(T1330-08-48) Investigation of the Transdermal Delivery of Mangiferin Loaded Starch Nanoparticles

Purpose: The purpose of the study was to evaluate the in vitro skin penetration of mangiferin loaded starch nanoparticles. Mangiferin, a bioactive compound found in mango, exhibits a wide range of potential applications, particularly in skincare, cancer prevention and treatment, and managing metabolic and inflammatory diseases. Mangiferin belongs to class IV of the Biopharmaceutics Classification System (BCS) of drugs with low solubility and low permeability. Therefore, this study aims to develop starch nanoparticles containing mangiferin using mild alkali hydrolysis and ultrasonication to improve its solubility and skin permeability.

Methods: Starch nanoparticles were prepared via a modified ultra-sonication method based on Ahmad et al. (2019b). A 1.5% starch suspension was preheated to 80 °C in 0.1 M NaOH and stirred for 30 min. Mangiferin (0.2mg/ml) was dissolved in ethanol and added dropwise to the hot starch slurry (1:10 ratio) and stirred for another 30 min until ethanol had completely evaporated. To enhance mangiferin encapsulation, the mixture was ultrasonicated at 60 kHz for 30 min using a fixed probe sonicator (Branson SFX150 Sonifier, USA), applied in 3-minute intervals to prevent overheating. The final solution was freeze-dried using Freeze dryer (Labconco, Kansas City, MO, USA) to obtain mangiferin loaded nanoparticle powder, which was stored at 4 °C. The prepared nanoparticles were tested for particle size, polydispersity index using Zeta sizer (Nano ZX, Malvern, UK.), % Encapsulation Efficiency, and in vitro permeation. Permeation testing was performed using dermatomed human cadaver skin obtained from an accredited U.S. tissue bank (Science Care,Folcroft, PA,19032). Non-occluded vertical glass Franz diffusion cell (FDC) equipment was used with receptor volumes of 5 mls (Logan, NJ). Two formulations with (n = 3 for each group). A sample of 500 µl of each formulation was applied to each donor compartment (0.64 cm²) of each Franz cell. During the skin permeation study, the skin temperature was maintained at 32˚C. Skin sample integrity was recorded using Trans Epidermal Water Loss (TEWL) measurements before and after the permeation study. At 24 hours, samples were taken of the receptor, and then after 24 hours, the receptor, epidermis, and dermis drug content were quantified using the previously validated HPLC assays for mangiferin.

Results: The average particle size of drug loaded nanoparticles was found to be 58.85±0.80 nm with a polydispersity index of 0.24±0.01. The % encapsulation efficiency of mangiferin loaded nanoparticles was found to be 72.34% ± 4.53. The amount of drug permeated after 24 hours in the receptor compartment of mangiferin nanoparticles and ethanolic drug solution was found to be 52.35 µg/cm² and 2.15 µg/cm². The amount of mangiferin found in the epidermis was higher for nanoparticles (0.10 ± 0.02 µg/mg) compared to the ethanolic solution (0.010 ± 0.001µg/mg), indicating improved skin penetration. Similarly, the drug concentration in the dermis was greater for nanoparticles (0.01 ± 0.00 µg/mg) than the ethanolic solution (0.00 ± 0.00 µg/mg), highlighting the enhanced transdermal delivery of mangiferin starch nanoparticles.

Conclusion: Mangiferin-loaded starch nanoparticles demonstrated improved drug encapsulation, uniform particle size distribution, and significantly enhanced transdermal delivery compared to the ethanolic drug solution. The formulation showed superior skin penetration and retention in both the epidermis and dermis, highlighting its potential as an effective transdermal drug delivery system.

References: (1) Pleguezuelos-Villa, M.; Nácher, A.; Hernández, M.; Buso, M. O. V.; Sauri, A. R.; Díez-Sales, O. Mangiferin nanoemulsions in treatment of inflammatory disorders and skin regeneration. International Journal of Pharmaceutics 2019, 564, 299–307.
(2) Hering, A.; Ochocka, J. R.; Baranska, H.; Cal, K.; Stefanowicz-Hajduk, J. Mangiferin and hesperidin transdermal distribution and permeability through the skin from solutions and honeybush extracts (Cyclopia sp.)—A comparison ex vivo study. Molecules 2021, 26 (21), 6547.
(3) Sguizzato, M.; Ferrara, F.; Hallan, S. S.; Baldisserotto, A.; Drechsler, M.; Malatesta, M.; Costanzo, M.; Cortesi, R.; Puglia, C.; Valacchi, G. Ethosomes and transethosomes for mangiferin transdermal delivery. Antioxidants 2021, 10 (5), 768.

Acknowledgements: Funding for conducting this research was provided by the Center for Dermal Research, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854.

Figure 1: Schematic illustration of in vitro permeation study of mangiferin nanoparticles.

Figure 2: In vitro permeation study results