This document summarizes a presentation about polysaccharide hydrogels and their applications. It discusses how polysaccharides can be used to form hydrogels through various methods like ionotropic gelation or chemical cross-linking. It then outlines several biomedical applications of polysaccharide hydrogels, including for drug and protein delivery, tissue engineering, dental applications, and heritage protection. The document also discusses using polysaccharide nanohydrogels for controlled drug delivery and how they can be loaded with various drugs and biological agents.
Hydrogels are three-dimensional network of hydrophilic cross-linked polymer that do not dissolve but can swell in water or can respond to the fluctuations of the environmental stimuli
Hydrogels are highly absorbent (they can contain over 90% water) natural or synthetic polymeric networks
Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content
The chemical contamination of water from a wide range of toxic derivatives, in particular heavy metals, aromatic molecules and dyes, is a serious environmental problem owing to their potential human toxicity. Therefore, there is a need to develop technologies that can remove toxic pollutants found in wastewaters .Among all the treatments proposed, adsorption is one of the more popular methods for the removal of pollutants from the wastewater..
this ppt is about hydrogel.A hydrogel is a three-dimensional(3D) network of hydrophilic polymers that can swell in water and hold a large amount of water while maintaining the structure due to chemical or physical cross-linking of individual polymer chains. applications Flexibility of hydrogels, which is because of their water content, makes it possible to use them in different condition ranging from industrial to biological fields
Hydrogels are three-dimensional network of hydrophilic cross-linked polymer that do not dissolve but can swell in water or can respond to the fluctuations of the environmental stimuli
Hydrogels are highly absorbent (they can contain over 90% water) natural or synthetic polymeric networks
Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content
The chemical contamination of water from a wide range of toxic derivatives, in particular heavy metals, aromatic molecules and dyes, is a serious environmental problem owing to their potential human toxicity. Therefore, there is a need to develop technologies that can remove toxic pollutants found in wastewaters .Among all the treatments proposed, adsorption is one of the more popular methods for the removal of pollutants from the wastewater..
this ppt is about hydrogel.A hydrogel is a three-dimensional(3D) network of hydrophilic polymers that can swell in water and hold a large amount of water while maintaining the structure due to chemical or physical cross-linking of individual polymer chains. applications Flexibility of hydrogels, which is because of their water content, makes it possible to use them in different condition ranging from industrial to biological fields
Hydrogels are cross-linked, three dimensional, hydrophilic polymeric networks with the ability to hold large amount of water within its porous structure.
Presentation by Juliëtte van den Dolder from Noviocell; From technology to business. During SMB meeting on December 15, 2016 at SMB Life Sciences / Novio Tech Campus in Nijmegen, NL.
Hydrogels are cross-linked, three dimensional, hydrophilic polymeric networks with the ability to hold large amount of water within its porous structure.
Presentation by Juliëtte van den Dolder from Noviocell; From technology to business. During SMB meeting on December 15, 2016 at SMB Life Sciences / Novio Tech Campus in Nijmegen, NL.
Dr. Robert Langer - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
This presentaion is a short introduction into the fascinating subject of biocompatible packaging of MEMS / micro systems. I gave this presentation for a technology cluster of Dutch micro systems companies
Plenary lecture of the XVIII B-MRS Meeting given by Prof. Alan Taub (University of Michigan, USA) on September 26, 2019 at Balneário Camboriú (Brazil).
Plenary lecture of the XVIII B-MRS Meeting given by Prof. Antonio José Roque da Silva (CNPEM, Brazil) on September 24, 2019 at Balneário Camboriú (Brazil).
Tribute in honor of Prof. Ivo Alexander Hümmelgen, a member of the Brazilian materials research community, who died unexpectedly in March 2019. The tribute was made by Prof. Marco Cremona (PUC-Rio), on September 23, 2019 in Balneário Camboriú (Brazil), at the opening of symposium F, that was dedicated to Organic Electronics, the research area of Prof. Hümmelgen.
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Memorial lecture "Joaquim da Costa Ribeiro" given by Prof. João A. H. da Jornada (IF-UFRGS) on September 10, 2017 in Gramado (Brazil) during the opening of the XVI B-MRS Meeting.
Plenary lecture given by Prof. Kenneth Gonsalves (ITT Mandi, India) on September 12, 2017 in Gramado (Brazil) during the XVI B-MRS Meeting. Acknowledgment: ITT Mandi.
Plenary lecture given by Prof. Katsuhiko Ariga (WPI-MANA, NIMS and University of Tokyo, Japan) on September 12, 2017 in Gramado (Brazil) during the XVI B-MRS Meeting.
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Polysaccharide Hydrogels: a versatile tool for biomedical and pharmaceutical applications.
1. Polysaccharide hydrogels: a versatile tool
for biomedical and pharmaceutical
applications
Department of Drug Chemistry and Technologies
Sapienza University of Rome
Rome, Italy
Pietro Matricardi
XVII Brazil
MRS Meeting
September,16th -20th, 2018
Natal
7. The colloid condition, the gel, is one which is easier to
recognize than to define
Dorothy Jordan Lloyd (1926)
Or, in other words, “if it looks Jello, it must be a gel”
What is a hydrogel
8. • Like a “fourth state” of matter
ü polymer network (10-20%) and water
ü the concepts of solute and solvent from a “classical”
thermodynamic point of view are unable to describe the system
• Depending on its nature:
ü self sustaining under its own weight
ü able to shear under the action of a stress
Some characteristics
10. 10
From a rheological point of view
(Ross-Murphy and Burchard):
viscoelastic behaviour
Solution
Strong gel
Weak gel
11. Polysaccharides
ü Most of them are abundant in nature (commodities or mass-market
products)
ü Readily available from renewable sources (algal and plant kingdoms,
cultures of microbial selected strains, recombinant DNA techniques)
ü Large variety of compositions and properties
ü Biocompatible (food, medical device or pharma applications)
ü Often cheaper than synthetic polymers
ü Favourable chemical and physico-chemical properties due to the wide
variety of functional groups, macromolecular architecture and molecular
weights
13. As “inert” drug carrier in conventional formulations:
• Filler (bulk formulation)
• Film forming (tablets or capsules)
• Viscosity agent in liquid formulations
20. HYDROGEL FOR DENTAL APPLICATIONS
üComplete filling of confinedspaces, such as gum pockets
üAble to carry
q Drugs
q Biologically Active Substances
üThe gel adheres to soft tissues due to the film-formingproperties
of one of the polymer component
üObtained by means of ionotropic gelation so no chemical
reactionsare involved nor toxic substances are formed as
byproducts
22. To improve bone growth for implant
On the market
Ø Homologous bone - animal derived products - synthetic
bone
Ø Osteocompatible resins
Pilot study #1 - Hydroxyapatite
23. ü Treatement of severe periodontitis
ü Cleaning of the pocket by curette
ü Applications of the drug loaded-hydrogel
ü New implant after 8 weeks
Pilot study #2 - nimesulide
NB
BM
n-MT
NB
NB
n-MT
BM
NB
Ematossilina-Eosina 4X
% n-MT (non-Mineralized Tissue): 65%
% BM (Biomaterial): 5%
% NB (New Bone): 30%
24. üFilling effect
üPain relief (with and without drug) in all
patiences
üHydrogel resorption in 4 weeks and
promotion of new bone formation
Results
26. ü Cleaning and protection of stone materials
ü Bio-colonization
ü Organic solvent-free product
Why polysaccharide hydrogels
Italy possesses a huge heritage
(45% of the world cultural heritage?!?!?)
31. Drug Delivery – Controlled release
Polymeric nanoparticle
Liposome
dendrimer
Inorganic nanoparticle
“MAGIC BULLET”
A substance or therapy capable of destroying pathogenic agents
(as bacteria or cancer cells) or providing a remedy for a disease
or condition without deleterious side effects, by specifically
targeting the diseased tissue
Dr. Paul Ehrlich
Solid Lipid Nanoparticle
Nanogels
Nanoscale hydrogels
32. POLYSACCHARIDE-BASED NANOHYDROGELS
SELF-ASSEMBLING
IN WATER
HYDROPHOBIC MOIETY
POLYSACCHARIDE
ü Nanosized hydrogels (150-300 nm)
ü Nanoparticulate drug carriers
ü High water content
ü High biocompatibility
ü Mucoadhesive properties
gellan gum
or
hyaluronan
prednisolone
cholesterol
riboflavin derivatives
34. (121°C, 1.10 bar, 20 min)
1) preparation of
sterile NHs
2) Reduction of the NHs
polydispersity
3) Simultaneous formation, loading*
and sterilization of NHs
HYDROPHOBIC MOIETY
POLYSACCHARIDE
Autoclave treatment *
* new patented method:
• WO2014199318 (A2) ― 2014-12-18 MC De Rugeriis, E. Montanari, C. Di Meo, P. Matricardi - METHOD FOR PREPARING NANOHYDROGELS
• WO2014199319 (A2) ― 2014-12-18 G. D’Arrigo, C. Cencetti, C. Di Meo, P. Matricardi - METHOD FOR THE TREATMENT OF NANOHYDROGELS
An innovative method for sterile polysaccharide NHs production
Cryo -TEM
100 nm
Autoclave
121°C
1.10 bar, 20 min
* For thermo-stable drugs
polymerdrug
Co-suspension in water Film-casting technique
drug film
polymer suspension
35. Long-term storage
0
50
100
150
NHs before freeze-
drying
NHs + dextrose
before freeze-drying
NHs + dextrose after
freeze-drying
d (nm)
0
0.2
0.4
0.6
0.8
1
PDI
diameter PDI
E. Montanari, M.C. De Rugeriis, C. Di Meo, R. Censi, T. Coviello, F. Alhaique, P. Matricardi Journal of Materials Science: Materials in Medicine , 2015,26:32
Freeze-drying
36. HACH
HARfv
NHs self assembly
~ 200 - 300 nm
(hydrophobic interactions)
Autoclave
20 min 121 °C
CAC = 134 µg/mL
scattering intensity
mean size
scattering intensity
mean size
CAC = 235 µg/mL
NHs properties
42. Advantages:
ü Prednisolone is already clinically used in combination with chemotherapeutics in
several anticancer protocols (e.g. prostate cancer) to prevent or reduce side
effects.
ü Inflammation contributes to tumor initiation, induces proliferation of malignant
cells, enhances their survival, and stimulates angiogenesis and metastatic spread.
ü Cancer, in turn, takes advantage of inflammatory mediators to grow, thereby
generating an inflammatory microenvironment in tumors for which there is no
underlying inflammatory condition.
Paclitaxel (PCT)
Prednisolone
43. Mw reduction
by Ultrasonication
Sonication time
Mw/Mn
Sonication time1
3
2
4
5
1
3
2
4
5
1
3
2
4
5
1
32
4
5
6 6’
6 6’
-CH3
1.40 1.30 1.20
18
20
22
ppm
Gellan Gum
Glc Glc haGlc
GPC
ü Mw reduction of gellan by probe ultrasonication
1
H-13
C HSQC NMR map
44. ü Synthesis of polymer derivatives
Same steps with cholesterol (dd = 10%)
derivatization degree (dd) = 10% m/m
yield = 50%
ü NHs formation and stability
PREDNISOLONE or CHOLESTEROL
GELLAN GUM
nanoprecipitation ultrasound treatment
or
25°C
45. ü Cell biocompatibility
G. D'Arrigo, C. Di Meo, E. Gaucci, S. Chichiarelli, T. Coviello, D. Capitani, F. Alhaique, P. Matricardi Soft Matter 2012, 8, 11557
Fibroblast
Heart myoblast
Prostate cancer
47. • Paclitaxel loading into Ge-pred and Ge-CH NHs by
solvent casting technique
• Paclitaxel concentration reached in NHs suspension =
140 µg/mL (free Paclitaxel in water = 0.1 µg/mL)
Paclitaxel (PCT)
Prednisolone
ü Loading with anticancer drug
PCT release in vitro
PC-3 cells, 72h
PCT 3 nM
48. IC50
Paclitaxel: 33.7 nM
Paclitaxel in NHs: 15.1 nM
Paclitaxel in NHs + Prednisolone: 7.7 nM
G. D'Arrigo, G. Navarro, C. Di Meo, P. Matricardi, V. Torchilin, European Journal of Pharmaceutics and Biopharmaceutics 2014, 87, 208
Skov-3 cell line
Anticancer activity of PCT-loaded NHs
53. • Antibiotic resistance due to the intracellular escape (for
facultative or obligate pathogens)
• Levofloxacine: poorly effective against intracellular bacteria
(efflux pump)
Levofloxacin
54. • Levofloxacin loading into HA-CH NHs by autoclave technique
• Levofloxacin concentration reached in NHs suspension = 12 ± 1 %
w/w
• Antibacterial activity against S. Aureus and P. Aeruginosa strains
• Cell (HeLa) infection by S. Aureus and P. Aeruginosa and treatment
with free LVF and LVF-loaded NHs
Levofloxacin
MIC values of Levoflloxacin (LVF) and NH-encapsulated
Levofloxacin (NH-LVF) on S. aureus ATCC6538P, S.aureus
USA300-0114 and P. aeruginosa PAO-1.
Comparable MIC
E. Montanari, G. D’Arrigo, C. Di Meo, A. Virga, T. Coviello, C. Passariello, P. Matricardi. Eur. J. of Pharmaceutics and Biopharmaceutics, 2014, 87, 518
55. FREE LVF: no significant activity
on intracellular bacteria
Activity of LVF and NH-LVF (both freshly prepared and resuspended
after freeze-drying) on intracellular P. aeruginosa PAO-1 and S.
aureus USA 300-0114.
LVF-NHs: > 90% eradication
of intracellular bacteria
57. • Levofloxacin (LVF) and gentamicin(GM) loading into HA-CH NHs
• Antiibacterial activity against S. Aureus
• Human keratinocites (HaCaT) infection by S. Aureus and treatment
with free LVF and GM drug-loaded NHs
58. Scheme of the intracellular fate of free GM, LVF and their nanoformulations in
S. aureus-infected keratinocytes.
E. Montanari, A.Oates, C. Di Meo, J. Meade, R. Cerrone, A. Francioso, S. Devine, T. Coviello, P. Mancini, L. Mosca and P. Matricardi Adv. Healthcare Mater. 2018, 1701483
60. Topical applications of NHs -1
Piroxicam
Ge-CH
Ge-Rfv
U.M. Musazzi, C. Cencetti, S. Franzé, N. Zoratto, C. Di Meo, P. Procacci, P. Matricardi, F. Cilurzo, Mol. Pharmaceutics 2018, 15, 1028−1036
61. Baicalin
Ge-CH
M. Manconi, M.L. Manca C. Caddeo, C. Cencetti, C. Di Meo, N. Zoratto, .. P. Matricardi Eur. J. Pharm. Biopharm. 2018, 127, 244–249
Topical applications of NHs -2
62. Other applications
ü NHs in aesthetic surgery
ü Antioxidant for cardiovascular applications
ü Anti-inflammatory-loaded NHs for the treatment of primary
sclerosing cholangitis
ü NHs formulations for ocular applications
ü HA-based NHs in cosmetics