Synthesis of Polymer-Drug Conjugates for Transdermal Delivery of All-Trans Retinoic Acid (ATRA)
Abstract
Vitamin A and its derivatives are heavily used in the cosmetics industry to improve the appearance of skin discoloration, texture, as well as to treat skin disorders. Better known as retinoids, these substances are marketed for their anti-aging and anti-wrinkle effects. A common retinoid, all-trans retinoic acid (ATRA), generically known as tretinoin, has diverse biological activities including promoting keratinocyte proliferation, preventing trans epidermal water loss, inhibiting metalloproteinases, and stimulating angiogenesis within the dermis. Despite its various benefits, ATRA is often toxic and highly unstable in its natural form and as a result, is complexed with proteins or chemically conjugated to monomers to increase its stability. Currently, conventional formulations place ATRA as a bolus at the sight of interest, leading to increased irritability and proinflammatory responses due to immediate activation of retinoic acid receptors. Furthermore, multiple applications are required to maintain a therapeutic effect on the skin. Therefore, a clear limitation is observed for topical retinoid cosmetic formulations. New microparticle approaches for the topical administration of ATRA have been explored including the use of nanoparticles, liposomes, and polymeric micelles, to modulate the proliferation of skin cells. However, limited efforts exist determining how conjugations with biocompatible polymers, and more specifically how controlled polymerizations, can affect the formulation of a retinoid such as ATRA. This project aims to build on research for ATRA delivery systems using polymer-drug conjugates, specifically focusing on controlling the size of the polymeric micelle delivery system to better control the solubility, retention, and release profile of ATRA.
Faculty Sponsors
Dr. Patricia Calvo
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-5-2023 12:00 PM
End Date
4-6-2023 4:00 PM
Synthesis of Polymer-Drug Conjugates for Transdermal Delivery of All-Trans Retinoic Acid (ATRA)
Alvin Sherman Library
Vitamin A and its derivatives are heavily used in the cosmetics industry to improve the appearance of skin discoloration, texture, as well as to treat skin disorders. Better known as retinoids, these substances are marketed for their anti-aging and anti-wrinkle effects. A common retinoid, all-trans retinoic acid (ATRA), generically known as tretinoin, has diverse biological activities including promoting keratinocyte proliferation, preventing trans epidermal water loss, inhibiting metalloproteinases, and stimulating angiogenesis within the dermis. Despite its various benefits, ATRA is often toxic and highly unstable in its natural form and as a result, is complexed with proteins or chemically conjugated to monomers to increase its stability. Currently, conventional formulations place ATRA as a bolus at the sight of interest, leading to increased irritability and proinflammatory responses due to immediate activation of retinoic acid receptors. Furthermore, multiple applications are required to maintain a therapeutic effect on the skin. Therefore, a clear limitation is observed for topical retinoid cosmetic formulations. New microparticle approaches for the topical administration of ATRA have been explored including the use of nanoparticles, liposomes, and polymeric micelles, to modulate the proliferation of skin cells. However, limited efforts exist determining how conjugations with biocompatible polymers, and more specifically how controlled polymerizations, can affect the formulation of a retinoid such as ATRA. This project aims to build on research for ATRA delivery systems using polymer-drug conjugates, specifically focusing on controlling the size of the polymeric micelle delivery system to better control the solubility, retention, and release profile of ATRA.
