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Nanogels as controlled drug release systems for Coenzyme Q10 and Resveratrol for cosmetic application

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Abstract

Polymeric nanogels have been widely used as drug carrier systems due to their high drug loading capacity and an improved solubility of hydrophobic drugs. Many studies have shown that hydrophobic antioxidants, such as CoQ10 or Resveratrol, might improve healthy skin and be an effective anti-aging treatment by repairing photo-damaged skin. This study was carried out to develop a delivery system based on bio-compatible and water-dispersible nanogels capable of encapsulating Coenzyme Q10 (CoQ10) and Resveratrol. The nanogels are based on Pluronic® P123 coated with polyvinylpyrrolidone plus polyethyleneglycol (P123/PVP-PEG). Their physicochemical properties and morphological characteristics were evaluated in detail, as well as in vitro drug release. These nanogels were able to encapsulate and release Resveratrol and CoQ10 better than pure drugs at skin temperature (32 °C), from 31 to 43 and from 25 to 40%, respectively. The systems exhibited nanometric dimensions and spherical shape shown in the SEM and HRTEM micrographs. The bacterial bioassays studies showed that loaded materials do not affect bacterial growth. In addition, aqueous polymeric dispersions were stable for at least 24 h. The results indicated that the prepared nanogels were water-dispersible, non-toxic in the first tests, and they could be potential candidates for hydrophobic antioxidant release.

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References

  • Aslam SN, Stevenson PC, Kokubun T, Hall DR (2009) Antibacterial and antifungal activity of cicerfuran and related 2-arylbenzofurans and stilbenes. Microbiol Res 164:191–195

    Article  CAS  Google Scholar 

  • Alvarez SJ, Licea A, Cornejo JM, Frank CW (2011) Star polymers with random number of temperature sensitive arms and crosslinked poly(EGDMA)–core and their application to drug delivery. React Funct Polym 71:1077–1088

    Article  Google Scholar 

  • Arroyo E, Luque PA, Cosio M, Soto C, Villarreal R (2017) Study of a controlled release polymeric system based on Pluronic P123: spectroscopic characterization and theoretical model approach. J Mol Struct 1138:172–176

    Article  CAS  Google Scholar 

  • Burrell H (1957) Solubility Parameters of Resins off Dig 394:1069–1076

    Google Scholar 

  • Bae YH, Okano T, Hsu R, Kim SW (1987) Thermo-sensitive polymers as on-off switches for drug release. Die Makromolekulare Chemie Rapid Commun 8:481–485

    Article  CAS  Google Scholar 

  • Baker RW (1987) Controlled release of biologically active agents. Wiley

  • Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM (2000) Resveratrol acts as a mixed agonist/ antagonist for estrogen receptors alpha and beta. Endocrinology 141:3657–3667

    Article  CAS  Google Scholar 

  • Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506

    Article  CAS  Google Scholar 

  • Beg S, Javed S, JKohli K, (2010) Bioavailability enhancement of coenzyme Q10: an extensive review of patents. Recent Pat Drug Deliv Formul 4:245–257

    Article  CAS  Google Scholar 

  • Caracciolo PC, Pita CS, Abraham GA, Méndez JA, Molera J (2013) Synthesis, characterization and applications of amphiphilic elastomeric polyurethane networks in drug delivery. Polym J 45:331

    Article  CAS  Google Scholar 

  • Caddeo C, Pucci L, Gabriele M, Carbone C, Fernàndez-Busquets X, Valenti D, Manconi M (2018) Stability, biocompatibility and antioxidant activity of PEG-modified liposomes containing resveratrol. Int J Pharm 538:40–47

    Article  CAS  Google Scholar 

  • DesNoyer JR, McHugh AJ (2003) The effect of Pluronic on the protein release kinetics of an injectable drug delivery system. J Control Release 86:15–24

    Article  CAS  Google Scholar 

  • Danquah M, Fujiwara T, Mahato RI (2010) Self-assembling methoxypoly (ethylene glycol)-b-poly (carbonate-co-L-lactide) block copolymers for drug delivery. Biomaterials 31:2358–2370

    Article  CAS  Google Scholar 

  • Detoni CB, Souto GD, da Silva M, AL, Pohlmann AR, Guterres SS, (2012) Photostability and skin penetration of differente-resveratrol-loaded supramolecular structures. Photochem Photobiol 88:913–921

    Article  CAS  Google Scholar 

  • Duan Y, Cai X, Du H, Zhai G (2015) Novel in situ gel systems based on P123/TPGS mixed micelles and gellan gum for ophthalmic delivery of curcumin. Colloids Surf B 128:322–330

    Article  CAS  Google Scholar 

  • Feldstein MM, Shandryuk GA, Kuptsov SA, Platé NA (2000) Coherence of thermal transitions in poly (N-vinyl pyrrolidone)–poly (ethylene glycol) compatible blends 1. Interrelations among the temperatures of melting, maximum cold crystallization rate and glass transition. Polymer 41:5327–5338

    Article  CAS  Google Scholar 

  • Farage M, Miller K, Elsner P, Maibach H (2008) Intrinsic and extrinsic factors in skin ageing: A review. Int J Cosmet Sci 30:87–95

    Article  CAS  Google Scholar 

  • Farris P, Yatskayer M, Chen N, Krol Y, Oresajo C (2014) Evaluation of efficacy and tolerance of a nighttime topical antioxidant containing resveratrol, baicalin, and vitamine for treatment of mild to moderately photodamaged skin. J Drugs Dermatol 13:1467–1472

    CAS  Google Scholar 

  • Ferreira S, Silva F, Queiroz JA, Oleastro M, Domingues FC (2014) Resveratrol against Arcobacter butzleri and Arcobacter cryaerophilus: activity and effect on cellular functions. Int J Food Microbiol 180:62–68

    Article  CAS  Google Scholar 

  • Gehm BD, McAndrews JM, Chien PY, Jameson JL (1997) Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci USA 94:14138–14143

    Article  CAS  Google Scholar 

  • Gong C, Wang Y, Wang X, Wei X, Wu Q, Wang B, Qian Z (2011) Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic drug delivery, part 2: in vitro and in vivo toxicity evaluation. J Nanopart Res 13:721–731

    Article  CAS  Google Scholar 

  • Gupta RC (2012) Veterinary toxicology: basic and clinical principles. Elsevier Science. Academic press in press

  • Hung CF, Lin YK, Huang ZR, Fang JY (2008) Delivery of resveratrol, a red wine polyphenol, from solutions and hydrogels via the skin. Biol Pharm Bull 31:955–962

    Article  CAS  Google Scholar 

  • Ishii N, Senoo-Matsuda N, Miyake K, Yasuda K, Ishii T, Hartman PS, Furukawa S (2004) Coenzyme Q10 can prolong C. elegans lifespan by lowering oxidative stress. Mech Ageing Dev 125:41–46

    Article  CAS  Google Scholar 

  • Jun HW, West JL (2005) Modification of polyurethaneurea with PEG and YIGSR peptide to enhance endothelialization without platelet adhesion. J Biomed Mater Res 72B:131–139

    Article  CAS  Google Scholar 

  • Joubert LM (2009) Visualization of hydrogels with variable–pressure SEM. Microsc Microanal 15:1308–1309

    Article  Google Scholar 

  • Jing J, Alaimo D, De Vlieghere E, Jérôme C, De Wever O (2013) Tunable self–assembled nanogels composed of well–defined thermoresponsive hyaluronic acid–polymer conjugates. J Mater Chem B 1:3883–3887

    Article  CAS  Google Scholar 

  • Krutmann J, Schroeder P (2009) Role of mitochondria in photoaging of human skin: the defective powerhouse model. J Investig Dermatol Symp Proc 14:44–49

    Article  CAS  Google Scholar 

  • Kumpugdee-Vollrath M, Ibold Y (2012) Increasing solubility of poorly water soluble drug resveratrol by surfactants and cyclodextrins. Adv Mater Res 418:2231–2234

    Google Scholar 

  • Kim KM, Kim HM, Lee WJ, Lee CW (2014) Surface treatment of silica nanoparticles for stable and charge–controlled colloidal silica. Int J Nanomed 9:29–40

    Google Scholar 

  • Kyulavska M, Bryaskova R, Bozukova D, Mateva R (2014) Synthesis, structure and behavior of new polycaprolactam copolymers based on poly (ethylene oxide)–poly (propylene oxide)–poly (ethylene oxide) macroactivators derived from Pluronic block copolymers. J Polym Res 21:471

    Article  Google Scholar 

  • Lange R, Hengge-Aronis R (1991) Growth phase-regulated expression of bolA and morphology of stationary-phase Escherichia coli cells are controlled by the novel sigma factor sigma S. J Bacteriol 173:4474–4481

    Article  CAS  Google Scholar 

  • Littarru GP, Tiano L (2007) Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol 37:31–37

    Article  CAS  Google Scholar 

  • Li P, Dai YN, Zhang JP, Wang AQ, Wei Q (2008) Chitosan-alginate nanoparticles as a novel drug delivery system for nifedipine. Int J Biomed Sci 4:221–228

    CAS  Google Scholar 

  • Liu CB, Gong CY, Huang MJ, Wang JW, Pan YF, Zhang YD, Wei YQ (2008) Thermoreversible gel–sol behavior of biodegradable PCL-PEG-PCL triblock copolymer in aqueous solutions. J Biomed Mater Res 84B:165–175

    Article  CAS  Google Scholar 

  • Lorencini M, Brohem C, Dieamant G, Zanchin N, Maibach H (2014) Active ingredients against human epidermal aging. Ageing Res Rev 15:100–115

    Article  CAS  Google Scholar 

  • Lohan S, Bauersachs S, Ahlberg S, Baisaeng N, Keck C, Muller R, Witte E (2015) Ultra–small lipid nanoparticles promote the penetration of coenzyme Q10 in skin cells and counteract oxidative stress. Eur J Pharm Biopharm 89:201–207

    Article  CAS  Google Scholar 

  • Moreira T, Gutiérrez A, Delgado H (1994) Aspectos fisicosrelacionados con losaditivos en el proceso de liofilizacion. Papel Relevante De Loscarbohidratos Biotecnol Apl 11:113–119

    CAS  Google Scholar 

  • Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP (2002) Metabolism and disposition of resveratrol in rats: an extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model. J Pharmacol Exp Ther 302:369–373

    Article  CAS  Google Scholar 

  • Milne R, Block M (2004) Poly-MVA: A new supplement in the fight against cancer. Basic Health Publications North Bergen USA 1:45–46

    Google Scholar 

  • Marimuthu M, Bennet D, Kim S (2013) Self–assembled nanoparticles of PLGA–conjugated glucosamine as a sustained transdermal drug delivery vehicle. Polym J 45:202–209

    Article  CAS  Google Scholar 

  • Miller T, van Colen G, Sander B, Golas MM, Uezguen S, Weigandt M, Goepferich A (2013) Drug loading of polymeric micelles. Pharm Res 30:584–595

    Article  CAS  Google Scholar 

  • Mishra D, Hubenak JR, Mathur AB (2013) Nanoparticle systems as tools to improve drug delivery and therapeutic efficacy. J Biomed Mater Res 101A:3646–3660

    Article  CAS  Google Scholar 

  • Müller WA, Hassel M, Grealy M (2015) Growth control and cancer, in development and reproduction in humans and animal model species. Springer Berlin Heidelberg: Berlin, Heidelberg

  • Nair B (1998) Final report on the safety assessment of polyvinylpyrrolidone (PVP). Int J Toxicol 17:95–130

    Article  CAS  Google Scholar 

  • Nichols JA, Katiyar SK (2010) Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302:71–83

    Article  CAS  Google Scholar 

  • Niklowitz P, Menke T, Andler W, Okun JG (2004) Simultaneous analysis of coenzyme Q10 in plasma, erythrocytes, and platelets: comparison of the antioxidant level in blood cells and their environment in healthy children and after oral supplementation in adults. Clin Chim Acta 342:219–226

    Article  CAS  Google Scholar 

  • Ondarroa M, Sharma SK, Quinn PJ (1986) Solvation properties of ubiquinone-10 in solvents of different polarity. Biosci Rep 6:783–796

    Article  CAS  Google Scholar 

  • Oh JK, Lee DI, Park JM (2009) Biopolymer–based microgels/nanogels for drug delivery applications. Prog Polym Sci 34:1261–1282

    Article  CAS  Google Scholar 

  • Oliveira CP, Ribeiro MEN, Ricardo NM, Souza TVDP, Moura CL, Chaibundit C, Attwood D (2011) The effect of water-soluble polymers, PEG and PVP, on the solubilisation of griseofulvin in aqueous micellar solutions of Pluronic F127. Int J Pharm 421:252–257

    Article  CAS  Google Scholar 

  • Pourjavadi A, Dastanpour L, Tehrani ZM (2018) Magnetic micellar nanocarrier based on pH-sensitive PEG-PCL-PEG triblock copolymer: a potential carrier for hydrophobic anticancer drugs. J Nanopart Res 20:282

    Article  Google Scholar 

  • Roseman TJ, Higuchi WI (1970) Release of medroxyprogesterone acetate from a silicone polymer. J Pharm Sci 59:353–357

    Article  CAS  Google Scholar 

  • Richard M, Baxter A (2008) Anti–aging properties of resveratrol: review and report of a potent new antioxidant skin care formulation. J Cosmet Dermatol 7:2–7

    Article  Google Scholar 

  • Raemdonck K, Demeester J, De Smedt S (2009) Advanced nanogel engineering for drug delivery. Soft Matter 5:707–715

    Article  CAS  Google Scholar 

  • Rinnerthaler M, Bischof J, Streubel MK, Trost A, Richter K (2015) Oxidative stress in aging human skin. Biomol 5:545–589

    CAS  Google Scholar 

  • Shults CW, Haas RH, Passov D, Beal MF (1997) Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol 42:261–264

    Article  CAS  Google Scholar 

  • Schwarz J, Baisaeng N, Hoppel M, Low M, Keck C, Valenta C (2013) Ultra–small NLC for improved dermal delivery of coenzyme Q10. Int J Pharm 447:213–217

    Article  CAS  Google Scholar 

  • Sasaki Y, Akiyoshi K (2010) Nanogel engineering for new nanobiomaterials: from chaperoning engineering to biomedical applications. Chem Rec 10:366–376

    CAS  Google Scholar 

  • Sahiner N, Godbey WT, McPherson GL, John VT (2006) Microgel, nanogel and hydrogel–hydrogel semi–IPN composites for biomedical applications: synthesis and characterization. Colloid Polym Sci 284:1121–1129

    Article  CAS  Google Scholar 

  • Sezonov G, Joseleau-Petit D, D’Ari R (2007) Escherichia coli physiology in Luria-Bertani broth. J Bacteriol 189:8746–8749

  • Sharma A, Soliman GM, Al-Hajaj N, Sharma R, Maysinger D, Kakkar A (2011) Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria. Biomacromol 13:239–252

    Article  Google Scholar 

  • Senthilkumar M, Sheelarani B, Joshi RG, Dash S (2019) Solubilization and interaction of ciprofloxacin with pluronics and their mixed micelles. New J Chem 43:16530–16537

    Article  CAS  Google Scholar 

  • Tosato MG, Girón GVM, Martin AA, Tippavajhala VK, de Mele MFL, Dicelio L (2018) Comparative study of transdermal drug delivery systems of resveratrol: High efficiency of deformable liposomes. Mater Sci Eng C 90:356–364

    Article  CAS  Google Scholar 

  • Uhm YR, Rhee CK, Park JJ, Jun SH (2013) Morphologies and dispersion stabilities of carbon–encapsulated metal (Ag and Cu) nanoparticles synthesized by pulsed–wire evaporation (PWE). Res Chem Intermed 39:3387–3398

    Article  CAS  Google Scholar 

  • Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug Discov Today 10:1451–1458

    Article  CAS  Google Scholar 

  • Vermeij W, Alia A, Backendorf C (2011) ROS quenching potential of the epidermal cornified cell envelope. J Investig Dermatol 131:1435–1441

    Article  CAS  Google Scholar 

  • Wanka G, Hoffmann H, Ulbricht W (1994) Phase diagrams and aggregation behavior of poly (oxyethylene)-poly(oxypropylene)-poly(oxyethylene) triblock copolymers in aqueous solutions. Macromolecules 27:4145–4159

    Article  CAS  Google Scholar 

  • Weng T, Qi J, Lu Y, Wang K, Tian Z, Hu K, Wu W (2014) The role of lipid–based nano delivery systems on oral bioavailability enhancement of fenofibrate, a BCS II drug: comparison with fast–release formulations. J Nanobiotechnol 12:39–47

    Article  Google Scholar 

  • Washington KE, Kularatne RN, Biewer MC, Stefan MC (2018) Combination loading of doxorubicin and resveratrol in polymeric micelles for increased loading efficiency and efficacy. ACS Biomater Sci Eng 4:997–1004

    Article  CAS  Google Scholar 

  • Yan J, Ye Z, Chen M, Liu Z, Xiao Y, Zhang Y, Zhou Y, Tan W, Lang M (2011) Fine tuning micellar core-forming block of poly (ethylene glycol)-block-poly (ε-caprolactone) amphiphilic copolymers based on chemical modification for the solubilization and delivery of doxorubicin. Biomacromol 12:2562–2572

    Article  CAS  Google Scholar 

  • Yang X, Wu S, Xie W, Cheng A, Yang L, Hou Z, Jin X (2017) Dual–drug loaded nanoneedles with targeting property for efficient cancer therapy. J Nanobiotechnol 15:91–102

    Article  Google Scholar 

  • Zhao X, Hilliard LR, Mechery SJ, Wang Y, Bagwe RP, Jin S, Tan W (2004) A rapid bioassay for single bacterial cell quantitation using bioconjugated nanoparticles. Proc Natl Acad Sci USA 101:15027–15032

    Article  CAS  Google Scholar 

  • Zhang LW, Al–Suwayeh SA, Hsieh PW, Fang JY, (2010) A comparison of skin delivery of ferulic acid and its derivatives: evaluation of their efficacy and safety. Int J Pharm 399:44–51

    Article  CAS  Google Scholar 

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Acknowledgements

We extend our gratitude to F. Ruiz and E. Flores for their technical assistance.

Funding

E. Arroyo thanks CONACyT for her scholarship. The financial support was granted by CONACyT 174492.

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Correspondence to A. Olivas.

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Arroyo, E., Valdez, R., Cornejo-Bravo, J.M. et al. Nanogels as controlled drug release systems for Coenzyme Q10 and Resveratrol for cosmetic application. J Nanopart Res 23, 163 (2021). https://doi.org/10.1007/s11051-021-05243-z

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