Research Articles
Preparation of polymeric nanocapsules containing octyl methoxycinnamate by the emulsification–diffusion technique: Penetration across the stratum corneum

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Abstract

Polymeric nanocapsules (NCs) containing octyl methoxycinnamate (OMC) as lipophilic molecule were prepared, and their in vivo distribution profile through the stratum corneum (SC) was determined by the tape-stripping technique. Penetration degree of OMC formulated in NCs was compared with that obtained for a nanoemulsion (NE), and a conventional oil-in-water (o/w) emulsion (EM). To produce stable cellulose acetate phthalate (CAP) nanocapsules containing the lipophilic sunscreen, a study was conducted to optimize the process of NC preparation based on the emulsification–diffusion technique. NC formation was verified by measuring their density using differential centrifugation. NC density revealed that an OMC (µL)/CAP (mg) ratio of 2.5:1 is optimal for encapsulation. High encapsulation entrapment (>96%) and excellent process efficiency (recovered quantity of NCs in relation with the initial amount of OMC and CAP >99%) were always achieved with this ratio or a higher one. The capsular structure of the NCs was evidenced with a direct SEM technique. NE was prepared by the emulsification–diffusion technique, dissolving a specific quantity of OMC in water-saturated 2-butanone and then, emulsifying with an aqueous solution of PVAL. In vivo percutaneous penetration, evaluated by the tape-stripping technique, demonstrated that NE increased the extent of OMC penetration relative to the penetration achieved by NCs or EM, with relative penetration depths through the SC of 0.86 ± 0.1, 0.64 ± 0.11, and 0.57 ± 0.08, respectively. In the same manner, the accumulation in the skin of OMC was significantly greater with NE than with EM or NCs. OMC penetration depth was strongly dependent upon the size of the colloidal particles and their flexibility. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.

Section snippets

INTRODUCTION

For many years, topical sunscreens have been recommended as a useful way to provide protection to human skin against acute and chronic adverse effects of solar radiation.1., 2., 3., 4. As we know, sunscreens basically alter the optical properties of the skin. They produce a protective layer on the skin in which UV light is either absorbed by organic compounds that absorb UV in the appropriate wavelength range (UV filters); scattered and reflected by inorganic micropigments (titanium oxide); or

Materials

Octyl methoxycinnamate (OMC) was supplied by Multiquim S.A., Mexico City, Mexico. Analytical grade 2-butanone was obtained from Fluka, Buchs, Switzerland. Cellulose acetate phthalate (CAP) was purchased from Vita Drug S.A. (Mexico City, Mexico). The non-ionic stabilizing agent was poly(vinyl alcohol) (PVAL; Mowiol 4-88, Mw: 26000; Glomarza, Mexico City, Mexico). Scotch Book Tape 845 was purchased from 3M (St. Paul, MN). Filter membranes (pore diameter 0.22 µM) were obtained from Millipore

Characterization of Formulations

In this study, the emulsification–diffusion method24 was appropriate for the preparation of mononuclear NCs and a NE containing octyl methoxycinnamate. As shown in Table 1, the incorporation of sunscreen into all the polymeric particles prepared was 96% successful at ratios of 1.0:1.0 and 2.5:1.0. On the other hand, only partial encapsulation (∼61%) of the oil was achieved for the 4.0:1.0 ratio, due to the excess of oil. In terms of process efficiency, almost the entire polymer transformed into

CONCLUSIONS

We have demonstrated that the emulsification–diffusion technique is useful in the preparation of NCs containing octyl methoxycinnamate with a high encapsulation rate and high process efficiency. An OMC (µL)/CAP (mg) ratio of 2.5:1.0 was optimal for encapsulation (particle size of 458.3 ± 0.5 nm). Visualization of the capsular structure of NCs was successfully examined by SEM using osmium tetroxide as staining agent, avoiding in this way the use of freeze-fracture.

Incorporation of OMC in NE

Acknowledgements

The authors acknowledge the financial support for this work from CONACYT (Ref. J27741-M) and PAPIIT (Ref. IN214000). We are thankful to Mr. Rodolfo Robles for his technical assistance with the SEM.

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