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Are there any functional differences between a micelle and liposome?
It seems to me that they both form "sacks" in which drugs can be
concentrated within. Liposomes are more bubble-like and formed from
bilipid membranes. Micelles are formed from surfactants. Is my
understanding correct?
Would it be safe to say that the FDA guidance on liposomal drugs
applies to micelles?
Also, do any marketed drugs use micelles?
Thanks,
pete bonate
Peter L. Bonate, PhD
Genzyme Corporation
Senior Director, Pharmacokinetics
4545 Horizon Hill Blvd
San Antonio, TX 78229 USA
peter.bonate.-a-.genzyme.com
phone: 210-949-8662
fax: 210-949-8219
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The following message was posted to: PharmPK
>Are there any functional differences between a micelle and liposome?
>It seems to me that they both form "sacks" in which drugs can be
>concentrated within. Liposomes are more bubble-like and formed from
>bilipid membranes. Micelles are formed from surfactants. Is my
>understanding correct?
Dear Peter,
both micelles and liposomes are small vesicles in which drug
molecules can be encapsulated.
In the case of micelles they entrap lipophilic drugs that are relased
by the dilution of the micellar solution in a water environment.
In the case of liposomes both lipophilic and hydrophilic drugs can be
entrapped : lipophilic molecules in the membrane and hydrophilic
molecules in the "cavity". Drugs are released when liposomes fuse
with cell membranes.
This means that a great difference is that micelles should preferably
be considered as drug solubilizers while liposomes ar drug carriers.
Best regards,
Frederic Doc
fdoc.aaa.acriter-consulting.com
www.acriter-consulting.com
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Micelles can hold either hydrophilic or lipophilic drugs depending on
whether they are reverse micelles or not. Functionally they can do
the same thing. I recommend you check out the Valdimir Torchillin's
book "Liposomes, A Practical Approach".
Phil
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Dear Dr. Bonate,
Both micelles and liposomes are vesicular particles that are formed
utilizing molecules that have polar heads and lipophilic tails.
Application-wise, micelles are ideal for formulation of lipophilic
drugs that are otherwise problematic to formulate. Liposomes of the
other side are great for drug delivery and targeting as vesicular
carriers for both lipophilic and hyophilic agents. The utility of
liposomes as drug delivery systems is based on the liposomal
composition and the similarity to cellular membranes.
By virtue of their composition and structural differences as well as
their applications, I think some of the sections in the guidance will
virtually apply to both vesicular systems. For example, some of
chemistry QC, formulation and release QC that apply to liposomes may
(but not always) apply to micelles.
I hope this helps. It would be interesting to hear from FDA
scientists regarding this issue.
Regards,
Murad Melhem, Ph.D.
Cognigen Corporaion
Buffalo, NY
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The functional difference between a liposome and a micelle lies in
the chemistry of their constituents, physiological disposition and
therapeutic benefits.
Micelles are formed from anionic (sodium laurly sulphate), cationic
and non-ionic surfactants (poloxamer) and are primarily monolayered
self-assembled systems, in which preferably a lipophilic drug can be
entrapped. Liposomes on the other hand is formed from natural or
synthetic and preferably zwitterionic surfactants (lecithins) and are
concentric bilayered (peeling onion like) self-assembled system,
which can be loaded with either lipophilic or hydrophilic drugs.
Liposomes are generally administrered by parenteral route (approx. 10
formulations in the market) and is being taken up by RES
(reticuloendothelial system)-rich organs and thus can be targeted to
liver or can be coated with polymers like PEG, and thus remain in the
circulation and thus can be targeted to tumor cells. Preferentially,
the objective of liposomes is to achieve targeting to specific sites
(cells, tissues, organs) and since the technology is quite complex
and expensive, it is primarily reserved for therpeutic indications
like cancer or viral diseases.
Micelles on the other hand, are preferntially administered orally and
release the drug after dilution with the biofluid. No specific uptake
mechansims are involved as in the case of liposomes. The
constitutents of these systems may transiently also influence the
permeability of the membrane and thus benefit the drugs of BCS class
II or IV. Several products are available in the market which range
from micellar to swollen reverse micelle (or microemulsion).
To my understanding FDA guidance on liposomes will not be applicable
to micelles as the disposition kinetics will differ from both the
systems and specific studies needs to be performed on a case by case
basis. However the draft guidance on liposome product can be referred
as a guideline.
thanks and regards,
Vaibhav
Vaibhav Sihorkar, Ph.D
Senior Scientist
Formulation Research Department
Disocvery Research
Dr. Reddy's Laboratories Ltd.
Hyderabad 500 049, India
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Hello Peter,
Micelles are core-shell structures, the core being hydrophobic
(incorporating the hydrophobic drug) and the shell more hydrophilic
(solubilizing the loaded micelle). They are made of amphiphilic
molecules, surfactants or copolymers that self-assemble in a
selective solvent over a threshold concentration refered to as the
critical micelle concentration. These self-assembled nanocarriers can
be engineered to solubilize, target and release hydrophobic drugs.
They are dynamic systems: free surfactant (or copolymer) molecules
are in equilibrium with molecules engaged in the micelle formation.
Upon injection, the flexible hydrophilic corona decreases the
scavenging by the mononuclear phagocyte system. They can have
different morphologies, not only spherical. Size 10-100 nm.
Paclitaxel (Taxol) is a marketed product containing micelles
(Cremophor EL).
Liposomes, as you said, are formed from one or several lipid
bilayers. They usually incorporate molecules that are more
hydrophilic than micelles do, in an aqueous internal cavity. They
are usually larger than micelles (50-900nm). One marketed product is
Doxil (doxorubicine). They can be used to improve drug safety and
administer higher doses.
They can be SUV (small unilamellar vesicles 50-80nm), LUV (large
unilamellar vesicles 600-800nm) or MLV (multilamellar large vesicles,
heterogeneous size). Classically they contain phospholipids,
cholesterol, but they are made of many other components now. They
have been extensively studied. They can be PEGylated also to decrease
the scavenging I mentioned above.
I cannot really help concerning the FDA requirements. I can just
highlight that the excipients used to prepare the 2 dosage forms are
very different.
I hope this can help.
Elvire
Elvire Fournier, Pharm.D, Ph.D.
Preformulation
Serono Pharmaceutical Research Institute
14 chemin des Aulx
1228 Plan-les-Ouates, Geneva
Switzerland
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The following message was posted to: PharmPK
There is an interesting issue coming from liposomes.
It has been demonstrated "in vivo" that an artificial liposome could
fuse with cells membranes which integry and composition (which is
required for a optimal enzimatic and receptor activity and variable
depending on tissues) is strictly controlled by the cell?
Regards to all friends
Dr Roberto Conti
Sigma-Tau
Dep. of Endocrinology and Metabolism
00040 pomezia, Roma
Phone: +39-06-91393322
Fax: +39-06-91393988
e-mail. roberto.conti.-at-.sigma-tau.it
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Dear Phil,
I don't fully agree with you on the fact that both micelles and
liposomes can functionally do the same thing.
My point of view is the following :
Liposomes are drug carriers used to try and target specific tissues
and sites of action.
Micelles are used to enhance the solubility of a drug but are not
able to target as liposomes do.
Regards,
Frederic Doc
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I figured the question raised initially would create some sort of
fire storm. My statement of micelles was really meant in a reference
to emulsions, I mis-spoke.
Regards,
Phil
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