffeic Acid Phenethyl Ester and Its Complex With γ-Cyclodextrin , 2018, Integrative cancer therapies.

[30]  M. Bordonaro,et al.  Hypothesis: Induction of biomarkers for detection of colonic neoplasms , 2018, Journal of Cancer.

[31]  K. Mahadik,et al.  Standardization, anti-carcinogenic potential and biosafety of Indian propolis , 2017, Journal of Ayurveda and integrative medicine.

[32]  J. Lobaccaro,et al.  Biological properties of propolis extracts: Something new from an ancient product. , 2017, Chemistry and physics of lipids.

[33]  N. Labrou,et al.  Skin Protective Effects of Nannochloropsis gaditana Extract on H2O2-Stressed Human Dermal Fibroblasts , 2017, Front. Mar. Sci..

[34]  H. Kalofonos,et al.  Characterization and Biological Evaluation of Propolis from Poland , 2017, Molecules.

[35]  A. Nematollahi,et al.  Propolis Diterpenes as a Remarkable Bio-Source for Drug Discovery Development: A Review , 2017, International journal of molecular sciences.

[36]  G. Rimbach,et al.  Anti-Inflammatory Properties of Brazilian Green Propolis Encapsulated in a γ-Cyclodextrin Complex in Mice Fed a Western-Type Diet , 2017, International journal of molecular sciences.

[37]  M. P. Lambregtse-van den Berg,et al.  Interventions to treat mental disorders during pregnancy: A systematic review and multiple treatment meta-analysis , 2017, PloS one.

[38]  Abolfazl Akbarzadeh,et al.  Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications , 2017, Artificial cells, nanomedicine, and biotechnology.

[39]  I. Kosalec,et al.  The Influence of Extraction Parameters on Antimicrobial Activity of Propolis Extracts , 2017, Natural product communications.

[40]  B. Denisow,et al.  Biological and therapeutic properties of bee pollen: a review. , 2016, Journal of the science of food and agriculture.

[41]  S. Kaul,et al.  Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin , 2016, Journal of Cancer.

[42]  D. Watson,et al.  Polymeric Nanoparticles of Brazilian Red Propolis Extract: Preparation, Characterization, Antioxidant and Leishmanicidal Activity , 2016, Nanoscale Research Letters.

[43]  N. Saavedra,et al.  Polyphenols from Chilean Propolis and Pinocembrin Reduce MMP-9 Gene Expression and Activity in Activated Macrophages , 2016, BioMed research international.

[44]  P. Shetty,et al.  Quercetin Influences Quorum Sensing in Food Borne Bacteria: In-Vitro and In-Silico Evidence , 2015, PloS one.

[45]  T. Grune,et al.  Determination of protein carbonyls in plasma, cell extracts, tissue homogenates, isolated proteins: Focus on sample preparation and derivatization conditions , 2015, Redox biology.

[46]  A. Molinari,et al.  Liposomes as nanomedical devices , 2015, International journal of nanomedicine.

[47]  N. N. Pathak,et al.  Curcumin-induced angiogenesis hastens wound healing in diabetic rats. , 2015, The Journal of surgical research.

[48]  E. Fanizza,et al.  A new complex of curcumin with sulfobutylether-β-cyclodextrin: characterization studies and in vitro evaluation of cytotoxic and antioxidant activity on HepG-2 cells. , 2014, Journal of pharmaceutical sciences.

[49]  P. Carmeliet,et al.  The multifaceted activity of VEGF in angiogenesis - Implications for therapy responses. , 2014, Cytokine & growth factor reviews.

[50]  J. Quiles,et al.  Polyphenol-Rich Strawberry Extract Protects Human Dermal Fibroblasts against Hydrogen Peroxide Oxidative Damage and Improves Mitochondrial Functionality , 2014, Molecules.

[51]  C. Morgan,et al.  Naturally derived factors and their role in the promotion of angiogenesis for the healing of chronic wounds , 2013, Angiogenesis.

[52]  Hongyan Wang,et al.  Integrin signalling and function in immune cells , 2012, Immunology.

[53]  Costas Demetzos,et al.  Thermodynamic and structural characterization of Liposomal-Locked in-Dendrimers as drug carriers. , 2010, Colloids and surfaces. B, Biointerfaces.

[54]  T. Werfel,et al.  Innate immunity, allergy and atopic dermatitis , 2010, Current opinion in allergy and clinical immunology.

[55]  A. Verkman,et al.  Roles of aquaporin-3 in the epidermis. , 2008, The Journal of investigative dermatology.

[56]  I. Mourtzinos,et al.  Encapsulation of complex extracts in β-cyclodextrin: An application to propolis ethanolic extract , 2008, Journal of microencapsulation.

[57]  Z. Bi,et al.  EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration. , 2006, The Biochemical journal.

[58]  H. Hepburn,et al.  Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models. , 2005, Journal of ethnopharmacology.

[59]  A. Hensel,et al.  Kiwi fruit (Actinidia chinensis L.) polysaccharides exert stimulating effects on cell proliferation via enhanced growth factor receptors, energy production, and collagen synthesis of human keratinocytes, fibroblasts, and skin equivalents , 2005, Journal of cellular physiology.

[60]  D. Graves,et al.  TNF‐α in vivo stimulates apoptosis in fibroblasts through caspase‐8 activation and modulates the expression of pro‐apoptotic genes , 2004, Journal of cellular physiology.

[61]  S. Werner,et al.  Regulation of wound healing by growth factors and cytokines. , 2003, Physiological reviews.

[62]  A. Moorman,et al.  Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data , 2003, Neuroscience Letters.

[63]  Roberto Colombo,et al.  Protein carbonyl groups as biomarkers of oxidative stress. , 2003, Clinica chimica acta; international journal of clinical chemistry.

[64]  P. Kefalas,et al.  Correlation of Pigment and Flavanol Content with Antioxidant Properties in Selected Aged Regional Wines from Greece , 2002 .

[65]  L. Maďarová [Antibacterial properties of propolis]. , 1980, Ceskoslovenska stomatologie.

[66]  C. Berset,et al.  Use of a Free Radical Method to Evaluate Antioxidant Activity , 1995 .

[67]  R. Kozłowski,et al.  The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity. , 1993, Journal of immunological methods.