Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein - PubMed (original) (raw)

Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein

Débora Fretes Argenta et al. Int J Nanomedicine. 2014.

Abstract

The aim of this study was to optimize topical nanoemulsions containing genistein, by means of a 23 full factorial design based on physicochemical properties and skin retention. The experimental arrangement was constructed using oil type (isopropyl myristate or castor oil), phospholipid type (distearoylphosphatidylcholine [DSPC] or dioleylphosphaditylcholine [DOPC]), and ionic cosurfactant type (oleic acid or oleylamine) as independent variables. The analysis of variance showed effect of third order for particle size, polydispersity index, and skin retention of genistein. Nanoemulsions composed of isopropyl myristate/DOPC/oleylamine showed the smallest diameter and highest genistein amount in porcine ear skin whereas the formulation composed of isopropyl myristate/DSPC/oleylamine exhibited the lowest polydispersity index. Thus, these two formulations were selected for further studies. The formulations presented positive ζ potential values (>25 mV) and genistein content close to 100% (at 1 mg/mL). The incorporation of genistein in nanoemulsions significantly increased the retention of this isoflavone in epidermis and dermis, especially when the formulation composed by isopropyl myristate/DOPC/oleylamine was used. These results were supported by confocal images. Such formulations exhibited antiherpetic activity in vitro against herpes simplex virus 1 (strain KOS) and herpes simplex virus 22 (strain 333). Taken together, the results show that the genistein-loaded nanoemulsions developed in this study are promising options in herpes treatment.

Keywords: antiherpetic activity; cationic nanoemulsions; phospholipids; skin retention.

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Figures

Figure 1

Figure 1

TEM images of the selected nanoemulsions composed of IM/DSPC/OLA (NE1) and IM/DOPC/OLA (NE3). No differences were detected in the morphology of oil droplets of NE1 and NE3. Note: Scale bar =200 nm. Abbreviations: DOPC, dioleylphosphaditylcholine; DSPC, distearoylphosphatidylcholine; IM, isopropyl myristate; NE, nanoemulsion; OLA, oleylamine; TEM, transmission electron microscope.

Figure 2

Figure 2

Distribution profile of genistein into porcine ear skin layers after 8 hours of permeation/retention study, from a control solution (PG solution) and NE1 and NE3. Notes: A lower amount of genistein was detected in the stratum corneum from nanoemulsions, with a significantly increased retention of this isoflavone into epidermis and dermis. The values are means ± SD of five experiments. *Significantly lower (P<0.05) for PG in stratum corneum, epidermis and dermis as compared to NE1 and NE3; **significantly higher (P<0.05) for NE3 in epidermis and dermis as compared with PG and NE1. Abbreviations: PG, propylene glycol; NE, nanoemulsion; SD, standard deviation.

Figure 3

Figure 3

Hematoxylin-/eosin-stained histological (A–C) or fluorescent (D–F) images of full-thickness porcine ear skin treated with a genistein propylene glycol solution (A and D) or with genistein-loaded NE1 (B and E) or NE3 (C and F). Notes: Histological images show no skin damage after treatment with the nanoemulsions. The confocal images revealed that the dye Nile Red was mainly located in stratum corneum when dispersed in propylene glycol. However, the fluorescence was distributed throughout the skin layers when the dye was incorporated into nanoemulsions. Images were obtained after 8 hours of permeation/retention studies using a Franz diffusion cell. Images were obtained at ×10 magnification. Nile Red was used as fluorescent dye in confocal images. Abbreviation: NE, nanoemulsion.

Figure 4

Figure 4

Factorial plots of three-way interactions for droplet size response, polydispersity index response, and genistein retention in the skin. Notes: The graphical representation shows that the NE3 presented the lowest droplet size and the highest genistein retention in the porcine ear skin. The NE1 presented the lowest polydispersity index. The plots were obtained from measured responses. Abbreviations: DOPC, dioleylphosphaditylcholine; DSPC, distearoylphosphatidylcholine; NE, nanoemulsion; PI, polydispersity index.

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References

    1. Brady RC, Bernstein DI. Treatment of herpes simplex virus infections. Antiviral Res. 2004;61(2):73–81. - PubMed
    1. Simmons A. Clinical manifestations and treatment considerations of herpes simplex virus infection. J Infect Dis. 2002;186(Suppl 1):S71–S77. - PubMed
    1. Mundinger TA, Efferth T. Herpes simplex virus: Drug resistance and new treatment options using natural products (Review) Mol Med Rep. 2008;1(5):611–616. - PubMed
    1. Field HJ. Herpes simplex virus antiviral drug resistance – current trends and future prospects. J Clin Virol. 2001;21(3):261–269. - PubMed
    1. Chiang LC, Chiang W, Chang MY, Ng LT, Lin CC. Antiviral activity of Plantago major extracts and related compounds in vitro. Antiviral Res. 2002;55(1):53–62. - PubMed

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