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Synthesis of customized Nanoparticles for biomedical Applications

Compressed fluid-based technology platform for biomaterials processing
Compressed fluid-based technology platform for biomaterials processing

Scientific leaders: Prof. Nora Ventosa & Prof. Jaume Veciana
Coordinators: Dr Gemma Martinez and Dr. Nathaly Segovia

Industrial problem/gap covered

The conventional approaches used for the production of particulate molecular biomaterials usually follow easy preparation methods at the laboratory scale, but they fail when scaling-up to industrial level.

Description

NANBIOSIS approach offers novel synthetic strategies and experimental setup for the advanced preparation of a wide range of nanoparticles, including inorganic and soft nanoparticles with biomedical application. An example is CF-based methodology which presents several advantages including the reduction of organic solvent use, low working temperatures, few operational steps and easy scale-up for the preparation of uniformly structured materials with precise and reproducible structural characteristics at micro-, nano- and supramolecular levels. Furthermore, CF-based methods have been shown to be suitable processes for the one-step preparation of polymeric micro- and nanoparticles and nanovesicles for the delivery of therapeutic entities with increased bioavailability, efficacy, stability and selectivity.

In the development of this biomedical solution, the following services are involved:

Nanovesicles like Quatsomes

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U6 Nanovesicles like Quatsomes  

 

– Nanovesicular systems composed by sterols and cationic surfactants.
– Size in the nano-range (below 100nm) – Uniform shapes (spherical and unilamellar)
– Highly Monodisperse
– Long-term stability (up to one year)
– Antimicrobial and antifungal properties

 

– Drug Delivery Systems (DDS) for both pharmaceuticals (Active pharmaceutical ingredients (APIs), etc.) and biopharmaceuticals (proteins, DNA, RNAs, etc.)
– Entrapment of dyes, stabilizing and targeting moieties.

 

Ref:

 

1. New nanodrug improves the treatment of diabetic foot ulcers (http://www.dicat.csic.es/rdcsic/index.php/en/biologia-y-biomedicina-2/108-histories-d-exit/310-una-nanomedicina-mejora-la-regeneracion-de-las-ulceras-de-pie-diabetico), Patent WO 2014/019555 A1.
2. Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents, Nano Letters, DOI: 10.1021/nl4017072.

Nanovesicles like Liposomes

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U6 Nanovesicles like Liposomes  

 

– Nanovesicular systems composed by sterols and phospholipids
– Size in the nano range (below 200nm)
– Monodisperse
– Uniform shapes (spherical and unilamellars)
– Short-term stability (1 month)

 

– DDS for both pharmaceuticals and biopharmaceuticals.
– Entrapment of dyes, stabilizing and targeting moieties.

 

Ref:

 

1. Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents, Nano Letters, DOI: 10.1021/nl4017072.

PEGylated Nanovesicles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U6 PEGylated Nanovesicles  

 

– PEGylated nanovesicular systems
– Size in the nano range (below 100 nm)
– Highly Monodisperse
– High Uniform shapes (spherical and unilamellar)
– Long term stability (up to one year)

 

– DDS for both pharmaceuticals and biopharmaceuticals, with high stability due to the functionalization with hydrophilic poly (ethylene glycol) (PEG), a stealth agent used to prolong blood-circulation time while reducing mononuclear phagocyte system uptake.
– Entrapment of dyes and targeting moieties.

 

Ref:

 

1. Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents, Nano Letters, DOI: 10.1021/nl4017072

Polymeric particles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U6 Polymeric particles  

 

– Polymeric Nanoparticles composed by biocompatibles polymers, such as PVP, GANTREZ, EUDRAGIT, PEG, CYCLODEXTRINES.
– Size in the micro, submicron, and nano range
– Monodisperse
– Uniform shapes

 

-DDS for both pharmaceuticals (APIs, anticancer drugs,etc.)

 

Ref:

 

1. High Loading of Gentamicin in Bioadhesive PVM/MA Nanostructured Microparticles Using Compressed Carbon-Dioxide, Pharm Res (2011), DOI: 10.1007/s11095-010-0248-x
2. Novel bioactive hydrophobic gentamicin carriers for the treatment of intracellular bacterial infections, ActaBiomaterialia (2011), DOI:10.1016/j.actbio.2010.11.031

Solid fine particles of APIs

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U6 Solid fine particles of APIs  

 

– Fine particles of APIs
– Size in the micro range
– Narrow size distribution
– High crystallinity degree
– High polymorphic purity
– Free of residual solvents

 

– To increase the bioavailability and dissolution rate of pharmaceuticals
– To allow the use of a more appropriate and/or convenient administration route, such as subcutaneous, intramuscular, topical and intestinal modes of administration

 

Ref:

 

1. Crystallization of Microparticulate Pure Polymorphs of Active Pharmaceutical Ingredients Using CO2-Expanded Solvents, Cryst. Growth Des. (2012), DOI: 10.1021/cg200356x

Hollow Au Nanoparticles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Hollow Au Nanoparticles  

 

Gold nanoparticles with spherical shape and average diameters ranged between 60-80 nm

 

Application: Photothermal therapy and thermally induced gene expression

 

Ref:

 

– RSC Adv., 2016,6, 58723-58732.
– Biomaterials, Volume 35, Issue 28, September 2014, Pages 8134-8143
– Nanomedicine: Nanotechnology, Biology and Medicine, Volume 9, Issue 5, July 2013, Pages 646-656

Au Magnetic /SiO2nanoshellwith a spions located inside

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Au Magnetic /SiO2nanoshellwith a spions located inside  

 

Magnetic nanoparticles in the core, covered by a shell of SiO2 with an external layer of gold, and average diameter of 100 nm

 

Application: Photothermal therapy and MRI signaling (theranosticnanoparticles)

 

Ref:

 

– Nanoscale. 2014 Aug 7;6(15):9230-40.

Hollow Au nanoshell with a spion located inside

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Hollow Au nanoshell with a spion located inside  

 

Magnetic Gold-based nanoparticles with magnetic and optical properties. Spherical shape and average diameter of 150 nm

 

Application: Photothermal therapy and MRI signaling (theranostic nanoparticles)

 

Ref:

 

– Nanoscale. 2014 Aug 7;6(15):9230-40.

Au NPs capped with citrate

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Au NPs capped with citrate  

 

Gold nanoparticles with average diameters of 20 nm

 

Application: Transfection reagent

 

Ref:

 

– ActaBiomaterialia, Volume 7, Issue 10, October 2011, Pages 3645-3655

Au nanorods capped with lysine

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Au nanorods capped with lysine  

 

Gold-based nanorods

 

Application: Contrast agents for optical coherence tomography

 

Ref:

 

– ChemCommun (Camb). 2012 Jul 7; 48(53): 6654–6656

Au nanorods capped with citrate

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Au nanorods capped with citrate  

 

Gold-based nanorods

 

Application: Photothermal therapy

 

Ref:

 

– Materials Research Bulletin, Volume 48, Issue 10, October 2013, Pages 4051-4057

CuS nanoparticles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 CuS nanoparticles  

 

Copper sulfide nanoparticles with an average diameter of 150 nm

 

Application: Photothermal therapy

 

Ref:

 

– ACS Appl Mater Interfaces. 2016 Aug 24;8(33):21545-54.

Hollow CuS nanoparticles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Hollow CuS nanoparticles  

 

Sulphur/copper hollow nanoparticles with an average diameter of 200 nm

 

Application: Photothermal therapy

 

Ref:

 

– ACS Appl Mater Interfaces. 2016 Aug 24;8(33):21545-54.

Carbon nanodots

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Carbon nanodots  

Carbon-based nanoparticles with spherical shape and average diameters ranged between 2-6 nm

 

Application: Bioimaging in the UV-Vis-Near Infrared ranges

 

Ref:

 

Chem. Eur. J. 10.1002/chem.201604216

Magnetic nanoparticles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Magnetic nanoparticles  

 

Iron-based nanoparticles with spherical shape and average diameters ranged between 6 -13 nm

 

Application: MRI diagnosis (T2 contrast agents)

 

Ref:

 

J Nanopart Res (2014) 16:2292

PLGA nanoparticles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 PLGA nanoparticles  

 

Application: drug delivery

 

Ref:

 

– ActaBiomater. 2017 Mar 1;50:493-501.
– RSC Adv., 2016,6, 111060-111069

Polymeric nanoparticles with an Au nanoparticles inside

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U9 Polymeric nanoparticles with an Au nanoparticles inside  

 

Application: Drug delivery and contrast agents (theranostics)

 

Ref:

 

Nanoscale, 2016,8, 6495-6506

Peptide-targeted Nanovesicles

Unit Type of NP Specifications of the NP (Size, composition, etc) Applications & reference
U6 with collaboration of U3 Peptide-targeted Nanovesicles  

 

– Nanovesicular systems composed by sterols and phospholipids
– Size in the nano range (below 200nm)
– Monodisperse
– Uniform shapes (spherical and unilamellar)
– Short-term stability (2 months)

 

– DDS for both pharmaceuticals and biopharmaceuticals, with high stability due to the functionalization with an RGD targeting peptide. – “Active targeting” through the incorporation of specific molecules on the outer surface of nanovesicles, which can provide more effective therapeutic action to a nanomedicine, due to a more specific and effective cellular uptake.

 

Ref:

 

1. α-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration, Nano Lett., 2013, DOI: 10.1002/adhm.201500746

 

It gathers several laboratories, perfectly equipped, to perform the mission of this facility: the development, characterization, and large-scale production of molecular biomaterials of therapeutic or biomedical interest, with controlled micro-, nano- and supramolecular structure. One example of Key-Enabling-Technology (KET) available in this unit is a simple one-step methodology, DELOS-SUSP, based on the use of compressed fluids (CF), such as CO2, to prepare particulate materials with precise and reproducible structural characteristics at micro-, nano- and supramolecular levels (size, shape, internal structural gradients, supra­molecular organization and crystalline purity).This example shows one of the singularities of this unit is that counts with CF–based plants at different scales, from mL to L, which allow process development by QbD and process scale-up.

 

This unit offers novel synthetic strategies and experimental setup for the advanced preparation of a wide range of nanoparticles, including inorganic and soft nanoparticles with biomedical application.

The new methodologies include microreactors, laser pyrolysis reactor and electro spinning. Both laser pyrolysis and microreactors as belonging to the group of enabling technologies, which allow new goals in reproducibility and scale-up production of nanomaterials. As for the electro spinning, this is a new infrastructure that allows the preparation of nanowires and fibres, formed by different materials.