Liposomes for Transdermal Drug Delivery

Introduction

Transdermal administration has many advantages over traditional oral or intravenous administration, such as avoidance of the first-pass effect in the liver, stable blood levels, and long maintenance of the drug effect. However, the barrier effect of the cutaneous stratum corneum is a serious obstacle to the transdermal absorption of many drugs. The use of liposome delivery has effectively improved this situation and is widely used.

Advantages

• Targeting the skin tissue and increasing the concentration of the drug locally in the skin.
• Forms a drug reservoir in the epidermis and dermis with long-lasting and slow-release effects.
• Reducing adverse reactions.
• Reduced drug irritation.
• The hydrated phospholipids of liposomes promote skin hydration and have a protective effect on the skin.

Mechanism

The mechanism of action of liposomes as a transdermal drug delivery vehicle is still unclear, but based on research findings, the various mechanisms by which liposomes facilitate drug penetration into the skin are summarised below.

• Free drug mechanism

After the liposomes release the drug at the surface of the skin, the drug particles penetrate the skin without interruption.

• Hydration mechanism

The transdermal absorption of liposomes may alter the structure of the keratinocyte interrogation by increasing the wetting and hydration of the stratum corneum, facilitating the entry of the drug into the intercellular matrix by diffusion and other effects.

• Integration mechanism

The fusion of phospholipids with the epidermal lipid layer changes its composition and structure, which forms a flat granular structure that reverses the barrier effect and allows drug-encapsulated liposomes to pass through the interstices of these lipid particles.

• Penetration of intact vesicles into or through the SC

Special lipid carriers can penetrate through intact skin, probably due to the difference in water concentration between the surface and the interior of the skin producing an osmotic pressure gradient and hydration energy, which provides the power source for the lipid carriers to penetrate the skin.

• Hair follicle penetration

It has also been found that liposomes can also penetrate the skin along the follicular pathways of the epidermis, but this effect is generally weak.

Fig. 1 Various mechanisms by which liposomes can facilitate drug delivery to the skin (Ashtikar M, 2016)

Classifications

Liposomal transdermal drug delivery is generally divided into two main categories according to the purpose of administration: systemic therapeutic effects through transdermal absorption into the bloodstream and local therapeutic effects through the facilitated penetration of liposomes into the skin. In addition to the traditional liposomes, several novel liposomal carriers for transdermal drug delivery have been derived through changes in the type and proportion of liposomal membrane materials to meet a variety of therapeutic needs.

1. Ethosome. A higher concentration of ethanol is used instead of cholesterol in traditional liposomes to obtain lipid vesicles with good permeability and encapsulation rate. Compared to conventional liposomes, this formulation is characterized by a high encapsulation rate, good deformability and fluidity, low skin irritation, and good transdermal effect, which allows it to pass through the stratum corneum more effectively.
2. Ransfersomes. Liposomes constructed using phospholipids and surfactants are called transfer bodies, which are highly deformable and highly hydrophilic. The transmitter increases the transdermal efficiency and retention of the drug in the skin.
3. Non-ionic surfactant vehicle, Niosomes. It is constructed using a non-ionic surfactant, which offers better chemical stability, skin penetration, and lower cost.
4. Proliposome. It is prepared from non-ionic surfactants and phospholipids, and sweat allows it to act as a liposome. It overcomes the disadvantage of the instability of liposomes.
5. Others. In addition, new types of liposomes constructed with various modifications on the surface of the liposome or with the addition of some other components can also increase skin permeability. These include flexible liposomes, elastomeric liposomes, skin keratin-like liposomes, and other liposome-like dosage forms.

About BOC Sciences

We can design a variety of liposome products containing the most complex compounds. Our scientists can customize liposomes (any size and concentration) to meet your different needs. We have the ability to perform the entire program from liposome design to PK modeling.

Reference

1. Ashtikar M; et al. Transdermal delivery from liposomal formulations - Evolution of the technology over the last three decades. J Control Release. 2016 Nov 28; 242: 126-140.