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G. Blume*

Liposomes = Liposomes ?
Keywords: Liposome, Drug Carrier System, Penetration

somes (ceramides), sphingosomes


(sphingolipids), nanosomes (phospho-
lipids), nio- somes (non-ionic surfac-
tants) and ???-somes. All of them are
»fatty bodies« that show individual
Zusammenfassung 1. What are liposomes? characteristics due to their different
lipids.

Liposomen sind mikroskopisch kleine Liposomes are microscopic small vesi-


Vesikel (Hohlkugeln), bestehend aus cles (hollow spheres), consisting of one
einer oder mehreren Lipiddoppelschich- or several lipid bilayers that surround
ten, die sich um einen wässerigen Kern a watery nucleus. They are used in the
lagern. Sie werden in der Kosmetik als cosmetics as carrier systems and as sta- 2. Penetration of liposomes
Tra nsportsysteme, zur Stabi I isierung von bi lizer of active substances and regard' (Dr. U. Schäfer, University of
Wirkstoffen oder aufgrund ihrer feuch- ing their moisturizing properties as Saarbrücken)
tigkeitsspendenden Eigenschaften ein- well(Fig. 1).
gesetzt.
Der Begriff »Liposome« kommt aus ln this article you will only be informed
dem griechischen und bedeutet »Fett- about liposomes made of lecithin. Not
Körperchen«. Und damit fängt die Ver- only the excellent moisturizing effects
wirrung an. Welches »Fett« bildet den of this kind of liposomeswill be report-
Bestandteil der Liposome? lm allge- ed but advertisements also more and
meinen werden Liposomen aus Leci- more claim their properties as carrier
thin hergestellt, zumindest bestand system:
das erste in der Literatur beschriebene
Liposome aus Phospholipiden (A.D. Fig. 1 Liposome - »Liposomes are microscopic small
Bangham;Adv. Lipid Res., 65-1 04, 1 963). hollow spheres filled with active in-
Lecithin selber ist aber schon ein Ge- gredients. They are able to pene-
misch aus ganz verschiedenen Phos- The byword »liposome« has it's origin trate into deeper skin layers«.
pholipiden, die sich in den Kopfgrup- from the Greek and means »fatty - »Owing totheirsmall size, theyfind
pen oder in den Fettsäureketten un- body" - and here the confusion begins: their way into these skin layers in
terscheiden können. Which fat is component of the lipo- which the important processes of
Aber dem nicht genug. Zu den Liposo- somes? Liposomes are generally made the regeneration take place«.
men zählen noch die Cerasome (Cera- of lecithin, at least the liposomes de- - »Liposomes have the unique capac-
mide), Sphingosome (Sphingolipide), scribed firstly in the literature consist- ity of transporting active ingredients.
Nanosome (Phospholipide), Niosome ed of phoshpolipids (A.D. Bangham; They are in a position to transport
(non-ionic surfactants) und ???-some. Adv. Lipid Res.,65-104, 1963). However; deeply into the epidermis«.
Alles »Fett-Körperchen«, die wegen ih- lecithin for itself is a blend of quite dif-
rer verschiedenen Lipide unterschied- ferent phospholipids that can be dis- - »The pure vegetable liposomes pro-
duced of soy-lecithin penetrate par-
liche Eigenschaften aufweisen. tinguished in its head groups and its ticularly deep into the skin due to
fatty acid chains (Fig. 2). their structure similar to the skin.
Howevel that's not all! Beside the There they develop their skin
Artikel liegt in Deutsch vor. group of lipsomes there are also cera- smoothing effects«.
itte wenden Sie sich an den Verlag.
- »Liposomes are used as a carrier of
active substances. They go through
the skin and release their contents
in the deeper skin layers of the
upper skin, thus they not only act on
the surface«.
fatty acids head group (here: choline) - »The liposomal encapsulation en-
ables the active substances to pen-
etrate through the horny layer and
Fig.2 Phosphilipids to develop their effects there«.

14 SÖFW-Journ al, 126. Jahrgang 1 1-2000


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- »Liposomes = lipid-like micro vesi- The decisive difference between these Franz-type diffusion cells. One made
cles that penetrate as carrier for ac- variable liposomes was the lecithin sure that the acceptor compartment
tive substances into the upper skin, used for this purpose. Rovisomes con- was filled with phosphate buffer below
that spread out there and then en- sist of a high-quality phospholipid the skin to avoid over-hydration (IJ.
able the distribution of the active with a percentage of 80 % phosphat- Franz, Curr. Probl. Dermatol. 7, 58-68,
substances up to the deepness of idylcholine. The fatty acids of these 1978). Three hours after application,
the epidermis«. phospholipids are mainly unsaturated the skin surface was cleaned and skin
(linoleic acid) and provide the lipo- cylinders were punched. After cryo-fix-
Have all liposomes the characteristic to some with a flexible membrane. Fur- ation, pieces with a thickness of 10 pm
deliver active substances into the deep- thermore, liposomes were produced were cut. The penetration of the mark-
er skin layers? How must a liposome of a very »cheap« lecithin with a small er-molecules were examined by confo-
look like to fulfilthese claims actually? amount of phosphatidylcholine, which cal laser scanning microscopy (Fig. 3).
To answer these questions, one inves- have, however, the feature of unsatu- Only the Rovisomes act as a carrier
tigated the liposomes' ability to pene- rated fatty acids. The PL 9OH-lipo- system that sets free the lipophilic as
trate in dependency of the lecithin somes are based on a very high con- well as the hydrophilic marker in the
composition. tent of phosphatidylcholine (< 90 %) epidermis, so that the dyes even can be
For this, two different f luorescently la- with hydrated, saturated fatty acids detected in the dermis. ln contrast, the
belled molecules -the hydrophilic car- that strengths the vesicle membrane. PL 9OH-liposomes with the rigid lipid
boxy-f luorescein and the lipophilic rhod- The ethanolic solution and the three membrane keep the fluorescent dye
amin-PE - have been encapsulated into liposome-preparations were non-oc- fixed on the skin surface. Other re-
liposomes with the same size, the same clusively and ex vivo applied onto hu- search groups describe the ability of
loading and the same quantity of leci- man skin obtained after cosmetic sur- flexible and fluid liposomes to trans-
thin. gery. The experiment was carried out in port the active ingredients increased

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5ilab
SÖFW-Journ al, 126. Jahrgang 11 -2000 15
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finished formulations (C. Johann und


Ethanol ROVISOME Pl2$Liposone Pl90E-Liposome G. Blume, GIT Labor-Fachzeitschrift
(special magazine for laboratory pur-

ffi
poses) 4, 360-352, 1999).
ln this technique, the sample is trans-
ported in a liquid flow from the injec-

II II II II
tor to the detector and is separated.
^ffi:*W
trffifii:,#, The separation is caused through the
interactions with a field vertical to the
hydmphific
transport direction. The nearer a par-
Caöoxy- ticle stays on the accumulation-wall
fluorescein (big vesicles), the slower it is transport-
ed in the parabolic flow-profile, ac-
cordingly it elutes later (small particles
arrive at first) (Fig. 4).
lipophilic
Ten percent of liposomes were stirred
P.hodamin+E into OAI/ cremes (MN-03-1 198-560*),
and the particle size of the vesicles was
measured immediately after this pro-
cedure and after a three-months stor-
age at room temperature. ln this ex-
periment one also compared three li-
posome preparations with each other
Fig. 3 Penetration of different liposomes (Rovisome, PL 90H-liposomes and PL 25-
liposomes).
The very stable and rigid PL 9OH-lipo-
somes keep a constantly vesicle-size in
into the skin compared with vesicles shown that these carrier system is par- the finished formulation over time.
that are available in the crystalline ticularly suitable for the transport of The Rovisomes'size on the other hand
phase (M. Kirjavainen et al., J Control hydrophilic active ingredients. Despite (+ 70 pm) grow a little bit due to an in-
Rel. 58, 207-214, 1999; B.A.l. van den of the fluid membrane, the transmis- crease of the water envelope bound
Bergh et al., lnt. J. Pharm. 167,57-67, sion-efficiency of about 80 % for water- on the membrane-surface. This hydro-
1998). Furthermore, owing to the high soluble drugs can be achieved (G. Blume philic surface delays the penetration
amount of ethanol (that increases the et al., SOFW Journal 5, 298-301, 1997). of the Rovisomes from such a finished
penetration), the marker-solutions formulation into the skin in compari-
could colour the stratum corneum. Li-
posomes produced ofthe »cheap« lec- 3. The stability of Iiposomes
ithin with a low content of phosphat-
idylcholine do not show any penetra- in finished formulations
tion-properties !
(Dr. C. Johann, Wyatt GmbH,
Noticeable during the literature-inves- Woldert) * Formulation (lNCl-Declaration): Water, Hy-
tigations was that for penetration drogenated lojoba Oil, Steareth-2, Glycerin,
studies with Iiposomes nearly only lipo- PPG1 5 Stearyl Ether, Hydrogenated Canola Oil,
philic markers are used that are firmly The AFFF (asymmetrical flow-field- Dioctyl Adi- pate, Steareth-2l, Dicaprylyl Ether,
Alcohol, Shea Butter, Lecithin, Cyclomethicone,
tied into the vesicle membrane. On fractionation) is a new technique that Polyacrylamide, Cl 3-14 lso-paraffin, Laureth-7,
studies with Rovisomes it could be enables the detection of liposomes in Xanthan Gum, Sodium Hyaluronate, Preserva-
tives

Field

TTTTT c

G:==- og?e liPommcs


ü
s

Tffi
+; owe ;
6

E
c
o
U

,r\
t,,\ o o

t\,'
L
time

Fig. 5 Size distribution of different liposomes in a final for-


Fig. 4 Principle of AFFF mulation

16 SÖFW-Journ al, 126. Jahrgang 11 -2000


CosnETrcs

son with the application of a aqueous


Iiposome-dispersion (G. Blume et al.,
SOFW Journal 5, 298-301, 1997). The
»cheap« liposomes cannot be detect-
ed in the finished formulation defi- 80
nitely. Particles bigger than 400 pm in
diameter are found to lie in the area of s
fat drops. A similar result is obtainable 60
from finished formulations without =
additives of liposomes (Fig. 5). EIE
@ 40

-A- Rovisome Retinol


4. Stability of Retinol in 20 -O- Nanoparts Retinol

liposomes -I - strbili*"d Re.tinol


-V- O^^/Creme + Rovisome Retinol
(D.D. Verma and Prof. A Fahr 0
University of Marburg)

In this experiment the chemical stabil- Fig. 6 Stability of Retinol encapsulated or in its free form
ity of pure retinol and two »liposo-
mal« encapsulations with the same lip-
id composition was compared with
help of reversed-phase HPLC (Methode proven that these »cheap-liposomes« duction of wrinkles (G. Blume und E.
nach D.D. Verma, Universität Marburg). do not show any vesicle-stability and Teichmüller, Cosmetics and Toiletries
Retinol was directly integrated into that they are unsuitable to carry active Manufacture Worlwide, 1 35-1 39, 1 997).
the lipid membrane - on the one hand substances into the skin. Consequent- Conclusion: The subject »lipsosomes«
encapsulated into Rovisomes, on the ly, they do not correspond to their includes several »lipid-bodies« with
other hand it was incorporated into claims as »liposome-containing formu- the same lNCl-declaration, that, how-
vesicles that - in contrast to the Rovi- lations« respectively »liposomes that ever; differ significantly in price, in
somes - contained the vitamin solved are capable to penetrate, and that en- quality and in their properties. There-
in oil (e.9. nanoparticles, nanosomes able the transport of active substanc- fore, they should be investigated
respectively nanospheres). Rovisome es into the skin«. strictly with regard to ability and mar-
Retinol was also incorporated into a Lipid vesicles, produced of the high- keting claims.
O/C-creme (*MN-03-1198-550) and quality PL 90 H (hydrogenated leci-
checked on the stability of the finished thin) show an excellent stability in the Liposomes = Liposomes ?
formulation (Fig. 5). finished formulation and have the No!
ln this example it becomes clear that ability to stabilize active ingredients.
not only the lecithin composition is de- Liposomes with a rigid membrane on
cisive but also the kind of the encapsu- the other hand, transport the encap-
Iation. lndeed one can encapsulate a sulated substances not into the epider-
higher concentration of lipophilic ac- mis but fix the lipids as well as the ac- *Author's address:
tive ingredients into the nanoparts, tive ingredients on the skin's surface Dr. Gabriele Blume
howevel due to the »half« bilayer, the and there, they act as a moisturizer. c/o ROVI GmbH
membrane becomes unstable and, as a Special designed liposomes, such as Breitwiesenstrasse 1
will be de-
result of this, the retinol Rovisomes, have the characteristic to D-36381 Schlüchtern
graded faster. stabilize the integrated active sub-
The incorporation of Rovisome Retinol stances in the vesicle dispersions and in
into this OAly'-creme leads to a further
slight increase of stability of the vita-
the finished formulations as well.
These liposomes also show a high
A
mins in the formulation. The stability stability in finished formulations and
of the retinol in the nanoparts on the are able to carry the active ingredients
other hand could not be increased by out of the formulation into the deep-
incorporating them into the cream. er skin layers (G. Blume etal., Euro Cos-
metics 3, 30-32, 2000). ln addition to
this, Rovisomes are capable to smooth
the skin and to cause a significantly re-

4. Conclusion

The lNCl declaration of the so-called


»cheap-liposomes« and the Rovisomes
is identical and called »lecithin«. How-
eveq in investigations it was clearly

5ÖFW-Journ al, 126. Jahrgang 1 1 -2000 17