Lipid Nanoparticles methods, characteristics and applications in drug delivery
Summary
TLDRThe speaker discusses the evolution of their company since 2002, focusing on nanomedicine and solid lipid nanoparticles (SLNs). They highlight the company's expertise in formulation and collaboration on various European projects, emphasizing the importance of surface modification for targeted drug delivery. The talk covers the development of SLNs from first to third generation, touching on applications in cancer treatment, ocular delivery, and nucleic acid delivery. Challenges in regulatory approval and the potential of nanotechnology in treating diseases like retinitis pigmentosa are also discussed.
Takeaways
- 😀 The speaker's company was established in 2002 and specializes in drug delivery systems, focusing on solid lipid nanoparticles (SLN) and nanoemulsions.
- 🔬 The company's expertise lies in formulation and physical-chemical characterization, with no in-house biological characterization facilities.
- 🏥 They have been involved in numerous European projects since the early 2000s, contributing to the field of nanotechnology in pharmaceuticals.
- 📈 There has been a significant shift in the pharmaceutical industry's attitude towards nanomedicine, especially with the COVID-19 pandemic accelerating the approval of liposomal and lipid nanoparticles.
- 🧪 The speaker's team has worked on various projects, including surface modification for targeted drug delivery, risk assessment, and safe-by-design approaches.
- 💊 They have developed different generations of SLN, with the third generation focusing on lipid-drug conjugates and complex lipid mixtures.
- 🔬 The company uses techniques like size exclusion chromatography to understand the composition of their nanocarriers and ensure quality.
- 🧬 They have explored applications in ocular delivery, with a focus on retinitis pigmentosa, and have tested the delivery of nucleic acids for therapeutic purposes.
- 🧪 The speaker discussed the challenges of regulatory approval and GMP development for nanoformulations, emphasizing the need for careful risk assessment.
- 🌐 The company is now focusing on developing products closer to market and providing formulation skills and physical-chemical characterization services to researchers.
Q & A
What is the main focus of the speaker's company?
-The speaker's company is a formulation company specializing in micro, motion solid lipid nanoparticles, lipids, and nano emulsion. They focus on exploiting their knowledge in drug delivery.
What is the significance of the year 2002 for the speaker's company?
-2002 is significant because that's when the speaker's company was established, marking the beginning of their journey in the field of nanomedicine.
What challenges does the speaker highlight in the field of nanomedicine?
-The speaker highlights that while nanomedicine is very promising, it also presents great challenges, especially in terms of regulatory approval and the development of GMP (Good Manufacturing Practice) processes.
How has the COVID-19 pandemic impacted the approval of liposomal or lipid nanoparticles?
-The speaker mentions that the COVID-19 pandemic has helped in the approval of liposomal or lipid nanoparticles, suggesting that the urgency and focus on health during the pandemic may have expedited processes that were previously difficult.
What is the difference between liposomes and solid lipid nanoparticles as described in the script?
-The main difference between liposomes and solid lipid nanoparticles lies in their core. Liposomes have an aqueous core that is more flexible, while solid lipid nanoparticles have a more rigid and consistent core.
What role did the speaker's company play in the early 2000s regarding nanotechnology?
-In the early 2000s, the speaker's company played a significant role in promoting nanotechnology, particularly in overcoming skepticism from pharmaceutical companies and securing funding through various projects.
What is the importance of surface modification in the context of the speaker's work?
-Surface modification is crucial in the speaker's work as it allows for specific targeting, barrier overcoming, and the concurrent logic of drug and diagnostic agent delivery, which is essential for effective drug delivery systems.
What is the significance of the third generation of solid lipid nanoparticles mentioned in the script?
-The third generation of solid lipid nanoparticles signifies an advancement where the core is less rigid and more amorphous, allowing for better drug loading and potentially improved stability.
How does the speaker describe the process of creating solid lipid nanoparticles?
-The speaker describes the process of creating solid lipid nanoparticles by melting lipids, preparing a surfactant in water, warming both phases, mixing them, and allowing the formation to occur spontaneously, followed by cooling and dispersion.
What is the role of size exclusion chromatography in the characterization of nanoparticles as per the script?
-Size exclusion chromatography plays a vital role in understanding the real composition of the carrier, especially in systems with surfactants, as it helps to identify the presence of micelles and different natures of particles.
What are some of the applications of nanotechnology in drug delivery discussed in the script?
-The script discusses various applications of nanotechnology in drug delivery, including targeted drug delivery, overcoming biological barriers, and the development of ocular applications for conditions like retinitis pigmentosa.
Outlines
🧪 Introduction to Nanomedicine and Company Background
The speaker begins by expressing gratitude for the invitation and introduces the topic of nanomedicine, emphasizing the company's focus on solid lipid nanoparticles (SLNs) and nanoemulsions. The company was established in 2002 and has a history of involvement in significant projects related to nanomedicine. The speaker, an engineer by background, shares their journey into nanomedicine in the early 2000s, highlighting the evolution and current challenges of the field. They also touch on the impact of the COVID-19 pandemic on the approval process for liposomal and lipid nanoparticles, noting the increased interest and challenges in nanomedicine.
🔬 Solid Lipid Nanoparticles (SLNs) and Their Evolution
The speaker delves into the specifics of solid lipid nanoparticles (SLNs), discussing their development from first to third generation. They explain the structural differences between liposomes and SLNs, focusing on the core composition and surface properties. The importance of surface characteristics in drug delivery is emphasized, as it influences the particle's ability to reach the desired location at the right time. The speaker also discusses various techniques for creating SLNs, including high-pressure homogenization and microemulsion methods, and the importance of understanding the particle's physical and chemical properties for effective drug delivery.
🧬 Applications and Research in Nanomedicine
This section covers the speaker's company's involvement in various research projects utilizing SLNs for drug delivery. They discuss the use of SLNs for targeted drug delivery, highlighting a project where SLNs were modified with malamide to improve uptake. The speaker also mentions projects involving the delivery of nucleic acids and peptides, such as an approach to treat retinitis pigmentosa using an inhibitor of ceramide synthesis. The potential of nanotechnology in ocular applications is also explored, with a focus on the challenges and successes in developing nano-based products for this field.
👨⚕️ Clinical Applications and Future Directions
The speaker discusses the clinical applications of their research, including the use of SLNs for the delivery of melatonin and other drugs. They highlight the benefits of nanoformulations in improving drug absorption and efficacy. The challenges of regulatory approval and the transition to Good Manufacturing Practice (GMP) for nanoformulations are also addressed. The speaker concludes by positioning their company as a resource for researchers, offering formulation skills and physical-chemical characterization services to support the development of nanomedicines.
📈 Summary and Future Outlook
In the final paragraph, the speaker summarizes the company's journey and contributions to the field of nanomedicine. They reflect on the evolution of their work from research to product development, emphasizing a shift towards more market-oriented projects. The speaker also acknowledges the challenges faced in the industry, such as regulatory hurdles and the need for GMP compliance. They end on a hopeful note, expressing a desire to continue contributing to the advancement of nanomedicine and supporting researchers in their quest to develop effective and safe nanoformulations.
Mindmap
Keywords
💡Nanomedicine
💡Solid Lipid Nanoparticles (SLN)
💡Liposomal Nanoparticles
💡Drug Delivery
💡Surface Modification
💡Nanoemulsion
💡Particle Characterization
💡Biological Characterization
💡Regulatory Challenges
💡Ocular Application
Highlights
The company was established in 2002 with a focus on drug delivery systems.
The speaker emphasizes the evolution of the field of nanomedicine since the early 2000s.
The impact of the COVID-19 pandemic on the approval of liposomal and lipid nanoparticles is discussed.
The company's location in Turin and its role as a formulation company specializing in drug delivery are highlighted.
The company's involvement in numerous European projects focusing on nanomedicine is mentioned.
The transition from traditional drug carriers to lipid nanoparticles is explained.
The differences between liposomes and solid lipid nanoparticles are outlined.
The development of solid lipid nanoparticles from first to third generation is detailed.
The importance of surface modification for specific targeting in drug delivery is underscored.
The challenges and promises of nanotechnology in drug delivery are discussed.
The company's focus on risk assessment and safe by design approaches in recent projects is noted.
The use of nanotechnology in ocular applications and the potential for treating retinitis pigmentosa is explored.
The development of a formulation for the delivery of meriocine to reduce photoreceptor degeneration is described.
The company's work on nucleic acid delivery systems, such as the DNA Trap project, is highlighted.
The potential of nanoformulations for oral delivery of drugs like melatonin is discussed.
The regulatory challenges and the move towards GMP development in the field of nanomedicine are addressed.
The company's current focus on developing products closer to market and the shift from research to development is mentioned.
The speaker concludes by positioning the company as a craftsman of nanomedicine, offering formulation skills and characterization services.
Transcripts
thank you very much for the the intro
i thank you very much for the invitation
just a little uh a premises that i have
to i want to do
um
so um
we are in a very different position
comparing also to what described the
uh
for my
my previous representatives
my talk we take care about our history
much more we we was born in 2002
so we will uh i will represent it will
be the platform of sln which is that a
from where michael marshall is solidly
pinata particles from
from where our patents and papers came
from
some general compasses and some simple
uh summary in last application
and then few words on nano emulsion
uh my premises was to be that i'm um can
you listen me
yes yes
okay
um my premises is that
in the
i'm an engineer so i'm not a biologist a
and neither a a chemical well
good chemistry
um i do a lot of many other things uh
before in my life and then i felt in
love with with nano medicine in the
early 2000s where that situation were
very very different from now
uh the field is really huge especially
with leaping nanoparticles uh vasin are
an example now
um so i have to focus a little bit and i
and i prefer to focus on our system
although is
a particular one
and um
and then i have to say that the vasin
i spoke with people uh in
this area who is working uh
in the raw material area i can
say much more
and they confess me how the kovid
the pandemic helps in uh approval of a
liposomal or let's say of lipid and
nanoparticles
and how difficult was since uh
some years ago just to to manage for
registration of a pure
liposomes for example so the challenges
is huge
nano is very promising but challenges is
great
uh the first um
the first things is just another actor
we established in 2001 precisely coming
from the university of torino
we are located in torino in environment
park in that position we are a
formulation company and we was just born
to exploit the property know how and ib
in drug delivery
we are fully independent and very very
small our facility is a kit for
formulation
but we have no uh biological
characterization so all the data we show
about uh about characterization in
biology is in biology is coming from
other teams so we participated into a
lot of project to do that we've got a
small green room and we are certified
iso
9001 2015. our main skills in micro
motion solid lipid nanoparticles lipids
to bigger particles and nano emulsion
um
here is uh the
all the the project in which we have
been involved so we have a very very big
big participation to the european
movement about uh about nano let's say
since the origin
uh so in 2000 in the early 2000s was
very difficult to speak with with the
pharmacy pharmaceutical company about
nano
uh their attention was okay it's
promising but we have to see
and so we we we play a role to we also
for for surviving for money let's say
for financial point of view with all
this project in fp6 with the local
government and the italian government
now we are
just focusing on three small i mean
let's say different kinds of project
more focusing on
risk assessment and safe by design
approaches
and we are more in in the research area
with the orbital which is an int in
ocular application what we did is mainly
surface modification for specific
targeting knowledge on barrier
overcoming and contemporary logic of
drug and diagnostic agent in the in the
past indulge this project
we are speaking about leaping
nanoparticles so traditional carriers
can be polymeric and oil and water
emulsion then we're speaking about lipid
lipid matrix so lipid nanoparticles
uh and we i put on on the left the
difference between a liposomes and a
solid dipping nanoparticles so mainly
the surface is the same probably uh very
similar with the
with the phospholipid head on the
outside uh the difference is in the core
so we got an aqua score for probably
more flexible in case of of the liposome
more rigid a little bit and more
consistent with solid lipid
nanoparticles
uh i want to i want to remember that
in the in the if you if you're looking
in scopus most of the papers you can
find in the early in the early in the
early moment about solid dipping on the
particles
uh we we give a great contribution
because at the moment the team was
working hardly on
application of the system and most of
papers whereas in cancer application i
know most of you can be interested in
cancer i invite you to to see and
contact with me for for
for uh bibliography and so on
um
then later we
we moved to to application
from different kinds of applications at
the time we work on dr rubis in uh and
and pacquiao
and a lot of other either rubicin
and a lot of other people even
cholesterol beauty rate
um
coming back to lipid now the particles
um
we are speaking about solid lipid
nanoparticles so the first
the first stage of solid dipping on the
particles was mainly
a solid core uh drug is inside and the
external was in a different way the
second generation uh work more on uh
on making the the core less rigid let's
say less crystalline so
uh a more for state there was was the
the the to to
to work on and now we are the third
generation at least
uh so the lipid drug conjugates you can
speak about ion pairing you can speak
about the nanoparticle of of complex
lipid mixture
some of them are covalently bound to a
drug
the problem is that the solidification
of the internal core can can can put
away the substances and gives to the
carrier less stability over time
the
the scheme of the of the particle is is
this one so you have got a surfactant
for us is mainly phosphatidylcholine for
this colin
surfactant we
helps to enhance the curvature of the of
of the layer
and the internal phase which is
hydrophobic phase
uh i want to spend a little bit a little
worse on leaping on the particles
because the the the one we are leaking
we are listening and investing are
reported to be lipid on the party
because so now the precision for example
report these kinds of of images i just
want to see we want to make you the the
all the systems are very border one to
each other most of the time
if you're taking the previous images and
we change the oil with water for example
we obtain a watering in oil in water
microemulsion
or a system on which we play so
uh you you can understand how how close
are all the all the other different
structure we are speaking of course the
surface is the key you know better than
me that in in drug delivery uh what is a
the very important key is always that
the surface in order to understand and
reaching
the right point
in the right moment and right place
uh
just in a smaller
precision uh word about precision so
what is a non-emulsion and what is a mic
promulsion the main difference is uh is
uh for people who
doesn't does not know
is that the non-emulsion is a is a
thermodynamically unstable system so
over time it is probably can can can
brought you to separated phases why
the micro martian
is is a thermodynamically stable system
and is very difficult to be
separated in phases all the time
so uh i bet that's
something a few words about critical
missile concentration hydrophobic like
without the hlb and craftpoint i mean
all things that you know
very well
we work of course with a stronger
stronger surfactant
with particular hlb in order to avoid
the the presence of
energy
strong energy solid depending on the
particles here are reported the main
the main the main pattern all over you
you see that the first one is isgasco
and uh and mueller in germany so that
the two guys were reaching the same
system with two different kinds of uh
approach by war micromotion and high
pressure organization then the methods i
have come
all over a very
a lot of them in order to do the same
the same kind of system
uh
very briefly the solution of article by
by by war micromotion you have to melt
lipid of course in which you are going
to load the the drug you you prepare the
the surfactant in water you warm up both
both the two phases you mix the two
phases and the deformation is
spontaneous of course you have to study
for for having the right ratio in in
surfactant and lipid
and then you can go for micro motion
cool dispersion in in cool temperature
you just disperse the the the the small
drops of a micro mulching and you obtain
the sln formation it's quite
system
that's that's the main basis of our
system in the in the beginning
the characterization techniques are the
usual one for uh for the one uh for for
uh
for all the nano and the nano staff
let's say i point out your your your
attention especially on size exclusion
chromatography
which is very important to understand
the the real composition of the of the
of the of the carrier because uh
being this kind of system with
surfactant
sometimes the micelles uh and and the
different kinds of nature can be can be
present and and size exclusion gives you
good good
good way to understand more about your
system
uh so starting from from these kinds of
uh
of method or pardon can i come back
uh
the main characteristic are the range of
dimensional range it can be very small
to a little bit more uh big i reported
these kinds of images to understand is
one microns that so that they the
composition
although is a simple method without any
sorting any pressure any high pressure
homogenizer inside is quite homogeneous
in size distribution
you can watch by tangential filtration
in order to remove the surfactant you
can freeze dry you can sterilize by
different kinds of things
of methods and of course you've got the
possibility to play on surface for
charge modification just to change it to
positive or negative and to insert
precursor for bioconjugation
uh
i'm speaking about few things about some
some projects uh this one was uh in in
that project
so new sln we studied there the new sln
matrix the third generation uh mixture
cholesterol esters
uh we worked to stabilize the the
formulation in order to apply the
bioconjugation uh
so we set up the thai mala by by
conjugation
we set up this the
exclusion chromatography in order to
understand how much of the of the drug
you want to join
when a link to your particle is
effectively linked to the particles and
we tested antibody and the peptide the
derivative of our body for protein which
is reported in this paper please go and
and see the papers above for you will be
more easy to understand all the
biological the biological
characterization
so what we we did is just to set up the
particles so to put malamide in outside
and then to go for the conjugation of
the this peptide which is a
monoapoy residue
of the human happy
we purify for uh through transgender
filtration and uh for size exclusion
chromatography uh mainly the results say
that uh in uh
in the uptake so we
as by the previous uh the previous uh
slides
for for a good for a good
studies of the behavior of the particle
we read your label the particle with two
radio or radio label
uh treats yuma and
c14
and two fluid eyes in order the
contemporary uh looking at the
the spices at
the levels can confirm that you are not
looking at something that is
moving by himself
which is quite typical in these kinds of
uh um
of study
so the uptake confirmed that that in in
presence of the apoe the uptake was
definitely
bigger than than with a system only sln
so to have the comparison we just use
cysteine
and
in a transverse insert mimicking the
blood frame barrier
uh the passage
due to the
the peptide was was definitely um
bigger
uh comparing to the the
unfunctionalized carrier
in vivo administration
has been tested by intraperitoneal
intravenous uh and intertracted uh in uh
installation
and the most promising uh show to be uh
the intratracker installation as you can
see by the last
uh images
in uh in the down in
in below
uh
with these kinds of things we work also
in other in other project like magnifico
in order to test the fragment of
antibody afro synthetized by dompe and
for another peptide uh
which is lock with a candiola hospital
here in torino
uh in a band project
our main focus is now the
um
autonomic application i haven't seen in
the previous presentation yet the
authentic application i do believe that
also in ocular there's a huge huge room
for for a nanotechnology uh nano based
product
um rick knightis pigmentosa is a huge he
uses a big big
disease
affected
one to four thousand people and one of
the major causes of blindness in in the
developed world
the team was a biochemist
neuroscientist electrophysiologist and
and myself for photo formulation aspects
uh the problem the problem is that uh so
the problem that they keep the the
starting of the of the approach was that
um the ceramic ceramide contributes to
the the as it has got the prosthetic
role uh
messenger in uh in neuronal pathologies
like reported here from from the from
the paper
of course the increasing level of the
novel synthesis can be associated with
the beginning of that of the
cone and
and roads
in
in the model
uh
of course appropriately of ceramide are
necessary for differentiation
but um
from the study they
they start
at the beginning they show that in rd
model
uh the level of ceramide effectively was
increasing over over time in the in the
in their ld10 mice model
so uh
the guys the the the scientists find out
the meriocine which can block the
synthesis uh so it's a is an inhibitor
of the synthesis of the normal synthesis
of ceramide
by uh
inhibiting the strain permitting
transferases
and uh go for testing uh this approach
in order to reduce the the photo
degeneration in the in the model so that
the target was the nervous synthesis of
ceramide
uh
the the problem is that uh sorry in in
the previous uh in the previous slide
you can see that they tested by travital
injection
well the the demise was about 10 grams
uh at the age age of uh 14 days so they
couldn't test for for longer uh long
administration of the of the same drug
and that's the reason why they they come
to look if nanotechnology can give an
answer to that
so we set up by our systems
a
[Music]
formulation
which was characterized in in very good
way this is the the the
the dls of the of the formulation of the
meliosa in sln
uh which is uh very small in a diameter
and as you can see the pdi was was very
good so very easy to be filtrated for
for sterility
and uh finally they can administer for
20 days to to turrets to mice sorry
and prove uh effectively that the
decrease of photoreceptor survival after
chronic treatment can be demonstrated
because they give that every day three
times a day
to the to the mice the the for the meals
in formulated in solid lipid
nanoparticles
uh
we went uh they went through of course
and they repeated the second so the
second paper comes from this
up to seven so for for um
60 days of administration and can show
that the the roads effectively uh
maintain the
are maintained much more better uh
comparing to the the control so the the
normal uh normal stage
of course we are speaking of model for
example i i hope that these kinds of
of things would be will be made easier
from initiative like the previous
described before
because one of the projects in in these
kinds of uh
of disease is that it takes so long time
to be demonstrated that the key point
that we work a lot but it was very
difficult to find
money to to to get this this uh this
project a little bit ahead
other project in which we work with
nucleic acid delivery
was the dna trap
where the company procata proposed his
approach with the transcription factor
decoy to be given to bacteria in order
to block the synthesis of protein once
you are touching the where you are
biting the the bacteria himself
so giving the possibility not to having
a reaction by the bacteria
they've got these kinds of molecule with
the bola amphiphile uh we were taking uh
in the
in the
team
uh for the formulation for
one of the possible formulation tests in
the project
so we set up as well three or four kinds
of uh of sln and we went for a layer by
layer coating strategies
uh so we we use the the particle for a
layer by layer so we apply the the
things on the outside of the particle
not inside the the vectors
different kinds of particles have been
done i'm going fast because i'm going to
out of time
and this is the the formulation so
you can see that effectively the tfd
is kept by by the formulation and uh
treating with the dnas
uh the asterisk means the stars means
that we run the the the tft once we
remove from the
from the formulation treated with dnas
is intact after after the uh
the incorporation by the system meaning
that we are uh blocking and protecting
the uh
the diffract the the nucleotide
um
short short things about uh approach in
uh
oral delivery we are speaking about uh
uh
melatonin this paper has been published
uh quite recently so people uh in
in hospital talk took this uh these
kinds of
drugs formulated in uh transdermal and
horse
also is the comparable between in
formulation in sln and in normal
available uh
melatonin
of course they did it demonstrate that
the entire administration of melatonin
can
can be obtained and better
by formulation even by transdermal so by
formulation of
micro emulsion
directly on the skin of the patient
this one was a previous paper on
melatonin in which you can see how it it
the area under the curve once you give a
melatonin sln
and even when you see the the
transdermal application so after many
hours the level it was uh
going up but even when you when the
pitch removal was was actuated the level
still remain very high so meaning that
that there are rooms to to understand
the better uh
dossier for of this forum
uh i go through i mean i want just to
mention describe the which has been done
in 2007 you can go for foresee the
the approach with was with an anti-agf
reporting that this one was made by uh
oil top watering oil in water micro
marsh a multiple micromotion in which
the oligonucleotide was inserted inside
the formulation inside the core of the
of the nanoparticles
now we are just setting up these kinds
of
we are working more on non-emulsion that
is our work we are not working anymore
that much in research if i can say we
are
much more working on a
development a small product but more
close to market the problem of my
previous
colleague
clearly explain how is the risk in this
field
uh when you're speaking about uh about
nanoformulation
the regulatory is very very difficult to
face
and also for for going to to gmp
development this all the our faces that
you have set up for these kinds of
things uh these are the formulations we
are studying now with the different
kinds of uh of uh other projects but
always the same nano emulsion
uh
for for autonomic product
uh we inserted the malay might also in
these kinds of things also for research
projects uh we tested this uh as an
appendix of course
uh i'd like to see to show these kinds
of images let's say the few years ago
we feel much more like this and now we
are feeling much more like
the the guy on the right
uh but
so we are just moving to be a sort of
crafter of nano uh that's what i like i
like to
to speak about ourselves
um
but we are proposing no senior
researcher and assisting them with
formulation skills and physical chemical
characterization from diseases and one
stop low cost renting formula
if i can suggest
and
i guess this is old and i thank you very
much for your kind attention
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