TPM® – Overview of Delivery Technology

TPM®, known as Targeted Penetration Matrix, is a multi-functional and multi-component delivery technology invented at Phosphagenics. The abbreviation TPM also stands for ‘tocopheryl phosphate mixture’ as it is composed of two different forms of phosphorylated Vitamin E (mono-a-tocopheryl phosphate, TP & di-a-tocopheryl phosphate, T2P). Phosphagenics discovered that TP is a naturally occurring form of Vitamin E, present in animal tissues and plants1-3. Whereas Vitamin E is an oil with very poor solubility in water, the addition of a phosphate group makes the TPM® molecules amphiphilic, meaning that they have solubility in both water and oil. This is important because the skin has both oil and water layers. Therefore, TPM®has increased solubility within the skin compared to standard Vitamin E, and is able to diffuse more efficiently.

TPM® is a scientifically validated delivery technology generating reproducible results across multiple clinical trials. It has proven capacity to deliver both small and large molecules, in addition to being a non-invasive and non-irritating system. Some molecules that we have delivered transdermally using TPM® include oxymorphone, oxycodone, lidocaine, diclofenac, ibuprofen, tretinoin, and even insulin. Unlike any other penetration enhancement system, TPM®can be modulated to control the rate and location of delivery, and enhance compatibility with molecules of widely different chemistries. TPM® can be formulated into a gel, patch, cream or spray system offering various dosage forms to suit specific indications.

Because TPM® is built from Vitamin E, it is able to soothe the skin and reduce irritation that may be caused by the active ingredients that it delivers (e.g., tretinoin). Other delivery systems, such as those based on liposomes, are built from inert phospholipids and/or surfactants. Unlike TPM®, their role is purely one of delivery, and they do not have any intrinsic properties of reducing irritation.

1. a-tocopheryl phosphate: A novel, natural form of vitamin E. Free Radical Biology & Medicine. (2005) 39:970-976.
2. On the existence of cellular tocopheryl phosphate, its synthesis, degradation and cellular roles: A Hypothesis. IUBMB Life. (2005) 57(1):23-25.
3. Modulation of cell proliferation and gene expression by a-tocopheryl phosphates: relevance to atherosclerosis and inflammation. Biochemical and Biophysical Communications. (2004) 318:311-316.


TPM® – Mechanisms of Action

TPM® utilizes two primary mechanisms of action to deliver compounds into or through the skin. Both mechanisms rely upon the structure of TPM® and the way in which it interacts with lipids and membranes in the skin, to safely and effectively deliver the active molecule. Our formulators make a deliberate decision on which mechanism of action to apply, depending on the preferred route of administration for the specific molecule under development.

Click here to watch our TPM® Mechanism of Action video

  • Vesicular Delivery - TPM® Mechanism of Action
  • Vesicular Delivery - TPM® Mechanism of Action

TP and T2P (TPM® ) can self-assemble into highly deformable nanoparticles (vesicles) to encapsulate active ingredients, increasing their absorption into the skin or through the dermal layers into systemic circulation. The simplest TPM® vesicles consist of TPM®, a co-solvent, and water. TPM® vesicles are easy to manufacture using Phosphagenics’ patented process and have the following characteristics:

  • Ultra-deformable and able to increase dermal absorption
  • Range in size from approximately 50-500 nanometers
  • Entrap high percentages of APIs
  • Lipid Packing Disturbance - TPM® Mechanism of Action
  • Lipid Packing Disturbance - TPM® Mechanism of Action
  • Lipid Packing Disturbance - TPM® Mechanism of Action

Tightly packed ceramide, fatty acids and cholesterol form the ‘mortar’ of the strata corneum, the primary barrier of the skin. Like most penetration enhancers, TPM® alters the packing of lipids, decreasing the barrier quality of the ‘mortar’ within the strata corneum to allow increased passage of co-formulated active ingredients.

Cryo-TEM (cryo-transmission electron microscopy) images were obtained from formulations with differing ratios of tocopherol phosphate (TP) to phosphatidylcholine (PC), a standard membrane forming phospholipid. While 100% PC forms standard liposomes, 100% TP forms small, micelle like structures; the addition of 25% TP to 75% PC disturbs packing of PC, transforming liposomes into long sheets of membrane.