Lipid Nanoparticles methods, characteristics and applications in drug delivery

Summary

The 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

00:00

🧪 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.

05:01

🔬 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.

10:02

🧬 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.

15:04

👨‍⚕️ 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.

20:07

📈 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.

Keywords

💡Nanomedicine

Nanomedicine refers to the application of nanotechnology in medical treatment and diagnostics. It involves the use of nanoparticles for drug delivery, imaging, and other therapeutic purposes. In the video, the speaker expresses their passion for nanomedicine, which they fell in love with in the early 2000s, highlighting its potential in revolutionizing healthcare. The script mentions various projects and applications that utilize nanomedicine, such as drug delivery systems and diagnostics.

💡Solid Lipid Nanoparticles (SLN)

Solid Lipid Nanoparticles are a type of nanoparticle used in drug delivery systems. They consist of a solid lipid core that can encapsulate drugs, with a surfactant layer around it to stabilize the particle. The script discusses the evolution of SLN, from the first generation with a rigid core to the third generation with lipid-drug conjugates. The speaker's company specializes in formulating SLN and has been involved in numerous projects utilizing this technology.

💡Liposomal Nanoparticles

Liposomal nanoparticles are vesicles composed of a lipid bilayer that can encapsulate both hydrophilic and hydrophobic drugs. They are used to improve the solubility and bioavailability of drugs. The script mentions that the COVID-19 pandemic has expedited the approval of liposomal and lipid nanoparticles, indicating a growing recognition of their potential in medicine.

💡Drug Delivery

Drug delivery refers to methods or technologies used to get a pharmaceutical compound in the body to ensure the drug is released in the required dosage and location needed to cure or manage the disease. The video script discusses various drug delivery systems, including SLN and liposomes, which are designed to target specific areas in the body and improve the efficacy and safety of treatments.

💡Surface Modification

Surface modification in the context of nanoparticles involves altering the surface properties of the particles to enhance their stability, targeting ability, or biocompatibility. The script mentions surface modification for specific targeting, which is crucial for directing nanoparticles to the right cells or tissues in the body, ensuring the drug is delivered precisely where it's needed.

💡Nanoemulsion

A nanoemulsion is a mixture of two immiscible liquids, one of which is dispersed in the other in the form of very small droplets (nano-scale). It is used in various applications, including drug delivery and cosmetics. The script discusses the difference between nanoemulsions and microemulsions, emphasizing the thermodynamic stability of nanoemulsions and their potential in pharmaceutical formulations.

💡Particle Characterization

Particle characterization involves the analysis of physical and chemical properties of particles, such as size, shape, surface charge, and composition. The script mentions various techniques used for characterizing nanoparticles, including size exclusion chromatography, which helps understand the composition and purity of the nanoparticles. This is essential for ensuring the quality and consistency of nanomedicine formulations.

💡Biological Characterization

Biological characterization pertains to the study of how nanoparticles interact with biological systems, including cell uptake, tissue distribution, and potential toxicity. The script refers to collaborations with other teams to obtain biological data on the nanoparticles they formulate, which is critical for assessing the safety and efficacy of nanomedicines.

💡Regulatory Challenges

Regulatory challenges in nanomedicine involve the complexities of obtaining approval for new nanoformulations due to the novelty of the technology and the need for rigorous safety and efficacy testing. The script touches on the difficulties faced in navigating regulatory pathways for nanomedicines, which is a significant hurdle in bringing these innovations to market.

💡Ocular Application

Ocular application refers to the use of drugs or therapies in the eye. The script discusses a project focused on ocular applications for nanomedicines, specifically for the treatment of retinitis pigmentosa, a disease that leads to blindness. The use of nanoparticles in ocular applications can improve the delivery of therapeutics to the eye, enhancing treatment outcomes.

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