Does cream get absorbed into the bloodstream? A look at topical vs. transdermal delivery

October 10, 2025 •

5 min read

The human skin, our body's largest organ, is a highly effective protective barrier designed to keep external substances out. However, a common misconception is that all creams readily absorb into the bloodstream, a process that is far more complex and selective than many believe. This article explores how and when cream ingredients can be absorbed, focusing on the key differences between topical and transdermal formulations and the factors that influence their pharmacological action.

Quick Summary

The skin acts as a selective barrier, allowing some cream ingredients to penetrate but rarely reaching the bloodstream for systemic effects, unless specifically engineered to do so. Dermal absorption is influenced by the cream's formulation, molecule size, and the skin's condition. Transdermal products are designed for systemic absorption, while topical ones remain localized. Overuse or applying to compromised skin increases absorption risks.

Key Points

Skin is a barrier: Your skin's outermost layer, the stratum corneum, is a strong protective barrier that prevents most substances from entering the bloodstream.
Topical vs. Transdermal: The key difference lies in purpose; topical creams treat localized areas with minimal absorption, while transdermal creams are specifically formulated for systemic absorption.
Absorption factors: Several elements, including molecule size, skin condition (e.g., compromised skin allows more absorption), application area, and cream formulation, influence the amount of a substance that enters the bloodstream.
Engineered for absorption: Transdermal creams contain special ingredients called penetration enhancers to help active compounds bypass the skin's barrier and reach the blood vessels.
Overuse risks: Even with creams designed for localized use, applying large quantities or using them on damaged skin can increase systemic absorption and raise the risk of adverse side effects.
Molecular size matters: Smaller, lipid-soluble molecules in creams and cosmetic products are more likely to penetrate the skin's layers than larger molecules, though absorption is still limited for most skincare.

The Skin: A Smart Barrier Against Systemic Absorption

At its most fundamental level, your skin is a protective fortress. The outermost layer, the stratum corneum, is a dense, lipid-rich barrier of dead skin cells that effectively blocks most foreign substances. The idea that a significant portion of everything applied to the skin enters the bloodstream is a myth; if this were true, our body’s largest organ would be a major liability. For a substance to be absorbed into the bloodstream, it must navigate this complex, multilayered defense system to reach the vascularized dermis layer below. This is not an easy feat and depends on several critical factors, including the molecule's properties and the cream's formulation.

How Cream Ingredients Navigate the Skin Barrier

For a cream to have a systemic effect, its active ingredients must pass through several layers of skin. The process primarily occurs via passive diffusion, a mechanism where molecules move from an area of high concentration (the cream) to an area of lower concentration (the deeper skin layers and blood vessels).

Routes of entry include:

Intercellular Route: This is the primary pathway for most ingredients. They travel through the narrow, lipid-filled spaces between the corneocytes (the dead cells of the stratum corneum). This route is more accessible for small, fat-soluble (lipophilic) molecules.
Transcellular Route: Less common, this path requires molecules to pass directly through the cells themselves. This is only possible for very specific, small molecules.
Appendageal Route: This minor pathway involves ingredients entering through the skin's appendages, such as hair follicles and sweat glands. These routes are less significant for overall systemic absorption due to their small surface area but can be important for some formulations.

Topical vs. Transdermal: The Key Distinction

The most important distinction to understand is the difference in intent between topical and transdermal creams. These are not just different names for the same product; they are designed for fundamentally different purposes.

Topical Creams: Designed for Localized Action

Topical creams are engineered to stay on or within the outer layers of the skin (the epidermis) to treat a local condition.

Purpose: To treat skin conditions like rashes, inflammation, infections (e.g., fungal cream), or acne directly at the site of application.
Absorption Profile: Minimally absorbed systemically. Their active ingredients are typically larger molecules or are formulated to work on the surface, preventing significant amounts from reaching the bloodstream.

Transdermal Creams: Engineered for Systemic Delivery

Transdermal creams, along with patches, are specifically designed to be absorbed through the skin and into the systemic circulation to have a therapeutic effect throughout the body.

Purpose: To deliver medicine systemically, such as for pain management (e.g., compounded pain creams), hormone replacement therapy, or nicotine replacement.
Absorption Profile: Intentionally formulated with penetration enhancers to facilitate the movement of active ingredients through the skin barrier to the blood vessels in the dermis.

Factors That Influence Dermal Absorption

Several factors determine how much of a cream's active ingredient will be absorbed into the bloodstream. These include:

Molecule Size and Polarity: Smaller molecules are more likely to pass through the skin barrier. Lipophilic (fat-soluble) molecules pass more easily than hydrophilic (water-soluble) ones, as the outermost skin layer is fat-loving.
Skin Condition: Compromised or damaged skin, such as from cuts, burns, or conditions like dermatitis, has a weakened barrier. This significantly increases permeability and the potential for systemic absorption. Thinner skin areas like the face, armpits, and genitalia are also more permeable.
Application Method: Applying a cream over a large surface area or using an occlusive dressing (like a bandage) can significantly increase the total absorbed amount. Factors like skin hydration and temperature also play a role; warmer, more hydrated skin absorbs more effectively.
Formulation: The cream's vehicle or base (e.g., ointment, gel) and any included penetration enhancers dramatically influence absorption. Ingredients like certain fatty acids or alcohols are added to increase permeability.

Comparison Table: Topical vs. Transdermal Creams


Feature	Topical Creams	Transdermal Creams
Intended Effect	Localized to a specific area of the skin.	Systemic (whole-body) effect via bloodstream.
Target Location	Epidermis (outer layers of skin).	Blood vessels in the dermis and beyond.
Molecular Design	Larger molecules or designed to stay localized.	Smaller, lipophilic molecules for easier passage.
Absorption Goal	Minimal systemic absorption.	Significant and controlled systemic absorption.
Example	Hydrocortisone cream for a rash.	Compounded pain cream or nitroglycerin cream.
Formulation	Designed to work on the surface, often containing barrier-forming ingredients.	Includes specific penetration enhancers to cross the skin barrier.

Systemic Absorption Risks and Considerations

While most skincare products are harmlessly absorbed only into the superficial layers, an intentional systemic effect from a transdermal cream also comes with potential risks. These risks are why these products are carefully regulated and prescribed by healthcare professionals. Overuse or improper application can lead to adverse effects.

For example, excessive or long-term use of potent topical corticosteroids on large areas of the body, particularly on damaged skin, can lead to adrenal suppression and other systemic side effects, as enough of the steroid can be absorbed to disrupt the body's natural hormone balance. Similarly, powerful compounded pain creams or anesthetic creams (containing lidocaine or prilocaine) applied excessively can lead to toxic blood concentrations, causing central nervous system or cardiovascular complications.

For consumers, the most common unintended absorption risk comes from certain chemical sunscreen ingredients, such as avobenzone and oxybenzone, which have been detected in the bloodstream after use. While the health implications are still under study, this has prompted a closer look at these ingredients by regulatory bodies like the FDA.

Conclusion

In conclusion, the idea that every cream you apply is a direct route to your bloodstream is a simplification of a very complex process. The skin is an excellent barrier, and whether a cream’s ingredients reach your bloodstream depends heavily on the product's design. Topical creams are engineered for localized effects and minimal systemic absorption, while transdermal formulations are specifically created to facilitate entry into the blood. Factors like molecular size, skin integrity, and application techniques all play a crucial role in the degree of absorption. Understanding this distinction is vital for proper medication use and for making informed decisions about the products we apply to our bodies. As with any medication, it is important to follow a healthcare professional's guidance when using transdermal products and to report any unusual side effects.

Useful Resources

Frequently Asked Questions

Most cosmetic and skincare creams are designed to work on the skin's surface and upper layers. While some very small molecules can penetrate the skin, significant absorption into the bloodstream from standard skincare products is rare and minimal due to the skin's protective barrier.

Penetration refers to a substance entering the outer layers of the skin (the epidermis). Absorption means the substance has moved deeper, through the skin's layers, and entered the bloodstream for systemic circulation.

Factors that increase systemic absorption include applying the cream to large areas of the body, using it on compromised or broken skin (like cuts or burns), covering the area with a bandage, and using a formulation that contains penetration enhancers.

Yes. These are known as transdermal creams and are specifically formulated to deliver medication through the skin and into the bloodstream. Examples include certain compounded pain creams and older formulations of nitroglycerin cream.

Yes, especially with powerful medicinal creams. For instance, overuse of potent topical steroids can lead to systemic side effects like adrenal suppression. Similarly, excessive use of creams with anesthetic agents like lidocaine can lead to toxic blood levels.

Skin thickness plays a major role in absorption. Thinner areas of the body, such as the face, neck, and genital regions, are much more permeable and allow for greater absorption compared to thicker skin on the palms and soles of the feet.

Yes, the appendageal route, which includes hair follicles and sweat glands, is a pathway for skin absorption. While it's a less significant route for overall systemic absorption compared to diffusion through the stratum corneum, it can be important for some formulations.