The use of nanoencapsulation to decrease human skin irritation caused by capsaicinoids

Abstract

Capsaicin, a topical analgesic used in the treatment of chronic pain, has irritant properties that frequently interrupt its use. In this work, the effect of nanoencapsulation of the main capsaicinoids (capsaicin and dihydrocapsaicin) on skin irritation was tested in humans. Skin tolerance of a novel vehicle composed of chitosan hydrogel containing nonloaded nanocapsules (CH-NC) was also evaluated. The chitosan hydrogel containing nanoencapsulated capsaicinoids (CH-NC-CP) did not cause skin irritation, as measured by an erythema probe and on a visual scale, while a formulation containing free capsaicinoids (chitosan gel with hydroalcoholic solution [CH-ET-CP]) and a commercially available capsaicinoids formulation caused skin irritation. Thirty-one percent of volunteers reported slight irritation one hour after application of CH-NC-CP, while moderate (46% [CH-ET-CP] and 23% [commercial product]) and severe (8% [CH-ET-CP] and 69% [commercial product]) irritation were described for the formulations containing free capsaicinoids. When CH-NC was applied to the skin, erythema was not observed and only 8% of volunteers felt slight irritation, which demonstrates the utility of the novel vehicle. A complementary in vitro skin permeation study showed that permeation of capsaicinoids through an epidermal human membrane was reduced but not prevented by nanoencapsulation.

Keywords: capsaicinoids; chitosan; nanocapsules; skin irritation; skin permeation.

Figures

Figure 1

Viscosity as a function of shear rate of (A) chitosan hydrogels containing nanocapsules and (B) chitosan hydrogels containing ethanol and a commercial formulation of capsaicinoids. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids; ET, ethanolic solution; Commercial, commercial formulation.

Figure 2

Size distribution analyses of chitosan hydrogels containing nanocapsules. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids.

Figure 3

Skin erythema measured by electronic probe. The results indicate a ratio between the initial values (before application of formulation) and the final value at every measuring time point. Notes: Significant differences observed (P<0.05): *CH-ET-CP versus no formulation; **commercial formulation versus no formulation. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids; ET, ethanolic solution; Commercial, commercial formulation.

Figure 4

Skin erythema measured by a visual scale. Notes: Significant differences observed (P<0.05): *CH-ET-CP versus no formulation; **commercial formulation versus no formulation. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids; ET, ethanolic solution; Commercial, commercial formulation.

Figure 5

Arm of a volunteer 90 minutes after application of the formulations. The photograph is representative of the entire experiment. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids; ET, ethanolic solution; Commercial, commercial formulation.

Figure 6

Skin pH (A) and transepidermal water loss (B) measured by electronic probe. The results indicate a ratio between the initial values (before application of formulation) and the final value at every measuring time point. Note: No significant differences (P<0.05) are observed between areas with and without application of the formulations. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids; ET, ethanolic solution; Commercial, commercial formulation.

Figure 7

Skin permeation of capsaicinoids incorporated in different semisolid formulations. Note: Significant differences are described in Table 3. Abbreviations: CH, chitosan gel; NC, nanocapsules; CP, capsaicinoids; ET, ethanolic solution; Commercial, commercial formulation.