Planta Med 2022; 88(06): 479-488
DOI: 10.1055/a-1464-1525
Formulation and Delivery Systems of Natural Products
Original Papers

Enhanced Skin Permeation of Punicalagin after Topical Application of Pluronic Micelles or Vesicles Loaded with Lafoensia pacari Extract

Sandra Alves de Sousa Garcia
1   Natural Products Research Laboratory (LPPN), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
Priscila Bianca Rodrigues da Rocha
2   Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
Bruno dos Santos Souza
2   Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
Andressa Tuane Santana Paz
1   Natural Products Research Laboratory (LPPN), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
Ana Luiza Caetano Negris
2   Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
Ricardo Neves Marreto
2   Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
Edemilson Cardoso da Conceição
1   Natural Products Research Laboratory (LPPN), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
1   Natural Products Research Laboratory (LPPN), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
,
2   Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy – Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil
› Author Affiliations
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico
Supported by: Fundação de Amparo à Pesquisa do Estado de Goiás
Supported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Abstract

Punicalagin, the principal ellagitannin of Lafoensia pacari leaves, has proven antioxidant activity, and standardized extracts of L. pacari can be topically used for skin aging management. We hypothesized that Pluronic nanomicelles or vesicles could solubilize sufficiently large amounts of the standardized extracts of L. pacari and provide chemical stability to punicalagin. The standardized extracts of L. pacari were obtained with an optimized extraction procedure, and the antioxidant activity was characterized. Formulations containing Pluronic at 25% and 35% were obtained with or without Span 80. They were characterized by average diameter, polydispersity index, punicalagin content, physicochemical stability, and rheology. A release and skin permeation study was carried out in vertical diffusion cells. The extraction procedure allowed quantifying high punicalagin content (i.e., 141.61 ± 3.87 mg/g). The standardized extracts of L. pacari showed antioxidant activity for all evaluated methods. Pluronic at 25 and Pluronic at 35 with standardized extracts of L. pacari showed an average diameter of about 25 nm. The addition of Span 80 significantly increased the mean diameter by 15-fold (p < 0.05), indicating the spontaneous formation of vesicles. Pluronic formulations significantly protected punicalagin from chemical degradation (p < 0.05). Pluronic at 25 formulations presented as free-flowing liquid-like systems, while Pluronic at 35 resulted in an increase of about 44-fold in |ƞ*|. The addition of Span 80 significantly reduced the Pluronic sol-gel transition temperature (p < 0.05), indicating the formation of vesicles. Formulations with Span 80 significantly enhanced punicalagin skin permeation compared to formulations without Span 80 (p < 0.05). Formulations with Span 80 were demonstrated to be the most promising formulations, as they allowed significant permeation of punicalagin (about 80 to 315 µg/cm2), which has been shown to have antioxidant activity.

Supporting Information



Publication History

Received: 23 October 2020

Accepted after revision: 22 March 2021

Article published online:
16 April 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Farage MA, Miller KW, Elsner P. Intrinsic and extrinsic factors in skin aging: a review. Int J Cosmet Sci 2008; 30: 87-95
  • 2 Chen X, Guo C, Kong J. Oxidative stress in neurodegenerative diseases. Neural Regen Res 2012; 7: 376-385
  • 3 Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The role of reactive oxygen species in the pathogenesis of Alzheimerʼs disease, Parkinsonʼs disease, and Huntingtonʼs disease: a mini review. Oxid Med Cell Longev 2016; 2016: 8590578
  • 4 Sampaio BL, Bara MTF, Ferri PH, Santos SDC, Paula JRD. Influence of environmental factors on the concentration of phenolic compounds in leaves of Lafoensia pacari . Rev Bras Farmacogn 2011; 21: 1127-1137
  • 5 Carneiro CC, da Costa Santos S, de Souza Lino jr. R, Bara MTF, Chaibub BA, de Melo Reis PR, Chen-Chen L. Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St.-Hil. Toxicol Appl Pharmacol 2016; 310: 1-8
  • 6 Pereira LOM, Vilegas W, Tangerina MMP, Arunachalam K, Balogun SO, Orlandi-Mattos PE, de Oliveira Martins DT. Lafoensia pacari A. St.-Hil.: wound healing activity and mechanism of action of standardized hydroethanolic leaves extract. J Ethnopharmacol 2018; 219: 337-350
  • 7 Aqil F, Munagala R, Vadhanam MV, Kausar H, Jeyabalan J, Schultz DJ, Gupta RC. Anti-proliferative activity and protection against oxidative DNA damage by punicalagin isolated from pomegranate husk. Food Res Int 2012; 49: 345-353
  • 8 Aloqbi A, Omar U, Yousr M, Grace M, Lila MA, Howell N. Antioxidant activity of pomegranate juice and Punicalagin. Nat Sci 2016; 8: 235-246
  • 9 Moilanen J, Karonen M, Tähtinen P, Jacquet R, Quideau S, Salminen JP. Biological activity of ellagitannins: effects as antioxidants, pro-oxidants and metal chelators. Phytochemistry 2016; 125: 65-72
  • 10 Xu L, He S, Yin P, Li D, Mei C, Yu X, Liu F. Punicalagin induces Nrf2 translocation and HO-1 expression via PI3K/Akt, protecting rat intestinal epithelial cells from oxidative stress. Int J Hyperth 2016; 32: 465-473
  • 11 Pouységu L, Deffieux D, Malik G, Natangelo A, Quideau S. Synthesis of ellagitannin natural products. Nat Prod Rep 2011; 28: 853-874
  • 12 Lu J, Ding K, Yuan Q. One-step purification of punicalagin by preparative HPLC and stability study on punicalagin. Sep Sci Technol 2010; 46: 147-154
  • 13 Sguizzato M, Valacchi G, Pecorelli A, Boldrini P, Simelière F, Huang N, Esposito E. Gallic acid loaded poloxamer gel as new adjuvant strategy for melanoma: a preliminary study. Colloids Surf B Biointerfaces 2020; 185: 110613
  • 14 Abd E, Yousef SA, Pastore MN, Telaprolu K, Mohammed YH, Namjoshi S, Roberts MS. Skin models for the testing of transdermal drugs. Clin Pharmacol 2016; 8: 163
  • 15 Taveira SF, Varela-Garcia A, Dos Santos Souza B, Marreto RN, Martin-Pastor M, Concheiro A, Alvarez-Lorenzo C. Cyclodextrin-based poly(pseudo)rotaxanes for transdermal delivery of carvedilol. Carbohydr Polym 2018; 200: 278-288
  • 16 Marreto RN, Cardoso G, Dos Santos Souza B, Martin-Pastor M, Cunha-Filho M, Taveira SF, Alvarez-Lorenzo C. Hot melt-extrusion improves the properties of cyclodextrin-based poly(pseudo)rotaxanes for transdermal formulation. Int J Pharm 2020; 586: 119510
  • 17 Fakhari A, Corcoran M, Schwarz A. Thermogelling properties of purified poloxamer 407. Heliyon 2017; 3: e00390
  • 18 Alvarez-Lorenzo C, Concheiro A. Polymeric micelles as drug stabilizers: the camptothecin and simvastatin cases. J Drug Deliv Sci Technol 2010; 20: 249-257
  • 19 Chen S, Yang B, Guo C, Ma JH, Yang LR, Liang X, Hua C, Liu HZ. Spontaneous vesicle formation of poly(ethylene oxide)-poly(propyleneoxide)-poly(ethylene oxide) triblock copolymer. J Phys Chem B 2008; 112: 15659-15665
  • 20 Gangulya R, Kunwar A, Dutta B, Kumar S, Barick KC, Ballal A, Aswal VK, Hassan PA. Heat-induced solubilization of curcumin in kinetically stable Pluronic P123 micelles and vesicles: an exploit of slow dynamics of the micellar restructuring processes in the aqueous Pluronic system. Colloids Surf B Biointerfaces 2017; 152: 176-182
  • 21 Sakai T, Kurosawa H, Okada T, Mishima S. Vesicle formation in mixture of a PEO-PPO-PEO block copolymer (Pluronic P123) and a nonionic surfactant (Span 65) in water. Colloids Surf A Physicochem Eng Asp 2011; 389: 82-89
  • 22 Bodratti AM, Alexandridis P. Formulation of poloxamers for drug delivery. J Funct Biomater 2018; 9: 11
  • 23 Li Y, Bi Y, Xi Y, Li L. Enhancement on oral absorption of paclitaxel by multifunctional Pluronic micelles. J Drug Target 2013; 21: 188-199
  • 24 Makhmalzade BS, Chavoshy F. Polymeric micelles as cutaneous drug delivery system in normal skin and dermatological disorders. J Adv Pharm Technol Res 2018; 9: 2-8
  • 25 Campos JS, Frasson APZ. Avaliação da atividade antioxidante do extrato aquoso de Lafoensia pacari A. ST-HIL em emulsão não-iônica. J Appl Pharm Sci 2011; 32: 363-368
  • 26 Baccarin T, Lemos-Senna E. Potential application of nanoemulsions for skin delivery of pomegranate peel polyphenols. AAPS PharmSciTech 2017; 18: 3307-3314
  • 27 BRASIL. Agência Nacional de Vigilância Sanitária. Guia de Estabilidade de Produtos Cosméticos 2004; 1: 52
  • 28 Venkataramanamma D, Aruna P, Singh RP. Standardization of the conditions for extraction of polyphenols from pomegranate peel. J Food Sci Technol 2016; 53: 2497-2503
  • 29 Lachenmeier DW. Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. J Occup Med Toxicol 2008; 3: 26
  • 30 Serafini LF, Schmidt CAP, Oldoni TLC, Carpes ST, Haminiuk CWI, Ribeiro IS. Assessment of antioxidant activity of ethanolic extracts of marjoram (Origanum majorana L.) evaluated by different in vitro methods. Acta Hortic 2018; 1198: 85-92
  • 31 Bartelds R, Nematollahi MH, Pols T, Stuart MCA, Pardakhty A, Asadikaram G, Poolman B. Niosomes, an alternative for liposomal delivery. PLoS One 2018; 13: e0194179
  • 32 Damera DP, Venuganti VVK, Nag A. Deciphering the role of bilayer of a niosome towards controlling the entrapment and release of dyes. Chemistry Select 2018; 3: 3930-3938
  • 33 Kato K, Walde P, Koine N, Ichikawa S, Ishikawa T, Nagahama R, Ishihara T, Tsujii T, Shudou M, Omokawa Y, Kuroiwa T. Temperature-sensitive nonionic vesicles prepared from span 80 (sorbitan monooleate). Langmuir 2008; 24: 10762-10770
  • 34 Yoshioka T, Sternberg B, Floresnce AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (span 20, 40, 60 and 80) and a sorbitan triester (span 85). Int J Pharm 1994; 105: 1-6
  • 35 Barradas TN, Lopes LMA, Ricci-Júnior E, Silva KGDH, Mansur CRE. Development and characterization of micellar systems for application as insect repellents. Int J Pharm 2013; 454: 633-640
  • 36 De Francisco LMB, Rosseto HC, de Toledo LDAS, dos Santos RS, de Souza Ferreira SB, Bruschi ML. Organogel composed of poloxamer 188 and passion fruit oil: sol-gel transition, rheology, and mechanical properties. J Mol Liq 2019; 289: 111170
  • 37 Fernández VVA, Tepale N, Alvarez JG, Pérez-López JH, Macı ER, Bautista F, Puig JE. Rheology of the Pluronic P103/water system in a semidilute regime: evidence of nonequilibrium critical behavior. J Colloid Interface Sci 2009; 336: 842-849
  • 38 Zhao XY, Xu J, Zheng LQ, Li XW. Preparation of temperature-sensitive microemulsion-based gels formed from a triblock copolymer. Colloids Surf A Physicochem Eng Asp 2007; 307: 100-107
  • 39 Šegota S, Težak D. Spontaneous formation of vesicles. Adv Colloid Interface Sci 2006; 121: 51-75
  • 40 Stuart MCA, Boekema EJ. Two distinct mechanisms of vesicle-to-micelle and micelle-to-vesicle transition are mediated by the packing parameter of phospholipid–detergent systems. Biochim Biophys Acta 2007; 1768: 2681-2689
  • 41 Molina PM, Gradzielski M. Gels obtained by colloidal self-assembly of amphiphilic molecules. Gels 2017; 3: 1-30
  • 42 Pereira GG, Dimer FA, Guterres SS, Kechinski CP, Granada JE, Cardozo NS. Formulation and characterization of poloxamer 407 thermoreversible gel containing polymeric microparticles and hyaluronic acid. Quim Nova 2013; 36: 1121-1125
  • 43 da Rocha PBR, dos Santos Souza B, Andrade LM, Marreto RN, Lima EM, Taveira SF. Development of a high-performance liquid chromatographic method for asiaticoside quantification in different skin layers after topical application of a Centella asiatica extract. Planta Med 2017; 83: 1431-1437
  • 44 Shin S, Cho C, Oh I. Effects of non-ionic surfactants as permeation enhancers towards piroxicam from the poloxamer gel through rat skins. Int J Pharm 2001; 222: 199-203
  • 45 Wang W, Liu C, Luo Z, Wan X, Fang L. Investigation of molecular mobility of pressure-sensitive-adhesive in oxybutynin patch in vitro and in vivo: effect of sorbitan monooleate on drug release and patch mechanical property. Eur J Pharm 2018; 122: 116-124
  • 46 FDA (Food and Drug Administration). Guidance for Industry: Q2B Validation of analytical Procedures. Rockville, USA: U. S. Department of Health and Human Services; 1996
  • 47 Rufino MSM, Alves RE, de Brito ES, de Morais SM, Sampaio CDG, Pérez-Jimenez J, Saura-Calixto FD. Metodologia científica: determinação da atividade antioxidante total em frutas pela captura do radical livre DPPH. Embrapa Agroindústria Tropical, Technical Note, 127. 2007 Accessed April 7, 2021 at: https://ainfo.cnptia.embrapa.br/digital/bitstream/CNPAT/10224/1/Cot_127.pdf
  • 48 Rufino MSM, Alves RE, De Brito ES, De Morais SM, Sampaio CDG, Pérez-Jiménez J, Saura-Calixto FD. Metodologia científica: determinação da atividade antioxidante total em frutas pela captura do radical livre ABTS. Embrapa Agroindústria Tropical, Technical Note, 128. 2007 Accessed April 7, 2021 at: https://ainfo.cnptia.embrapa.br/digital/bitstream/CNPAT/10225/1/Cot_128.pdf
  • 49 Rufino MSM, Alves RE, De Brito ES, De Morais SM, Sampaio CDG, Pérez-Jiménez J, Saura-Calixto FD. Metodologia científica: determinação da atividade antioxidante total em frutas pelo método de redução do ferro (FRAP). Embrapa Agroindústria Tropical, Technical Note, 125. 2006 Accessed April 7, 2021 at: https://ainfo.cnptia.embrapa.br/digital/bitstream/CNPAT-2010/11964/1/cot-125.pdf
  • 50 Esposito E, Carotta V, Scabbia A, Trombelli L, Dʼantona P, Menegatti E, Nastruzzi C. Comparative analysis of tetracycline-containing dental gels: poloxamer-and monoglyceride-based formulations. Int J Pharm 1996; 142: 9-23