Ultrasonic Preparation of Liposomes for the Pharmaceutical and Cosmetic Industry

By AZoNano Staff Writers

Table of Contents

Ultrasonic Liposomes Formation
Ultrasonic Encapsulation of Agents into Liposomes
Liposomal Emulsions
Liposomal Dispersions
About Hielscher Ultrasonics


Microscopic vesicles such as niosomes (synthetic vesicles), liposomes (liposome-lipid based vesicles), ethosomes (ultradeformable vesicles with high alcohol content), and transferosomes (ultradeformable liposomes) can be synthetically prepared to act as globular carriers into which active molecules can be embedded.

These vesicles, ranging in diameter from 25 to 5000nm, have become popular topical drug carriers in the cosmetic and pharmaceutical industry, such as immunization, drug delivery, and genetherapy. Ultrasound is a well-known technique for liposome preparation and for encapsulation of active agents into these vesicles.


Liposomes are oligolamellar, unilamellar, or multilamellar vesicular systems, made of the same type of lipid bilayer that makes up cell membrane. They are used as biocompatible carriers of proteins, peptides, drugs, plasmic DNA, ribozymes, or antisense oligonucleotides for cosmetic, pharmaceutical, and biochemical purposes.

Vesicles are differentiated based on their size and composition - there are multi-lamellar vesicles (MLV) 0.1-10µm in diameter, and unilamellar vesicles, which are further categorized into giant unilamellar vesicles (GUV, >1 µm) vesicles, large unilamellar vesicles (LUV, 100-500 nm), and small unilamellar vesicles (SUV, <100 nm).

The versatility in physical parameters and in particle size of the lipid vesicles presents an attractive potential for customizing them for different applications.

Figure 1. Chemical structure of hydrogenated phosphatidylcholine

Phospholipids, which make up the composite structure of liposomes, include a hydrophilic head group and a long-chain hydrocarbon tail group, which is hydrophobic. The liposome membrane can be easily integrated into the human skin, since their phospholipid composition is similar to that of the skin barrier.

When the liposomes fuse with the skin, they deliver the encapsulated agents directly to the target, where the actives can function effectively. Therefore, the liposomes enhance skin permeability and penetrability for the cosmetical and pharmaceutical agents.

The vacant vesicles, without encapsulated actives, are also therapeutic for the skin, since the phosphatidylcholin includes two essential compounds, choline and linoleic acid, which the human body cannot produce.

Ultrasonic Liposomes Formation

Liposomes can be generated using ultrasonics. Amphiphilic molecules based on biological membrane lipids are the basic materials for liposome preparation.

Figure 2. VialTweeter

For the formation of SUVs, the lipid dispersion is gently sonicated in an ice bath, with an instrument like the VialTweeter (Figure 2), the UP50H handheld ultrasonic device (Figure 3), or the UTR200 ultrasonic reactor (Figure 4).

Figure 3. Handheld ultrasonic device UP50H

The duration of this ultrasonic treatment is approximately 5 to 15 minutes. Another technique to create SUVs is the sonication of multi-lamellar lipid vesicles.

Hielscher Ultrasonics supplies a wide range of sonotrodes, ultrasonic devices, and accessories, allowing users to select a sonicator with capabilities most suited to their needs.

Figure 4. Ultrasonic reactor UTR200

Ultrasonic Encapsulation of Agents into Liposomes

Ultrasound processing is a suitable tool for preparing and forming liposomes for the dermal delivery of active agents. Prior to encapsulation, the liposomes form clusters because of the surface charge-charge interaction of phospholipid polar heads (Míckova et al.
2008, Acta Veterianaria Brunensis); these clusters need to be broken up for effective encapsulation.

For example, Zhu et al. (2003, Chinese Chemicals Letters) illustrates the encapsulation of biotin powder in liposomes by ultrasonication. As the biotin powder was introduced into the vesicle suspension solution, the solution was sonicated for about 1 hour. Following this treatment, biotin was found to be encapsulated in the liposomes.

Liposomal Emulsions

In order to improve the nurturing effect of cosmeceutical formulations such as anti-aging or moisturizing lotions, creams, gels etc., emulsifiers are added to the liposomal dispersions to stabilize large amounts of lipids.

However, the addition of emulsifiers normally restricts the capability of liposomes and weakens the barrier affinity of phosphatidylcholine. Nanoparticles made of lipids and phosphatidylcholine, provide a suitable solution to this problem.

These nanoparticles are formed by an oil droplet enclosed by a single layer of phosphatidylcholine. The use of nanoparticles enables formulations that absorb more lipids and yet remain stable, so that additional emulsifiers are not required.

Ultrasonication is a well-established technique for producing nanodispersions and nanoemulsions. Highly intensive ultrasound provides the power required to disperse a liquid phase i.e. dispersed phase in small droplets in a second phase. Emulsifiers and stabilizers are added to the emulsion so as to stabilize the newly formed droplets of the disperse phase against coalescence.

Liposomal Dispersions

Liposomal dispersions based on unsaturated phosphatidylcholine lack oxidation stability - this can be improved by adding antioxidants, such as vitamins C and E.

Ortan et al. (2002) achieved good results in their study of ultrasonic preparation of Anaethum graveolens liposomes. The stability measurements, based on size distribution and essential oil loss, demonstrated that the content of volatile oil is maintained by liposomal dispersions. This indicates that the entrapment of the essential oil in liposomes improved the oil stability.

Figure 5. Size distribution of MLV dispersions, for L year

Figure 6. Size distribution of SUV dispersions for 1 year


Ultrasound is a well-known technique for liposome preparation for the pharmaceutical and cosmetic industry. Hielscher ultrasonic processors are suitable for using in these industries. In addition to high efficiency in the continuous emulsification, the ultrasonic devices are easy to operate and maintain.

Moreover, the ultrasonic power can be adapted to suit specific products and emulsification needs. Special flow cell reactors to meet advanced clean-in-place (CIP) and sterilize-in-place (SIP) requirements are also available.

About Hielscher Ultrasonics

Hielscher Ultrasonics is a family business, located in Teltow near Berlin (Germany). The main emphasis of its activities is the conception, development and production of ultrasonic devices for the use in laboratory and industrial applications. Technological innovations together with the realization of new ultrasound based processes substantiated the company growth and its market acceptance.

Today, ultrasonic devices made by Hielscher Ultrasonics are being used in laboratories and production plants on all continents across the world. More than 70% of the total sales is based on export. Almost every second device is supplied to customers outside Europe. Hielscher Ultrasonics integrates the ultrasonic devices into complex ultrasonic systems, such as wire cleaning systems, too. The systems are produced to meet the customers requirements in terms of power, extended range of accessories and steady state proof equipment.

This information has been sourced, reviewed and adapted from materials provided by Hielscher Ultrasonics GmbH.

For more information on this source, please visit Hielscher Ultrasonics GmbH.

Date Added: Feb 17, 2014 | Updated: Feb 20, 2014
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