4′-OH as the Action Site of Lipids and MRP1 for Enhanced Transdermal Delivery of Flavonoids

Abstract

To date, the transdermal delivery study mainly focused on the drug delivery systems' design and efficacy evaluation. Few studies reported the structure− affinity relationship of the drug with the skin, further revealing the action sites of the drugs for enhanced permeation. Flavonoids attained a considerable interest in transdermal administration. The aim is to develop a systematic approach to evaluate the substructures that were favorable for flavonoid delivery into the skin and understand how these action sites interacted with lipids and bound to multidrug resistance protein 1 (MRP1) for enhanced transdermal delivery. First, we investigated the permeation properties of various flavonoids on the porcine skin or rat skin. We found that 4′-OH (hydroxyl group on the carbon 4′ position) rather than 7-OH on the flavonoids was the key group for flavonoid permeation and retention, while 4′-OCH 3 and −CH 2 �CH 2 − CH−(CH 3 ) 2 were unfavorable for drug delivery. 4′-OH could decrease flavonoids' lipophilicity to an appropriate log P and polarizability for better transdermal drug delivery. In the stratum corneum, flavonoids used 4′-OH as a hand to specifically grab the C�O group of the ceramide NS (Cer), which increased the miscibility of flavonoids and Cer and then disturbed the lipid arrangement of Cer, thereby facilitating their penetration. Subsequently, we constructed overexpressed MRP1 HaCaT/MRP1 cells by permanent transfection of human MRP1 cDNA in wild HaCaT cells. In the dermis, we observed that 4′-OH, 7-OH, and 6-OCH 3 substructures were involved in H-bond formation within MRP1, which increased the flavonoid affinity with MRP1 and flavonoid efflux transport. Moreover, the expression of MRP1 was significantly enhanced after the treatment of flavonoids on the rat skin. Collectively, 4′-OH served as the action site for increased lipid disruption and enhanced affinity for MRP1, which facilitate the transdermal delivery of flavonoids, providing valuable guidelines for molecular modification and drug design of flavonoids.

Cu+-doped lead-free double perovskite quantum dots for enhancing the photovoltaic performance of carbon-based Cs2AgInCl6 perovskite solar cells

“…However, the decrease in PL with a higher Cu + content may be due to more defect states being introduced by a large amount of Cu + ions. [21][22][23] The fabricated C-based PSCs with stacked configuration and the corresponding cross-sectional SEM image of ITO/SnO 2 / Cs 2 AgInCl 6 //C are shown in Fig. 4a, for the device composed of a photoanode (ITO/SnO 2 /Cs 2 AgInCl 6 ) and back electrode (C electrode).…”

Doping strategies for inorganic lead-free halide perovskite solar cells: progress and challenges

“…The application of additives is very effective in improving the film quality. Fan et al 109 greatly improved the film quality of Cs 2 AgBiBr 6 by using carbohydrazide (CBH) as an additive. Adding CBH during the crystallization process leads to the formation of pinhole-free thin films and reduces the defect density, which suppresses carrier recombination.…”

“…Fig.9(a) Mechanism for Cs 2 AgBiBr 6 film formation assisted by a thiourea additive 110. (b) Structure and J-V curves of Cs 2 AgBiBr 6 PSCs with and without 10 mg mL À1 CBH 109. (c) Top-view surface morphology structure and PCE distributions of control Cs 2 AgBiBr 6 and Cs 2 AgBiBr 6 -1.0MABr 111.…”

Tailoring the Chemisorption Manner of Fe d‐Band Center with La2O3 for Enhanced Oxygen Reduction in Anion Exchange Membrane Fuel Cells

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