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Newsletter
Volume 1, Number 1
September 2006
Newsletter Volume 1, Number 1
September 2006
Page 2
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Introduction
The newsletter of the Phospholipid Research Center
will be the primary publication organ. It will inform
about the Center and all aspects of phospholipids in
the following columns:
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Phospholipid Research Center news
News
Conference Reviews
Analytical Column
If you want to suggest new column items, please send
an e-mail to [email protected].
The newsletter will be published three times a year. If
you are looking for additional information, please take
a look at our homepage
www.phospholipids.net
there we will provide information in shorter intervals.
Phospholipid Research Center news
Aims of the Phospholipid Research Center
Phospholipids are outstanding excipients and active
ingredients for pharmaceutical use. They are
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physiologically safe
toxicologicalyl safe if used in the appropriate purity
natural and bio-degradable substances
suitable for all systems when used in the adequate
composition
Phospholipids are already widely used in registered
pharmaceutical formulations worldwide. However, their
use could still be further extended as they might be
able to replace almost all other emulsifiers and
surfactants.
To build up the knowledge about phospholipids the
independent Phospholipid Research Center located in
Heidelberg, Germany, was founded which will be
dedicated to enhance the use of various kinds of
phospholipids by:
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Promoting the use of phospholipids in
pharmaceuticals and
Distribution of the information available among
scientists and practitioners
The Phospholipid Research Center activities will
extend the possible utilization and physiological
significance of phospholipids of all kinds (i.e. natural,
hydrogenated, synthetic, and modified phospholipids),
and combined products of phospholipids as excipients
and active ingredients in pharmaceuticals.
The Phospholipid Research Center has been founded
as a non-profit organisation and will intend to promote
and provide a foundation for the use of phospholipids
in pharmaceutics. Thus, information and assistance to
scientists and practitioners will be provided by
associates and external advisors of the Phospholipid
Research Center, either free of any charges or at a
cost.
The Phospholipid Research Center intends to become
a primary point of contact address regarding all
phospholipid-related questions and for all relevant
_____________________________________________________________________________________________________________________
Phospholipid
Im Neuenheimer Feld 582
Phone +49 (0) 6221 - 5888360
Forschungszentrum / Research Center
D-69120 Heidelberg
Fax
+49 (0) 6221 - 6515665
Heidelberg
www.phospholipids.net
Newsletter Volume 1, Number 1
September 2006
Page 3
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areas of expertise. Examples of areas of technical
competency will include:
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technological aspects
physiological aspects
toxicological aspects
analytical aspects and development of analytical
standards
stability of phospholipids
interactions of phospholipids and active
pharmaceutical ingredients
new applications
new manufacturing processes of phospholipids
The Phospholipid Research Center will be familiar with
regulatory requirements of registration authorities
worldwide and will participate in the creation of
monographs and guidelines as an advisor in regulatory
matters.
The Phospholipid Research Center asks the experts in
the relevant areas of expertise for their contribution to
foster the dialog between the sectors all over the
world.
The Phospholipid Research Center promotes research
projects in various areas through:
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requests of proposals for scientific projects to
scientists
particular efforts in promulgation of the
development and use of phospholipids in
pharmaceutical products
sponsoring of dissertations and research projects
in academia
Membership Benefits
The benefits of a membership in the Phospholipid
Research Center shall include at least the following:
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Scientific exchange
Access to scientific compositons
Newsletter
Member fees for conferences and workshops
Procurement of analytical services
Scientific Board
The Phospholipid Research Center was founded by
famous international scientists together with the
companies Lipoid GmbH and Phospholipid GmbH.
It gains the support of the Scientific Board which
consists of famous, experienced scientists from the
different fields of expertise.
The Scientific Board will ensure the scientific expertise
of the Phospholipid Research Center. The members of
the Scientific Board will apprise the scientific
compositions and publications of the Phospholipid
Research Center, will contribute in the Newsletter and
will recommend proposals for scientific projects.
Outlook
In the first six months the Scientific Board will foster the
creation of first scientific compositions, request of
proposals for scientific projects and make first plans for
a Phospholipid Congress.
_____________________________________________________________________________________________________________________
Phospholipid
Im Neuenheimer Feld 582
Phone +49 (0) 6221 - 5888360
Forschungszentrum / Research Center
D-69120 Heidelberg
Fax
+49 (0) 6221 - 6515665
Heidelberg
www.phospholipids.net
Newsletter Volume 1, Number 1
September 2006
Page 4
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Industry news
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Hana Biosciences Initiates Marqibo® Phase II
Clinical Trial in Relapsed or Refractory Acute
Lymphoblastic Leukemia (ALL)
Marqibo ® (vincristine sulphate sphingomyeline
liposomes injection)
Celsion adds clinical trial site for lead drug
The company has also initiated a Phase I study of
ThermoDox for the treatment of breast cancer.
ThermoDox combines a heat-activated delivery
mechanism with an existing cancer treatment drug.
Skye Pharma announces First European
Approval of DepoDur ™.
DepoDur ™ for the treatment of pain following
major surgery. DepoDur ™ is a novel single dose
sustained-release injectable formulation of
morphine.
Biomira announces final Phase 2b survival
results of Stimuvax ®
(formerly known as BLP25 Liposome Vaccine) trial
in patients with non-small cell lung cancer.
Dainippon Sumitomo Pharma receives
Approval for Antifungal Agent AmBisome.
A lipsomal formulation of the antifungal agent
amphotericin B, from the Ministry of Health, Labor
and Welfare - Japan
Aradigm and Canadian Department of National
Defence Extend AERx Liposomal Ciprofloxacin
Development Program
The extension calls for additional funding of
$662,500 CDP from DRDC to execute a preclinical
efficacy study of inhaled liposomal ciprofloxacin for
post-exposure prophylaxis against inhalational
anthrax.
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Acusphere Completes Enrolment in Second
Phase 3 Clinical Trial
RAMP-2 (Real-time Assessment of Myocardial
Perfusion-2), for the Company’s lead product
candidate AI-700.
AL-700 is an investigational ultrasound contrast
agent. A-700 is a dry powder consisting of small,
porous microspheres filled with a perfluorocarbon
gas. The compositon and structure of the
microsphere, which contains a phospholipid.
Hemophilia – Promising Early Clinical Trials for
longer Acting Kogenate®.Product BAY 794980
BAY 79-4980, is a unique combination of
recombinant factor VIII (rFVIII) with Zilip Pharma’s
proprietary synthetic polyethylene glycol (PEG) –
coated lipsomes.
Study shows Bioral® Delivery Technology
Delivers
(Nanocristalline Structure termed a “Cochleate”)
Influenza siRNA Therapeutic and Reduces Virus
Levels by 200 Times in Mice
IDEA announced it had reacquired North
American rights
to the IDEA – 033 Ketoprofen – Transfersome gel
to treat knee pain associated with osteoarthritis,
from the McNeil Consumer and Specialty
Pharmaceuticals subsidiary of Johnson&Johnson.
The next step is to submit a marketing application
in Europe early next year.
Biomira Stimuvax ®
(L-BLP25) Prostate Cancer Study Results
Published
BLP25 Liposome Vaccine or L-BLP25, could slow
rising Prostate Specific Antigen (PSA) levels in
some post-surgical prostate cancer patients,
potentially delaying the need for initiation of
androgen deprivation therapy (ADT).
_____________________________________________________________________________________________________________________
Phospholipid
Im Neuenheimer Feld 582
Phone +49 (0) 6221 - 5888360
Forschungszentrum / Research Center
D-69120 Heidelberg
Fax
+49 (0) 6221 - 6515665
Heidelberg
www.phospholipids.net
Newsletter Volume 1, Number 1
September 2006
Page 5
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Literature report
A more detailed literature report can be found at
www.phospholipids.net
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Development of liposomal capreomycin
sulphate formulations: Effects of formulation
variables on peptide encapsulation
Ricci, M.; et al., Int. J. Pharm 2006, 311,172-181
DPPC/ DPPG (90:10 w/w) lipsomes were found to
provide the highest capreomycin sulphate content.
These liposomes are useful for a possible
application in aerosol antitubercular therapies.
Lysophosphatidic Acid is constitutively
produced by human peritoneal mesothelial
Cells and enhances adhesion migration, and
Invasion of Ovarian Cancer Cells
Ren J.; et al., Cancer Res. 2006, 66(6) 3006 –
3014
Lysophosphatidic acid (LPA) is both a potential
marker and a therapeutic target for ovarian cancer.
Electrospray mass spectrometry of lipids
Postle, D.; Lipid Technol. 2006/18(8) 181 – 185
Electrospray ionization mass spectrometry (ESIMS) has revolutionized approaches to detailed
analysis of molecular species compositions of
intact lipid molecules. It has unrivalled sensitivity
and detail of information provided, and it is very
rapid and can often be performed with no
chromatographic separation.
Formulation and Characterization of Lipid –
Coated Tobramycin Particles for dry Powder
Inhalation
Pilcer, G.; et al., Pharmaceutical Res. 2006, 1 – 10
Lipid coating (hydrogenated phosphatidylcholine)
of trobramycin formulations resulted in a reduced
agglomeration tendency and in high fine particle
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fraction values, thus improving drug deposition.
Treatment of cystic fibrosis by inhalation.
US Pat. Appl. 20060165606; July 27, 2006
Nektar Therapeutics
A pulmonary delivery medicament comprises a
plurality of particulates, the particulates comprising
a structural matrix and a water insoluble and/ or
crystalline active agent. Preparation of hollow
porous particles of gentamicin sulfate by spraydrying, hydrogenated phosphatidylcholine,
gentamicin sulphate, perfluorooctylbromide,
perflubron
US Pat. Appl. 200601165744; July 27, 2006
NeoPharm Inc.
Combination liposomal formulations
Comprising a physiologically acceptable carrier
and two or more agents encapsulated in a
liposome. Liposomal doxorubicin was prepared for
clinical administration by simple vortex mixing of a
vial containing 40mg of cardiolipin-liposome
lyophilizate and 2.5ml of a doxorubicin solution
previously prepared in 0.85% NaCl at mg/nl.
US Pat. Appl. 20060178394; August 10,2006
Vectura Ltd.
Pharmaceutical compositions comprising
apomorphine for pulmonary inhalation
Micronized apomorphine and hydrogenated
phosphatidylcholine
_____________________________________________________________________________________________________________________
Phospholipid
Im Neuenheimer Feld 582
Phone +49 (0) 6221 - 5888360
Forschungszentrum / Research Center
D-69120 Heidelberg
Fax
+49 (0) 6221 - 6515665
Heidelberg
www.phospholipids.net
Newsletter Volume 1, Number 1
September 2006
Page 6
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Conference review
33rd Annual Meeting and Exposition of the
Controlled Release Society
July 22 – 26, Vienna, Austria, 2006
On 22 – 26 July the 33rd Annual meeting and
exposition of the Controlled Release Society was
held at the Austria Center in Vienna, Austria.
The conference included a number of lectures and
posters dealing with the use of phospholipids. About
sixty of the 1100 submitted abstracts describe
research with or about phospholipids. Most of them
concern to liposomes like the presentations of Dr. D.
Reimer et al. (Liposome Formulation of Sparingly
Soluble Compounds), Prof. A. Gabizon (The
Liposome Drug Delivery Plattform in Cancer
Therapy), Dr. A. Wagner et al. (A Novel HIV 1
Vaccine Candidate Based on Liposomes) and Prof.
T. Allen et al. (Nano-lipid Systems: Pharmacokinetics, Pharmacodynamics and Bioavailability).
Although numerous posters dealt with liposomes like
the contributions of Dr. Y. Perrie et al. (The Influence
of Alkyl Chain Length on Liposomal Encapsulation of
Poorly Water Soluble Drugs) and Dr. C. Martin et al.
(Preparation of liposomes by jet homogenisation) or
with sophisticated applications of liposomes like the
research of Dr. M. Brandl et al. (A Novel in vitro
Model for Studying Passive Drug Permeability /
Absorbability: The Phospholipid Vesicle-Based
Membrane).
The presentation of Dr. C. Srinivasan (Intracellular
Tracking of Plasmid DNS with Semi Conductor
Nanocrystal Quantum Dots) and the poster
contribution of Dr. I. Rubinstein et al. (Real time
tracking of actively targeted phospholipid mixed
micelles to human breast cancer cells using quantum
dots) describe the use of phospholipids to
encapsulate quantum dots.
Other contributions described the use of
phospholipids in further delivery systems like for
example nanoemulsions (e. g. Dr. S. Hatziantoniou
et al.: Preparation and physicochemical
characterization of a ceramide containing
nanoemulsion), micelles (e. g. Dr. H. Önyüksel et al.:
Interaction of peptide drugs with sterically stabilized
phospholipid micelles at a molecular level) or solid
lipid nanoparticles (e. g. Dr. A. Attama et al.:
Permeation of Some Model Drugs from SLN
Formulated with Novel Structured Lipid Matrix
Through Artificial Skin Construct).
The meeting confirmed that phospholipids are and
stay important substances for controlled drug release
in approved delivery systems as well as in new,
innovative technologies.
More information about the conference could be
found at http://www.controlledreleasesociety.org.
Information about a special phospholipid
In this column we want to provide information about
special phospholipids. We want to start with a short
definition of the term “lecithin”.
The term lecithin is used to describe fat-like
substances which are derived in the main from oil
seeds like soybeans and rape seeds and minor from
animal tissue and hen eggs.
This lecithin is a mixture of various components with
different chemical and physical properties. The main
components of commercial lecithin are the
phospholipids, which consist of glycerine, fatty acids
_____________________________________________________________________________________________________________________
Phospholipid
Im Neuenheimer Feld 582
Phone +49 (0) 6221 - 5888360
Forschungszentrum / Research Center
D-69120 Heidelberg
Fax
+49 (0) 6221 - 6515665
Heidelberg
www.phospholipids.net
Newsletter Volume 1, Number 1
September 2006
Page 7
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and amino alcohols or carbohydrates due to the
following chemical structures:
Analytical column
Acid Value in Phospholipids
R1H2O
R2H2O
O PO OCH2CH2NH2
OH
phosphatidylethanolamine
R1H2O
R2H2O
+
O PO OCH2CH2N(CH3)3
Ophosphatidylcholine
R1H2O
OH OH
R2H2O
O PO O
OH
phosphatidylinositol
OH
OH
OH
The residues R1 and R2 in phospholipids denote
fatty acids as they appear in the attendant lipids of
the lecithin. Phospholipids of plant origin are
typically highly unsaturated. Phospholipids of animal
origin show very different fatty acid compositions.
In lecithins of plant origin phosphoatidylserine,
phosphatidic acid and glycolipids are present beside
phosphatidylcholine, phosphatidylethanolamine and
phosphatidylinositol. Lecithins of animal origin
contain various sphingolipids and plasmalogens.
In oils the acid value is usually a good indicator for
the hydrolysis or not efficient raffination and shows
the content of free fatty acids (FFA).
In lecithins and phospholipids the usual analytical
method as described in various pharmacopoeae is
not useful because all acidic phospholipids are also
titrated.
Therefore these products have to be purified with a
chromatographic method. Then the oil, free of
phospholipids, is analyzed following the usual
methods for its content of free fatty acids.
If the phospholipids contain only a small amount of
oils, it is useful to quantify the free fatty acids with a
simple thin-layer chromatographical analysis. The
detection limit of free fatty acids is 0.05% with this
method.
If free fatty acids are absent, acidic phospholipids in
their free form can be quantified with this method
easily.
Contact
Phospholipid Research Center
Im Neuenheimer Feld 582
69120 Heidelberg
Germany
Phone: +49 (0)6221 / 5888360
Fax: +49 (0)6221 / 6515665
E-Mail: [email protected]
Web: www.phospholipids.net
_____________________________________________________________________________________________________________________
Phospholipid
Im Neuenheimer Feld 582
Phone +49 (0) 6221 - 5888360
Forschungszentrum / Research Center
D-69120 Heidelberg
Fax
+49 (0) 6221 - 6515665
Heidelberg
www.phospholipids.net