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Biomedical subjects

Ruby Ghadially

Publications and source records attributed to Ruby Ghadially.

4 recordsLinked to original sources

A new water-based topical carrier with polar skin-lipids.

A new water-based topical formulation is presented that aims at providing good penetration properties for both lipophilic and hydrophilic drugs with as small a disturbance of the skin barrier function as possible. The formulation contains dispersed lipids in a ratio resembling that of human skin. The capacity to deliver is addressed in this first study while the mild effect on skin will be presented later. Three variations of the lipid formulation were investigated by use of pigskin in vitro diffusion cell. The hydrophilic 5(6)-carboxyfluorescein (CF) and the lipophilic acridine orange 10-nonyl bromide (AO) were used as model drug substances. The results showed that the delivery properties of the new formulation exceeded that of the references (vaseline and xanthan gum gel). The effect was largest for lipophilic AO where all lipid matrix formulations were superior in amount detected in the skin. The results for the hydrophilic CF were also promising. Especially efficient was the lipid formulation containing the non-ionic adjuvants tetra ethylene glycol monododecyl ether and polyoxyethylene 23 dodecyl ether. The additional in vivo study suggests that the used in vitro model has qualitative bearing on relevant in vivo situations.

Acridine Orange↗

Imiquimod-induced interleukin-1 alpha stimulation improves barrier homeostasis in aged murine epidermis.

In response to acute disruption of the permeability barrier of aged mammals there is a diminished capacity for barrier recovery, analogous to other aged organs when stressed. Acute barrier disruption increases levels of epidermal cytokines, and cytokines are known regulators of keratinocyte mitogenesis, as well as lipid synthesis in extracutaneous tissues. Underlying the sluggish barrier recovery in aged skin are diminished mRNA and protein levels for the interleukin-1 cytokine family, and its receptors. To further elucidate the role of the interleukin-1 family of cytokines in the barrier repair response, cytokine production was stimulated in aged murine skin with topical imiquimod application. Imiquimod accelerated barrier recovery after acute insults to aged and young skin. These functional results correlated temporally with increased interleukin-1 alpha production in the epidermis following topical imiquimod administration to murine skin. Furthermore, intracutaneous injections of interleukin-1 alpha accelerated barrier recovery in aged mice. Finally, we showed that interleukin-1 alpha added to cultured human keratinocytes stimulates epidermal lipid synthesis. These studies provide further evidence for the role of reduced interleukin-1 alpha signaling in the decline of permeability barrier function in aged skin, and point to the potential use of cytokine augmentation in barrier dysfunction of the aged.

Adjuvants, Immunologic↗

The aged epidermal permeability barrier: basis for functional abnormalities.

Aged epidermis develops an abnormality in permeability barrier homeostasis, which is accentuated further in photoaged skin. The biochemical basis is a global reduction in stratum corneum lipids and profound abnormality in cholesterol synthesis. Various cytokine/growth factor signaling pathways are abnormal in aged skin, particularly in the interleukin-1 family. Barrier repair therapy can be effective in restoring normal function if a cholesterol-dominant mixture of the three key physiologic lipids, including ceramides and free fatty acids, is emphasized.

Aged↗