To investigate the use of chitosan nanoparticles (CS-TPP-NPs) as carriers for α- and β-arbutin. In this study, CS-TPP-NPs containing α- and β-arbutin were prepared via the ionic cross-linking of CS and TPP and characterized for particle size, zeta potential, and dispersity index. The entrapment efficiency and loading capacity of various β-arbutin concentrations (0.1, 0.2, 0.4, 0.5, and 0.6%) were also investigated. SEM, TEM FTIR, DSC and TGA analyses of the nanoparticles were performed to further characterize the nanoparticles. Finally, stability and release studies were undertaken to ascertain further the suitability of the nanoparticles as a carrier system for α- and β-arbutin. Data obtained clearly indicates the potential for use of CS-TPP-NPs as a carrier for the delivery of α- and β-arbutin. The size obtained for the alpha nanoparticles (α-arbutin CSNPs) ranges from 147 to 274 d.nm, with an increase in size with increasing alpha arbutin concentration. β-arbutin nanoparticles (β-arbutin CSNPs) size range was from 211.1 to 284 dn.m. PdI for all nanoparticles remained between 0.2-0.3 while the zeta potential was between 41.6-52.1 mV. The optimum encapsulation efficiency and loading capacity for 0.4% α-arbutin CSNPs were 71 and 77%, respectively. As for β-arbutin, CSNP optimum encapsulation efficiency and loading capacity for 0.4% concentration were 68 and 74%, respectively. Scanning electron microscopy for α-arbutin CSNPs showed a more spherical shape compared to β-arbutin CSNPs where rod-shaped particles were observed. However, under transmission electron microscopy, the shapes of both α- and β-arbutin CSNP nanoparticles were spherical. The crystal phase identification of the studied samples was carried out using X-ray diffraction (XRD), and the XRD of both α and β-arbutin CSNPs showed to be more crystalline in comparison to their free form. FTIR spectra showed intense characteristic peaks of chitosan appearing at 3438.3 cm (-OH stretching), 2912 cm (-CH stretching), represented 1598.01 cm (-NH) for both nanoparticles. Stability studies conducted for 90 days revealed that both α- and β-arbutin CSNPs were stable in solution. Finally, release studies of both α- and β-arbutin CSNPs showed a significantly higher percentage release in comparison to α- and β-arbutin in their free form. Chitosan nanoparticles demonstrate considerable promise as a carrier system for α- and β-arbutin, the use of which is anticipated to improve delivery of arbutin through the skin, in order to improve its efficacy as a whitening agent.

Background: There has been an increase in demand for cosmetic skin-whitening products with efficacy toward lightening skin tone. β-arbutin is an inhibitor of tyrosinase enzyme activity within the skin’s melanocytes, and so has shown considerable promise as a skin-lightening agent. It is, however, both hydrophilic and hygroscopic, which hinders its penetration of the skin to reach these melanocytes. Chitosan (CS) possesses considerable penetration-enhancing properties when utilized in topical delivery formulations. The strong affinity of positively charged chitosan nanoparticles toward negatively charged biological membranes can be exploited to achieve site-specific targeting. Objective: To investigate the use of chitosan nanoparticles (CSNPs) as carrier units to enhance the topical delivery of β-arbutin. Method: CSNPs containing β-arbutin were prepared using an ionic cross-linking method, and entrapment efficiency and loading capacity were evaluated at numerous β-arbutin concentrations. Further characterization involved using FTIR, XRD, TEM, and TGA, and in vitro permeation studies were conducted using in vitro Franz diffusion cells. Results: β-arbutin chitosan nanoparticles were successfully formulated with a size range of 211–289 d.nm, a polydispersity index between 0.2–0.3, and zeta potential in the range 46.9–64.0 mV. The optimum encapsulation efficiency (EE) and loading capacity (LC) of β-arbutin were 68% and 73%, respectively. TEM revealed the nanoparticles to be spherical in shape. FTIR spectra revealed characteristic chitosan-related peaks appearing at 3438.3 cm−1 (-OH stretching) and 3320 cm−1 (-CH stretching), together with 1598.01 cm−1 (-NH2) specific to β-arbutin nanoparticles. XRD analysis revealed an increase in crystallinity and TGA analyses identified increasing thermal stability with increasing β-arbutin concentration. In vitro studies indicated higher permeation and improved penetration of β-arbutin loaded in CSNPs compared to its free form. Conclusion: CSNPs present considerable promise as effective carriers for improved topical delivery of β-arbutin.