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Published on: February 23, 2018
Transdermal absorption of radioprotectors using permeation-enhancing vehicles
M Sodicoff1, A Lamperti, M C Ziskin
1Department of Anatomy, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Radiation Research
|February 1, 1990
Summary
Topical radioprotectors like WR-2721 can be effectively delivered to the skin using specific vehicles. This research shows that choosing the right formulation enhances radioprotector absorption through the skin
Area of Science:
- Pharmacology and Toxicology
- Dermatology
- Radiation Biology
Background:
- Clinical use of radioprotectors is limited by toxicity and concerns about protecting tumors.
- Topical radioprotection of skin, potentially with WR-2721, is a promising area, but previous studies using water-based solutions were ineffective.
- The stratum corneum presents a significant barrier to topical drug absorption.
Purpose of the Study:
- To investigate the skin absorption of radioprotectors (WR-2721 and cysteine) using various permeation-enhancing vehicles.
- To compare the absorption of radioprotectors in different vehicles versus water.
- To identify optimal vehicles for enhancing radioprotector penetration into and through the skin.
Main Methods:
- Radiolabeled WR-2721 and cysteine were dissolved in vehicles like dimethylformamide (DMF), propylene glycol, 2-pyrrolidone (2-P), methyl-2-pyrrolidone (M-2-P), and dimethylsulfoxide (DMSO).
- Absorption was studied through hairless mouse skin.
- Skin concentrations and plasma levels of the radioprotectors were measured to assess penetration.
Main Results:
- Dimethylformamide (DMF) most effectively increased WR-2721 concentration in the skin.
- Propylene glycol facilitated WR-2721 absorption into the dermis, indicated by plasma levels.
- DMF, 2-pyrrolidone (2-P), and methyl-2-pyrrolidone (M-2-P) improved skin cysteine levels, while dimethylsulfoxide (DMSO) increased plasma cysteine.
- Pre-treatment with DMSO enhanced WR-2721 skin concentration regardless of the vehicle.
- 2-P and DMF significantly increased plasma levels of WR-2721 (10- and 12-fold).
Conclusions:
- The choice of vehicle is critical for overcoming the stratum corneum barrier and enhancing topical radioprotector absorption.
- Specific vehicles like DMF and 2-P can significantly improve the penetration of radioprotectors into all skin layers.
- This approach holds potential for developing effective topical radioprotection strategies.
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