Alguien sabe algo de liposomas??

[mimoko]

que interesante..

tengo un cutreultrasonidos (de limpiar la ferula dental)...tengo que hacer el experimento

[labenplantada]

Ya tardas, hija .

Es mejor limpiar la férula con ultrasonidos? No sabía . Cuéntame porque yo limpio la mía con cepillito y jabón.

Has comprado los cutreultrasonidos por internet o lo venden en tiendas tipo Corte Inglés?

[mimoko]

lo tenia de antes de la férula, pero para la férula va bien.Es que la mia tiene mogollon de recovecos y solo se limpiaba bien con mucho curro y pastillas.
No obstante, le doy con cepillico cuando me la quito, antes de echarla al cacharro, de tanto en cuanto con pastillas

el cutreultrasonidos me lo regalo alguien , ahora no recuerdo quien....mi madre? mi suegra? me lo regalaron en su dia, para limpiar joyitas.
Siempre me quejaba de haberme desprendido de mi ultrasonidos al desmontar el taller en madrid, que lo echaba en falta . este no es como uno profesional ni de blas, pero algo si quita...
es cutre cutre, eh? no creo que sea ni del cortinglés...mas bien del cortechino

ais, ya tardo si...pero tardaré.Tengo un montón de deberes que hacer estos dias,ahora que se nos han ido los invitados...y me he propuesto no enredarme con experimentos...
claro que las propuestas son solo eso, propuestas

edito....tengo que meter un recipiente dentro del ultrasonidos lleno de agua muy caliente pero no hirviendo...
eso es un problema, mi cutreultrasonidos es pequeño...tendria que hacerme con un matraz chiquitico..
se me ocurre que quizas en un vasito de chupito...
lo que no se es si será masa de agua suficiente como para mantener la temperatura...
ais no se...ya em pongo a maquinar con esto y tengo que hacer la comida! ale, al tajo!

[magoo68]

Ya veo otro experimento en marcha, je, je. Mimoko, en el hilo habla de usar una bolsa plástica.

Labemplantada, qué lecitina estás usando, de soya o de huevo?

[labenplantada]

De soya. por qué?

[magoo68]

Supuestamente la de huevo tiene más fosfatidilcolina que la de soya. Quería saber si usabas la de huevo y si notabas alguna diferencia.

Esta es difícil de conseguir por estos lados, sólo en cápsulas con otros aditivos. Al final la encargué en Taiwan, 99% pura en polvo. Por cierto que el suplidor tiene otras cosas interesantes, un tipo de vitamina C que no conocía, AA2G Ascorbic Acid 2- Glucoside, ácido láctico en polvo al 99%, kinetina pura, ácido férulico grado cosmético 98% pureza, $10.95 la onza (me encantó el precio), crisina, otros péptidos, vitaminas y varios activos.

[Azimut]

Yo tengo un ultrasonidos (de limpiar joyitas y relojes...) del Lidl y me va bien. A ver si me animo a hacer algún experimento.

[labenplantada]

Supuestamente la de huevo tiene más fosfatidilcolina que la de soya. Quería saber si usabas la de huevo y si notabas alguna diferencia.

Y qué pasaría si lo hacemos con fosfatidilcolina pura? Es lo que tomo para estudiar .

Esta es difícil de conseguir por estos lados, sólo en cápsulas con otros aditivos. Al final la encargué en Taiwan, 99% pura en polvo. Por cierto que el suplidor tiene otras cosas interesantes, un tipo de vitamina C que no conocía, AA2G Ascorbic Acid 2- Glucoside, ácido láctico en polvo al 99%, kinetina pura, ácido férulico grado cosmético 98% pureza, $10.95 la onza (me encantó el precio), crisina, otros péptidos, vitaminas y varios activos.

Te refieres a skinessentialactives.com ? Si es otro proveedor, puedes pasar la dirección, pliiiiiizzz

[mimoko]

Y qué pasaría si lo hacemos con fosfatidilcolina pura? Es lo que tomo para estudiar .

interesantísima reflexion!!!!

[magoo68]

Síiiii, pueden ser muchas posibilidades! Me puse a escarbar entre los libros y encontré información en el Handbook of Cosmetic Science and Technology que habla sobre fosfatidilcolina y liposomas. Aquí la pongo, es largo pero vale la pena saber estas cosas a la hora de formular.

Liposomes
Hans Lautenschla¨ger
Development & Consulting, Pulheim, Germany
INTRODUCTION
Publications about and patents on liposomes, along with their different chemical components,
preparation, and use in skincare products have often been reviewed [1–4]. The
reviews do not need any additional comments. Of interest are general questions, such as
why liposomes should be used in cosmetics, which functionalities are expected from them,
and which advantages they do provide compared with alternative formulations.
The properties of the widely used main component of liposomes, phosphatidylcholine,
play a key role for answering these questions. Other compounds such as niotensides
and ceramides, which are naturally predestinated for the preparation of liposomes, are less
important today. Niotensides do not offer superior claims, and ceramides are not available
in sufficient quantities and qualities at convenient prices.
PHOSPHATIDYLCHOLINE
Looking at the horny layer, which is the barrier against external materials, phospholipids
and phosphatidylcholine in particular play a minor role. The lipid bilayers contain only
traces of phospholipids, and the main components are free fatty acids, cholesterol, triglycerides,
hydrocarbons, and ceramides. But looking deeper into the living part of the
epidermis, phosphatidylcholine is usually found as the most important constituent of all
biological membranes, especially of plasma cell membranes. Over and above that phosphatidylcholine
is the source of phosphocholine to transform ceramides to sphingomyelins.
In this context, phosphatidylcholine stands for living tissues whereas the increase of ceramides
in the cells means that their death by apoptosis is soon ahead (Fig. 1).
Human phosphatidylcholine and phosphatidylcholine of vegetable origin show a
fatty acid composition, which is dominated by unsaturated fatty acids. The fatty acid content
of soy phosphatidylcholine, which is readily available and mostly used in cosmetic
formulas, is characterized by a ratio of linoleic acid up to 70% of the total fatty acids.
Consequently, soy phosphatidylcholine has a very low phase-transition temperature of
below 0C in water-containing systems. This may be the reason for its ability to fluidize
the lipid bilayers of the horny layer, which can be measured by an increase of the transepidermal
water loss (TEWL) after application for a short while. The slight increase of TEWL coincides with the penetration of phosphatidylcholine and active agents, which are coformulated
with phosphatidylcholine. Because of its high content of linoleic acid and penetration
capability, soy phosphatidylcholine delivers linoleic acid very effectively into the
skin, and antiacne properties have been shown as a result [5].
By adhering very strongly to surfaces containing proteins like keratin, phosphatidylcholine
shows conditioning and softening effects, which are known from the beginning
of skincare products’ development. So, e.g., shampoos were formulated in the past very
often with egg yolk to soften hair and prevent it from becoming charged with static electricity.
Egg yolk is very rich in lecithin. The main compound of egg lecithin is phosphatidylcholine.
In a given mixture it is not relevant in which form the phosphatidylcholine is incorporated.
However, when phosphatidylcholine is formulated, it is practically inevitable that
bilayer-containing systems like liposomes will occur, because this is the most natural form
of the material. For example, phosphatidylcholine swollen by water transforms spontaneously
to liposomes when ‘‘disturbed’’ by little amounts of salts or watersoluble organic
compounds, like urea. On the other hand, it has been known for a long time that horny layer
pretreated by phosphatidylcholine can be penetrated much more easily by nonencapsulated
materials. So liposomes are not really needed to turn out the functionalities of phosphatidylcholine,
but they are very convenient because the handling of pure phosphatidylcholine
requires a lot of experience and sometimes patience as well.
Because phosphatidylcholine is known as a penetration enhancer, this property is
usually associated with liposomes. Liposomes are the vesicles said to transport cosmetic
agents better into the horny layer. That is true and, moreover, the conditioning effect
causes the horny layer to become a depot for these agents. Measurements of systemically
active pharmaceuticals revealed that an increase of penetration is not synonymous with
an increase of permeation. Actually, permeation of active agents is often slowed by phosphatidylcholine
in such a way that a high permeation peak in the beginning of the application
is prevented. Instead, a more continuous permeation takes place out of the horny
layer depot into the living part of the body over a longer period of time. This property
makes phosphatidylcholine and liposomes very attractive for the application of vitamins,
provitamins, and other substances influencing the regenerating ability of the living epidermis.
On the other hand, liposomes consisting of unsaturated phosphatidylcholine have
to be used with caution in barrier creams because they do not strengthen the natural barrier
function of the skin with the exception of its indirect effect of supporting the formation
of ceramide I. Ceramide I is known for containing linoleic acid and for being one of the
most important barrier-activating substances. Instead of unsaturated phosphatidylcholine,
a fully hydrogenated phosphatidylcholine (Fig. 2) should be selected for products designed
for skin protection.
Hydrogenated phosphatidylcholine stabilizes the normal TEWL similarly to ceramides
when the horny layer is attacked by hydrophilic or lipophilic chemicals [6]. Table 1
shows a summary of the properties of unsaturated and hydrogenated phosphatidylcholine.
Hydrogenated phosphatidylcholine is synonymous with hydrogenated soy phosphatidylcholine,
which contains mainly stearic and palmitic acid, and semisynthetic compounds
like dipalmitoylphosphatidylcholine (DPPC) and distearoylphosphatidylcholine (DSPC).
Because of their special properties it can make sense to combine unsaturated with saturated
phosphatidylcholine in one and the same cosmetic or dermatological product.

LIPOSOMES
Liposomes are spherical vesicles whose membranes consist of one (unilamellar) or more
(oligolamellar, multilamellar) bilayers of phosphatidylcholine. Sometimes, especially in
patents, reference is made not about liposomes but about ‘‘vesicles with an internal aqueous
phase.’’ The vesicles can differ in size (diameter about 15–3500 nm) and shape (single
and fused particles). At a given chemical composition, these parameters strongly depend
on the process of preparation. Very often the preparations are metastable. That means the
state of free enthalpy is not in an equilibrium with the environment. As a result the vesicles
change their lamellarity, size, size distribution, and shape with time. For example, small
vesicles tend to form larger ones and large vesicles smaller ones. Fortunately this is mostly
not critical for quality because the properties of the phosphatidylcholine, which the vesicles
are based on, remain unchanged as a rule. Nevertheless the stability seems to be best
in a range of about 100 to 300 nm. That is the case of pure aqueous dispersions of highly
enriched (80–100%) soy phosphatidylcholine.
In a complete formulation together with further ingredients, other influences like
compatibility, concentration of salts, amphiphilics, and lipophilics play an important role.
Therefore, it is often very difficult to prove the existence of liposomes, e.g., in a gel
phase or a creamy matrix. However, this is more a marketing problem than a problem of
effectiveness of the formulation. Today we can assume that the effectiveness of phosphatidylcholine
is based more on the total chemical composition of the cosmetic product and
less on the existence or nonexistence of the added liposomes. This may seem curious, but
is in fact the reality.
Of course, formulations are very effective in particular when consisting of pure
liposomal dispersions bearing lipophilic additives in the membrane spheres and/or hydrophilics
in the internal and external aqueous phases within the range of their bearing capacity.
In this respect, there has been an intensive search to increase the encapsulation capacity
of liposomes for lipids because consumers are used to applying lipid-rich creams. Efforts
were made to add emulsifier to the liposomal dispersions to stabilize higher amounts of
lipids. Formulators now know that the compatibility of liposomes with regard to emulsifiers
is generally limited, more or less. On the other hand, additional emulsifiers have a
weakening effect on the barrier affinity of phosphatidylcholine. They cause the phosphatidylcholine
and the lipids to be more easily removed from the skin while washing. In this
respect there is only one rational consideration: to make use of nanoemulsions consisting
of phosphatidylcholine and lipids instead of liposomes. Nanoemulsions are a consequence
of the observation that oil droplets can fuse with liposomes when the capacity of bilayers
for lipids is exhausted [8]. Further increasing the lipid/phosphatidylcholine ratio and using
high-pressure homogenizers lead to nanoemulsions. Nanoemulsions consist of emulsionlike
oil droplets surrounded by a monolayer of phosphatidylcholine. The advantage of
nanoemulsions is that they allow formulations to tolerate more lipids and remain stable.
Also, additional emulsifiers are not needed.
Liposomal dispersions based on unsaturated phosphatidylcholine are lacking in stability
against oxidation. Like linoleic esters and linoleic glycerides, these dispersions have
to be stabilized by antioxidants. Thinking naturally, a complex of Vitamin C and E (respectively,
their derivatives like acetates and palmitates) can be used with success. In some
cases, phosphatidylcholine and urea seem to stabilize each other [9,10]. Moreover, agents
that are able to mask traces of radical-forming ions of heavy metals, like iron, can be
added. Such additives are chelators like citrates, phosphonates, or EDTA. Alternatively,
the unsaturated phosphatidylcholine can be substituted by a saturated one like DPPC or
hydrogenated soy phosphatidylcholine, which should be favored with regard to its price.
Because of the higher phase-transition temperature, liposomal dispersions based on hydrogenated
material are more sophisticated in their preparation and are reserved for pharmacological
applications as a rule. An interesting new development in the field of cosmetic
compositions with hydrogenated soy phosphatidylcholine is the Derma Membrane Structure
(DMS)-technology [11]. DMS stands for cream bases (technically the creams are
gels) containing hydrogenated soy phosphatidylcholine, sebum-compatible medium chain
triglycerides (MCT), shea butter, and squalane. In addition to liposomal dispersions and
nanoemulsions, DMS is a third way to formulate phosphatidylcholine with hydrophilic
and lipophilic compounds free of further emulsifiers (Fig. 3). DMS is water- and
sweatproof and therefore suitable for skin protection and sun creams without using silicones
or mineral oil additives. It can easily be transformed into other final products by
stirring at room temperature together with liquid lipids and/or aqueous phases.
As previously mentioned, DMS is predestined for skin protection, but by addition of
nanoemulsions and/or liposomal dispersions DMS can easily be enriched by unsaturated
phosphatidylcholine containing esterified linoleic acid. The resulting products are creamy,
stable, and anticomedogenic. The effect of pure DMS basic creams on skin moisturizing,
smoothing, and tightening are still significant several days after finishing the application.
Liposomes, nanoemulsions, and DMS have to be preserved. This may be a problem,
because phosphatidylcholine (lecithin) inactivates most of the conventional preservatives
[12]. On the other hand, preservatives should not be penetrated in the skin to prevent
irritation and sensitization. Therefore, glycols like propyleneglycol, glycerol, butyleneglycol,
pentyleneglycol, hexyleneglycol, sorbitol, and their mixtures are the compounds of
choice. These polyols show a moisturizing effect at the same time.
One of the reasons to substitute phosphatidylcholine by polyglycerols and other
synthetic derivatives at the beginning of the liposomal developments was its hydrolytic
instability in aqueous preparations for longer periods of time and at higher temperatures.
In fact phosphatidylcholine, like other glycerides, is attacked by water to form lysophosphatidylcholine
and free fatty acids. But the cleavage of the glyceride bond occurs mainly
at a pH greater than 7, so formulations in the range of pH 5.5 to 7 are sufficiently stable for most purposes. It is possible that hydrolysis depends on the amount of additional
surface active compounds. That is another reason to use liposomal dispersions without
additional emulsifiers.
AVAILABILITY
As previously mentioned, liposomal dispersions are a very comfortable method to use to
work phosphatidylcholine into cosmetic formulations to obtain its superior spectrum of
multifunctionality. Preliposomal fluid phases up to 20% phosphatidylcholine and more
are commercially available [13]. Also, there are references to the use of instant liposomes
in combination with carbohydrates as dry powders [1]. An interesting consideration is
bath oils, which form in situ liposomal dispersions free of additional emulsifiers [14].
These compositions are based on mixtures of phosphatidylcholine, triglycerides, and alcohol.
By pouring the mixtures into water, liposomes are spontaneously formed. These liposomes
strongly tend to adhere to the skin surface. Numerous other methods for preparing
liposomes have been described [1].
APPLICATIONS
Today, most of the experts working in the field of liposomal dispersions agree that liposomes
do not penetrate as intact vesicles into the skin or permeate through the skin. Liposomes
are believed to be deformed and transformed into fragments as a rule. Therefore
size, shape, and lamallarity are not so relevant for the application, but for the chemical
composition of the total formulation.
The multifunctional properties of phosphatidylcholines lead to a number of different
applications. So, formulations with unsaturated phosphatidylcholine are preferred to support
skin regeneration, antiaging, acne preventing, and penetrating other active agents like
vitamins and their derivatives into the skin. Formulations with hydrogenated phosphatidylcholine
may be used for skin and sun protection, but it should be emphasized that in this respect nanoemulsions and DMS are still more convenient. The main components of
choice to prepare ‘‘natural’’ formulations, which are compatible with horny layer, sebum
constituents, and their functions are illustrated in Figure 4. About the role of mineral salts
see Ref. 15.
THE FUTURE OF LIPOSOMAL PREPARATIONS
Liposomal dispersions have proved not only to be innovative and effective cosmetic ingredients,
but also to be a very convenient form to work with phosphatidylcholine. In dermatology,
they will be used with success for preventing and treating several skin diseases.
Complementary formulations are established where liposomal dispersions come up against
limiting factors. Table 2 shows liposomal and complementary formulations in a direct
comparison.
Generally, liposomes, nanoemulsions, and DMS are more compatible with the skin
structure than conventional emulsions usually applied. Compatible means that formulations
do not disturb the integrity of the skin lipid bilayers and are not washed out while
cleaning the skin. In the sense of modern strategies of cosmetics, these formulations get
by with a minimum of auxiliary compounds, which put only a strain on the skin. Moreover,
compatibility means embedding lipids and hydrophilic agents in the horny layer and being
in accordance with the natural situation.
Remarkably, phosphatidylcholine need not be applied in high concentrations because
the experience shows that formulations are stable at lower amounts. Also, there is
a cumulative effect in the horny layer with repeated application of phosphatidylcholine.
In many cases, liposomes, nanoemulsions, and DMS are compatible with each other in a
sense that they can be used as a sort of construction kit. So these formulations are believed
to still have a great future in cosmetic science. How far new findings about the importance
of the choline moiety of phosphatidylcholine [16] will impact skincare research and development
cannot be estimated today.
REFERENCES
1. Lasic DD. Liposomes and niosomes. In: Rieger MM, Rhein LD, eds. Surfactants in Cosmetics.
2d ed. New York: Marcel Dekker, 1997:263–283.
2. Wendel A. Lecithins, phospholipids, liposomes in cosmetics, dermatology and in washing and
cleansing preparations. Augsburg: Verlag fuer chemische Industrie, 1994.
3. Wendel A. Lecithins, phospholipids, liposomes in cosmetics, dermatology and in washing and
cleansing preparations. Part II. Augsburg: Verlag fuer chemische Industrie, 1997.
4. Braun-Falco O, Korting HC, Maibach HI, eds. Liposome Dermatics. Berlin: Springer-Verlag,
1992.
5. Ghyczy M, Nissen H-P, Biltz H. The treatment of acne vulgaris by phosphatidylcholine from
soybeans, with a high content of linoleic acid. J Appl Cosmetol 1996; 14:137–145.
6. Lautenschlaeger H. Kuehlschmierstoffe und Hautschutz—neue Perspektiven. Mineraloeltechnik
1998; (5):1–16.
7. Cosmetic Ingredient Review. Lecithin and Hydrogenated Lecithin. Washington: The Cosmetic,
Toiletry, and Fragrance Association, 1996.
8. Lautenschlaeger H. Liposomes in dermatological preparations. Part II. Cosmet Toilet 1990;
105(7):63–72.
9. Japanese patent 199104364104. Nippon Surfactant Kogyo KK, 1992.
10. German patent 4021082. Lautenschlaeger, 1990.
11. Kutz G. Galenische Charakterisierung ausgewaehlter Hautpflegeprodukte. Pharmazeutische
Zeitung 1997; 142(45):4015–4019.
12. Wallhaeusser KH. Praxis der Sterilisation, Desinfektion—Konservierung. 5th ed. Stuttgart:
Georg Thieme Verlag, 1995:43, 394.
13. Roeding J. Properties and Characterisation of Pre-Liposome Systems. In: Braun-Falco O,
Korting HC, Maibach HI, eds. Liposome Dermatics. Berlin: Springer-Verlag, 1992:110–117.
14. German patent 4021083. Lautenschlaeger, 1990.
15. Feingold KR. Permeability barrier homeostasis: its biochemical basis and regulation. Cosmet
Toilet 1997; 112(7):49–59.
16. Blusztajn JK. Choline, a vital amine. Science 1998; 281:794–795.

VESICULAR SYSTEMS—LIPOSOMES AND NIOSOMES
Definition/Description
Vesicular systems encompass a number of delivery technologies, including liposomes and
niosomes. Both of these systems employ a ‘‘vessel’’ to contain active ingredients within
a formula and to provide controlled delivery of these ingredients. Nacht defines controlled
delivery as a ‘‘system that would result in a predictable rate of delivery of its active
ingredients to the skin’’ [1]. Liposomes are a classic example of this technology, in which
phospholipids are used to create lipid ‘‘capsules’’ that can be loaded with various ingredients.
Although liposomes are enjoying tremendous popularity in cosmetics today, they
have their roots back in the early 1960s. At that time Professor Bangham, at the Institute
for Animal Physiology in Cambridge, U.K., was one of the first to speculate that lipids
such as phosphatidyl choline could be used to create sealed vesicles with bilayer membranes
similar to cell membranes [1]. Niosomes are another delivery technology related
to liposomes; the difference is that, unlike liposomes, niosomes are based on nonionic
surfactants. L’Ore´al pioneered the development of nonionic liposomes using nonionic
surfactants such as polyoxyethylene alkyl ethers combined with fatty alcohols or fatty
acids [1].
Stability Considerations
Liposome and niosome stability may be referred to in terms of leakage of contents, presence
of oxidation products, or changing particle size due to aggregation formation and
fusion. They are rather fragile capsules, and certain precautions must be taken to make
sure that they remain intact and are able to deliver their contents. Leakage can be caused
by mechanical forces like high-shear processing, which should be avoided. Similarly, excessive
heat, which may destabilize the lipid bilayers, should be avoided. Perhaps most
notably, liposomes may be solubilized by surfactants that may be present, and therefore
they are not suitable for use in detergent systems. This is particularly true of systems such
as shampoos and body washes, which contain strong anionic surfactants that can dissolve
the lipid walls. In fact, even though liposomes are often used in creams and lotions, the
emulsifiers used in these formulas may also be enough to disrupt the fragile walls. For
these reasons, many formulators believe that gels are the ideal vehicle for liposomes because
they lack the high HLB (hydrophilic lipophilic balance) surfactants present in many
conventional emulsions, which might disrupt the lipid bilayers [10]. There is hope for
using liposomes in emulsion. K. Uji et al. report that stable liposome suspensions can
be prepared by using a cross-linked acrylic acid/alkyl acrylate copolymer at very low
concentrations, because it can effectively stabilize lecithin liposomes in o/w emulsions
[11]. Furthermore, there is some evidence in the patent literature that the addition of collagen,
albumin, or gamma globulin to the liposomes can decrease the harmful effects of
detergents [10].
In addition to leakage, vesicle systems may fuse together and no longer be available
as discrete units for the delivery of active agents. According to Weiner, such fusion can
occur for several reasons, including preparation below their transition temperature, the
presence of contaminants such as fatty acids and divalent cations, changes in pH, or the
addition of nonelectrolyte hydrophobic molecules [12]. Furthermore, phase separation of
bilayer components can occur upon extended storage. In an excellent review on the subject,
Fox refers to an article by Crommelin et al., that reports on preserving the long-term stability of liposomes. Crommelin discusses the chemical pathways by which phospholipids
can degrade: by hydrolysis of the ester groups or oxidation of the unsaturated acyl
chains. This research points to an optimal pH for liposome stability. For phosphotidylcholine
liposomes, the pH for the lowest hydrolysis rate was found to be 6.5. The stability
of liposomes was further enhanced by using phospholipids with fully saturated acyl chains
(like those made from hydrogenated soybeans, so the opportunity for oxidation is reduced)
[10]. Similarly, liposomes may be stabilized by sugar esters, for example, maltopentose
monopalmitate have been used to improve stability of cosmetic systems [13].
For a more detailed discussion of the morphology of liposomal bilayers, we refer
the reader to Liposomes: From Biophysics to Therapeutics [12]. The author provides an
excellent discussion of the elastic properties and tensile strength of liposomes as well as
the effect of solvents and osmotic effects on liposomal structures.