Formulation and Skin Permeation of Active-Loaded Lipid Nanoparticles: Evaluation and Screening by Synergizing Molecular Dynamics Simulations and Experiments
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Formulation and Skin Permeation of Active-Loaded Lipid Nanoparticles: Evaluation and Screening by Synergizing Molecular Dynamics Simulations and Experiments
Formulation and Skin Permeation of Active-Loaded Lipid Nanoparticles: Evaluation and Screening by Synergizing Molecular Dynamics Simulations and Experiments
Gupta, K. M., Das, S., Wong, A. B. H., & Chow, P. S. (2022). Formulation and Skin Permeation of Active-Loaded Lipid Nanoparticles: Evaluation and Screening by Synergizing Molecular Dynamics Simulations and Experiments. Langmuir, 39(1), 308–319. https://doi.org/10.1021/acs.langmuir.2c02550
Abstract:
Encapsulation into nanoparticles (NPs) is a potential method to deliver
pharmaceutical/cosmetic actives deep into the skin. However, understanding of NP formulations and
underlying mechanism of active delivery to skin has scarcely been studied. We report a simulation
platform that screens, evaluates, formulates, and provides atomic-resolution interpretation of NP-based
formulations, and reveal active permeation mechanism from NPs to skin. First, three actives namely
ferulic acid (FA), clotrimazole (CZE) and tretinoin (TTN), and five lipid excipients (Compritol, Precirol,
Geleol, Gelot, Gelucire) combinations were screened by MD simulations for the best pairs. For each
suggested pair, actual active and lipid compositions for the synthesis of stable NP formulations were then
obtained by experiments. MD simulations demonstrate that in NP formulations, FA and CZE actives are
present at the surface of the NPs, whereas TTN molecules are present at both the surface and interior of
the NP core. The NP shapes obtained by simulation perfectly match with experiments. For each NP,
separate MD simulations illustrate that active-loaded NPs approach the skin surface quickly, then actives
translocate from NP surface to skin surface followed by penetration of NPs through skin. The driving
force for the translocation which initiates during the penetration process, is the stronger active-skin
interaction compared to active-NP interaction. Permeation free energy indicates spontaneous transfer of
actives from solution phase to the surface of skin bilayer. The free energy barriers are increased in the
order of FA < TTN < CZE. Significantly lower diffusions of actives are obtained in the main barrier
region compared to bulk, and the average diffusion coefficients of actives are in the same order of
magnitude (~ 10-6 cm2/s). The estimated permeability coefficients (log P) of actives are mainly governed
by free energy barriers. The study would facilitate the development of novel lipid-based NP formulations
for personal-care/pharmaceutical applications.
License type:
Publisher Copyright
Funding Info:
This research is supported by core funding from: Institute of Sustainability for Chemicals, Energy and Environment, A*STAR
Grant Reference no. : SC22/20-1A0120-0AAK