# MECHANISTIC STUDIES OF TRANSDERMAL TRANSPORT/METABOLISM

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 1994 · $258,750

## Abstract

Optimal design of efficacious transdermal delivery systems requires an
understanding of transport mechanism(s) through skin, especially the
stratum corneum barrier, and potential drug metabolism in the presence of
the vehicles.  While the immediate goal is directed toward understanding
the mechanism(s) of solvent-enhanced percutaneous absorption of steroids,
topical and transdermal system development for growth factors,
polypeptides or other pharmaceutical agents would also benefit from a
delivery mode that takes advantage of controlled delivery and by-passing
first past metabolism.  Solvent-mediated percutaneous enhancement
mechanisms derived from proposed investigation will provide a systematic
understanding of how common solvents employed in most formulations alter
permeation pathways and barriers as a function of solvent chemical
structure and physicochemical parameters.  Such knowledge will provide a
rational basis for formulation of a wide variety of topical and
transdermal pharmaceutical systems.  The working hypothesis is that there
are two competing mechanisms of solvent-mediated enhanced permeation: 1)
increased solubility of the solute within the vehicle or skin and 2)
solvent-induced alterations of the stratum corneum membrane.  The first
mechanism is believed to be the primary mechanism for lipophilic solute
permeation, while the second mechanism is believed to dominate for more
hydrophilic solute permeation.  Hence, proposed studies focus on
elucidating penetration enhancer effects on the heterogeneous lipid
domain, polar head regions and intracellular keratinized and cell
envelope proteins within the stratum corneum; and then subsequent
correlations of these biophysical alterations with in vitro and in vivo
transport and metabolism across the skin.  This will be achieved with the
specific aims using an iterative process of probing vehicle effects on 1)
solute solubility and uptake, 2) in vitro and in vivo transport via
lipophilic and polar pathways and 3) alterations of biophysical
structures characteristic of lipophilic and polar pathways and barriers
of the stratum corneum, and 4) refinement of the mechanisms for
solvent-mediated percutaneous transport and metabolism.

## Key facts

- **NIH application ID:** 2198741
- **Project number:** 5R01HD023000-07
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **SAM.gov UEI:** LL8GLEVH6MG3
- **Principal Investigator:** KRISTINE KNUTSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $258,750
- **Award type:** 5
- **Project period:** 1987-04-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198741

## Citation

> US National Institutes of Health, RePORTER application 2198741, MECHANISTIC STUDIES OF TRANSDERMAL TRANSPORT/METABOLISM (5R01HD023000-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198741. Licensed CC0.

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