Effect of phloretin on the percutaneous absorption of lignocaine across human skin

Valenta, Claudia; Cladera, Josep; O’Shea, Paul; Hadgraft, Jonathan

doi:10.1002/1520-6017(200104)90:4<485::aid-jps1006>3.0.co;2-#

Cited by 41 publications

(15 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because phloretin has been suggested as a penetration enhancer for transdermal drug delivery (27)(28)(29)(30)(31), and was shown to propagate systemically in rodents after local skin-based administration (28), we have evaluated phloretin as a potential transdermal therapeutic transgene expression inducer. Therefore, we have microencapsulated CHO-PEACE 8 in coherent alginate-PLL-alginate capsules and implanted them s.c. into mice.…”

Section: Phloretin-mediated Transdermal Gene Expression In Sc Implamentioning

confidence: 99%

“…Phloretin has been studied as a possible penetration enhancer for skin-based drug delivery (27)(28)(29)(30)(31), attenuates inflammation by antagonizing prostaglandins (32), protects the skin from UV light-induced photodamage (33,34), and is currently evaluated as a chemopreventive agent for cancer treatment (35). Because the plant rhizosphere is one of the natural habitats of Pseudomonas putida (strain DOT-T1E), this prokaryote has evolved the RND family transporter TtgABC with multidrug recognition properties, which is controlled by its cognate repressor TtgR binding to a specific operator (O TtgR ) in the TtgR promoter (P TtgR ).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin

Gitzinger

Kemmer

El‐Baba

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

109

View full text Add to dashboard Cite

Adjustable control of therapeutic transgenes in engineered cell implants after transdermal and topical delivery of nontoxic trigger molecules would increase convenience, patient compliance, and elimination of hepatic first-pass effect in future therapies. Pseudomonas putida DOT-T1E has evolved the flavonoid-triggered TtgR operon, which controls expression of a multisubstrate-specific efflux pump (TtgABC) to resist plant-derived defense metabolites in its rhizosphere habitat. Taking advantage of the TtgR operon, we have engineered a hybrid P. putida-mammalian genetic unit responsive to phloretin. This flavonoid is contained in apples, and, as such, or as dietary supplement, regularly consumed by humans. The engineered mammalian phloretin-adjustable control element (PEACE) enabled adjustable and reversible transgene expression in different mammalian cell lines and primary cells. Due to the short half-life of phloretin in culture, PEACE could also be used to program expression of difficult-to-produce protein therapeutics during standard bioreactor operation. When formulated in skin lotions and applied to the skin of mice harboring transgenic cell implants, phloretin was able to fine-tune target genes and adjust heterologous protein levels in the bloodstream of treated mice. PEACE-controlled target gene expression could foster advances in biopharmaceutical manufacturing as well as gene-and cell-based therapies.synthetic biology ͉ synthetic gene networks ͉ transdermal gene regulation ͉ gene therapy ͉ biopharmaceutical manufacturing

show abstract

Section: Phloretin-mediated Transdermal Gene Expression In Sc Implamentioning

confidence: 99%

mentioning

confidence: 99%

Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin

Gitzinger

Kemmer

El‐Baba

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

109

View full text Add to dashboard Cite

show abstract

“…Considering that many of the drugs of interest for transdermal delivery have a molecular structure, which bears a net electrical charge, or chemical groups that are electrical dipoles, one possible way to enhance the penetration of such molecules would be by modifying the electrical properties of the stacked lipid bilayers of the stratum corneum. The interaction of charged molecules with and translocation through model lipid bilayers is known to be affected, for example, by variations of the so‐called membrane dipole potential, and we have recently shown how phloretin, a compound known to decrease the membrane dipole potential,11–13 enhances the transdermal delivery of the local anesthetic lignocaine hydrochloride 14…”

Section: Introductionmentioning

confidence: 99%

Differential expression of calretinin and metabotropic glutamate receptor mGluR1α defines subsets of unipolar brush cells in mouse cerebellum

Nunzi¹,

Shigemoto²,

Mugnaini³

2002

J of Comparative Neurology

106

115

View full text Add to dashboard Cite

The unipolar brush cell (UBC) is a type of glutamatergic interneuron in the granular layer of the cerebellum. The UBC brush and a single mossy fiber (MF) terminal contact each other within a cerebellar glomerulus, forming a giant synapse. Many UBCs receive input from extrinsic MFs, whereas others are innervated by intrinsic mossy terminals formed by the axons of other UBCs. In all mammalian species so far examined, the vestibulocerebellum is enriched of UBCs that are strongly immunoreactive for the calcium binding protein calretinin (CR) in both the somatodendritic and axonal compartment. UBCs have postsynaptic ionotropic glutamate receptors and extrasynaptic metabotropic glutamate receptors that immunocytochemically highlight their somatodendritic compartment and brush, respectively. In this study on the mouse cerebellum, we present evidence that immunoreactivities to CR and mGluR1alpha define two distinct UBC subsets with partly overlapping distributions in lobule X (the nodulus). In sections double-labeled for CR and mGluR1alpha, the patterns of distributions of CR(+)/mGluR1alpha(-) UBCs and CR(-)/mGluR1alpha(+) UBCs differed along the mediolateral and dorsoventral axes of the folium. Moreover, mGluR1alpha(+) UBCs outnumbered CR(+) UBCs. Both UBC subsets were mGluR2/3, GluR2/3, and NMDAR1 immunoreactive. The different distribution patterns of the two UBC subsets within lobule X suggest that expression of CR or mGluR1alpha by UBCs may be afferent-specific and related to the terminal fields of different vestibular MF afferents.

show abstract

“…Limonene, menthone, and eugenol were found to enhance transdermal absorption of tamoxifen (41). Phloretin, a polyphenol, enhanced the penetration of lignocaine (42). In general, absorption enhancement research into the enhancement of percutaneous penetration has been done with animal skin (pig or rabbit) or human skin obtained from cadavers or plastic surgery procedures.…”

Section: Technical Considerationsmentioning

confidence: 99%

Delivering drugs by the transdermal route: review and comment

Tanner¹,

Marks²

2008

Skin Research and Technology

225

112

View full text Add to dashboard Cite

Background: There are many advantages to administering drugs by routes that bypass the gastrointestinal tract. One such route is the transdermal in which the drug agent is applied to the skin in a patch or device of some type so that sufficient quantity penetrates the skin to exert a systemic effect. There are several theoretical advantages to this approach not the least of which is that the drug avoids being metabolized by the liver after absorption and that gastrointestinal irritation is avoided. Aims: To discuss the various ways in which drugs can be persuaded to cross the skin barrier and also to discuss the

show abstract

Effect of phloretin on the percutaneous absorption of lignocaine across human skin

Cited by 41 publications

References 26 publications

Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin

Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin

Differential expression of calretinin and metabotropic glutamate receptor mGluR1α defines subsets of unipolar brush cells in mouse cerebellum

Delivering drugs by the transdermal route: review and comment

Contact Info

Product

Resources

About