Percutaneous absorption of benzophenone-3 loaded lipid nanoparticles and polymeric nanocapsules: A comparative study

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Abstract

For the last years, the increase of the number of skin cancer cases led to a growing awareness of the need of skin protection against ultraviolet (UV) radiations. Chemical UV filters are widely used into sunscreen formulations as benzophenone-3 (BP-3), a usually used broad spectrum chemical UV filter that has been shown to exercise undesirable effects after topical application. Innovative sunscreen formulations are thus necessary to provide more safety to users. Lipid carriers seem to be a good alternative to formulate chemical UV filters reducing their skin penetration while maintaining good photo-protective abilities. The aim of this work was to compare percutaneous absorption and cutaneous bioavailability of BP-3 loaded into solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanostructured polymeric lipid carriers (NPLC) and nanocapsules (NC). Particle size, zeta potential and in vitro sun protection factor (SPF) of nanoparticle suspensions were also investigated. Results showed that polymeric lipid carriers, comprising NPLC and NC, significantly reduced BP-3 skin permeation while exhibiting the highest SPF. This study confirms the interesting potential of NPLC and NC to formulate chemical UV filters.

Introduction

Ultraviolet (UV) radiations have been correlated with the increasing incidence of skin carcinomas and melanomas (Armstrong and Kricker, 2001). Sunscreen use is a widespread practice protecting the skin against damages due to sun UV radiation over exposure. Sunscreen formulations contain physical and/or chemical UV filters able to scatter and/or to absorb UVB and UVA radiations respectively. Chemical UV filters are preferentially incorporated into sunscreen preparations since they are easily formulated and do not leave unpleasant white marks at skin surface as compared to physical UV filters (Anderson et al., 1997, Krause et al., 2012, Gilbert et al., 2013). To be efficient, UV filters must remain at the uppermost skin regions (Lu et al., 1999). Although the stratum corneum (SC) is considered to be an efficient barrier to exogenous agents, UV radiations can weaken this barrier function enhancing chemical skin penetration (Yamamoto et al., 2008). Some studies revealed that several chemical UV filters, like benzophenone-3 (BP-3), could permeate through the skin leading to undesirable effects (Krause et al., 2012, Gilbert et al., 2013). Indeed, physico-chemical properties of BP-3 (Table 1) make it a good candidate to penetrate SC which ensures skin barrier function. BP-3 has often been reported to be allergenic (Bryden et al., 2006), to act as an endocrine disruptor (Kim et al., 2014) and to be detected into blood plasma, human breast milk as well as urines which renders this molecule to be considered of high concern in relation to human risk (Kasichayanula et al., 2007, Schlumpf et al., 2008, Wong and Orton, 2011). Due to the favorable properties of BP-3 to penetrate the skin, the study of the effect of different formulation in infinite dose on the penetration properties of BP-3 could produce interesting data. Several studies focused on the interest of micro and nanocarriers to formulate chemical UV filters protecting them from photo-degradation and preventing their permeation across the skin (Jiménez et al., 2004, Mestres et al., 2010, Sanad et al., 2010, Lacatusu et al., 2011). Indeed, previous studies showed that BP-3 incorporation into solid lipid nanoparticles (SLN), in comparison with classical oil in water emulsion, reduced its percutaneous absorption by 50% (Wissing and Müller, 2002a, Puglia et al., 2014). Polymeric lipid nanocapsules were also previously shown to decrease BP-3 skin permeation while enhancing their photoprotection abilities (Marcato et al., 2011). The many studies published confirm the interest of formulating innovative UV filter carriers to achieve high skin photoprotection while reducing undesirable effects linked to their penetration into the skin. Lipid nanoparticles and nanocapsules are colloidal carriers which are extensively under investigations as drug carrier systems for poorly water-soluble compounds (Müller et al., 2002a, Dash and Konkimalla, 2012, Steelandt et al., 2014). These lipid carriers permit (i) to protect chemical compounds from photo-degradation phenomena, (ii) bioavailability improvement and (iii) controlled release while allowing large scale production (Jee et al., 2006, Puglia et al., 2012, Frank et al., 2015). These colloidal carriers have been demonstrated to enhance the accumulation of UV filters at the uppermost skin layers, where they are designed to act, and to enhance their photo-protection abilities (Müller et al., 2002b, Marcato et al., 2011, Puglia et al., 2012). Lipid nanocarrier size facilitates their formulation in dermatological products and enables comfortable skin application (Müller et al., 2002b). SLN are based on melt-emulsified lipids which are solid at room temperature and made of physiologically well tolerated and biodegradable raw materials (Wissing and Müller, 2001, Alvarez-Roman et al., 2001). Nanostructured lipid carriers (NLC) are characterized by a solid lipid matrix in which a liquid lipid is added (Chen et al., 2014). NLC are the second generation of SLN permitting (i) a more efficient drug loading, (ii) a modulation of the drug delivery profile and (iii) a prolonged drug entrapment during storage (Das et al., 2012). Nanostructured polymeric lipid carriers (NPLC) and nanocapsules (NC) are characterized by a wall of hydrophobic polymer that surrounds their lipid core. The polymeric lipid wall of nanocapsules permits a sustain release of lipophilic compounds and protection of molecules encapsulated from photo-degradation phenomena (Dash and Konkimalla, 2012, Steelandt et al., 2014). The aim of this study was to compare the ability of SLN, NLC, NPLC and NC to entrap BP-3 minimalizing its penetration and permeation into living epidermis. All suspensions were characterized in terms of particle size, polydispersity index (PdI) and zeta potential. Moreover, in vitro sun protection factor (SPF) of the different suspensions was investigated. Cutaneous absorption data are discussed from granulometry analysis, encapsulating yield and SPF.

Section snippets

Materials

BP-3, poly-ε-caprolactone (MW: 45 kDa), phosphate buffered saline (PBS) tablets and chicken egg white albumin were purchased from Sigma Aldrich (St. Louis, Missouri, USA). Suppocire® AIML (Semi-synthetic glyceride base comprising saturated C8-C18 triglyceride fatty acids and lecithin), Plurol® oleique CC497 (polyglyceryl-6 dioleate, HLB 3) and Labrafil M1944CS® (mixture of mono-, di-, and triglycerides and mono- and di-fatty esters of polyethylene glycol 300, HLB 9) were gifts from Gattefossé

Results and discussion

Results of mean particle size, PdI and zeta potential of suspensions are showed in Table 4. All particle sizes are below 1 μm in a range comprised between 175 nm and 403 nm. SLN shows the largest particle size followed by NLC, NPLC and NC. All PdI values are comprised between 0.08 and 0.70 reflecting that sizes of each suspension are polydispersed. SLN suspension showed the largest size compared to the others suspensions that include liquid lipids into their core that decrease lipid matrix

Conclusion

The on-going protection concerns about UV radiation damages led to an increase of chemical UV filter use into sunscreen formulations. Therefore, innovative carriers for chemical UV filters are needed to formulate these molecules in a safer way avoiding their photo-degradation and preventing their permeation across the skin while maintaining high photoprotection efficiency. BP-3 skin permeation is known to trigger toxic effects in the organism. This study showed the interest of BP-3 entrapment

References (49)

  • J.P. Jee et al.

    Stabilization of all-trans retinol by loading lipophilic antioxidants in solid lipid nanoparticles

    Eur J. Pharm. Biopharm.

    (2006)
  • V. Jenning et al.

    Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids

    Int J. Pharm.

    (2000)
  • M.M. Jiménez et al.

    Influence of encapsulation on the in vitro percutaneous absorption of octyl methoxycinnamate

    Int. J. Pharm.

    (2004)
  • S. Kasichayanula et al.

    Percutaneous characterization of the insect repellent DEET and the sunscreen oxybenzone from topical skin application

    Toxicol. Appl. Pharmacol.

    (2007)
  • S. Kim et al.

    Effects of benzophenone-3 exposure on endocrine disruption and reproduction of Japanese medaka (Oryzias latipes) —a two generation exposure study

    Aquat. Toxicol.

    (2014)
  • J. Kuntsche et al.

    Interaction of lipid nanoparticles with human epidermis and an organotypic cell culture model

    Int. J Pharm.

    (2008)
  • Z. Lu et al.

    A method for the preparation of polymeric nanocapsules without stabilizer

    J. Control. Release

    (1999)
  • R.H. Müller et al.

    Nanostructured lipid matrices for improved microencapsulation of drugs

    Int. J. Pharm.

    (2002)
  • J.P. Mestres et al.

    Benzophenone-3 entrapped in solid lipid microspheres: formulation and in vitro skin evaluation

    Int. J. Pharm.

    (2010)
  • K. Morohoshi et al.

    Estrogenic activity of 37 components of commercial sunscreen lotions evaluated by in vitro assays

    Toxicol. In Vitro

    (2005)
  • T. Poiger et al.

    Occurrence of UV filter compounds from sunscreens in surface waters: regional mass balance in two Swiss lakes

    Chemosphere

    (2004)
  • C. Puglia et al.

    Lipid nanoparticles as carrier for octyl-methoxycinnamate: in vitro percutaneous absorption and photostability studies

    J. Pharm. Sci.

    (2012)
  • C. Puglia et al.

    Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies

    Eur. J. Pharm. Sci.

    (2014)
  • M. Schlumpf et al.

    Endocrine activity and developmental toxicity of cosmetic UV filters—an update

    Toxicology

    (2004)
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    These authors contributed equally to this work.

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