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Antonio Di Martino
Study of pH and thermo-responsive properties of nanoparticles based on an amphiphilic co-polymer
Centrum Polymerních Systemů Fakulta Technologická
Univerzita Tomáše Bati ve Zlíne
Studium pH a tepelně citlivých vlastností nanočástic založených na amfofilních kopolymerech
Stimuli-Responsive Polymers (SRP): Definition
SRP are systems that may overcome properties changes responding to variations of
pH
Temperature
Ionic Strength
Light
Magnetic field
Electric field
SRP : Biomedical Applications
Drug Delivery
Gene Therapy
Cancer Targeted Therapy
Diagnostic (Glucose Detection)
Regenerative Medicine
Particular interest in polymers sensitive to
pH
Temperature
SRP : pH Responsive Polymers
Polyelectrolytes
PMAAPDMAEMA
Polybases Polyacids
PEI
PLL
Chitosan
PSA
Alginic Acid
Biological Responsive Hybrid Biomaterials- E.Jabbari and A.Khademhosseini
SRP : Temperature Responsive Polymers
PNIPAM
LCST (Lower Critical Solution Temperature)
PVCL PDEAM LCST close to the human body temperature
UCST (Upper Critical Solution Temperature)
PAA UCST close to the human body temperature
Polymers with dual stimuli-responsiveness
Sensitive to both pH and temperature
Combination of thermo responsive polymers - polyelectrolytes
New generation of monomers
Some examples
ELPs - Elastine-Like-Polymers Obtained by Genetic Engineering
PDMAEM - Poly(N,N- DiMethylAminoEthylMethacrylate)
PAcrNPP - Poly( Acryloyl-N-PropylPiperazine)
PEPyM - Poly (N-EthylPyrrolidineMethacrylate)
CS-g-PLACA synthesis
Chitosan PLACA
CS-g-PLACA
Good biological properties
Poor mechanical properties
Good mechanical properties
Incompatibility with cells and blood
Low Molecular Weight Chitosan with Deacetylation Degree (DD) 75-85%
PLACA : up to 10 kDa
Polycondensation reactionMethanesulfonic acid160˚C
Coupling Reaction
Different amount of –COOH groups
CS-g-PLACA Dextran Sulfate
0.5 mg/mL in deionized H2O
1 mg/mL in CH3COOH pH 5.5
Stirring Room Temperature
SRP : CS-g-PLACA NPs - Preparation
Dimension
-potential
Morphology
FTIR-ATR
1H-NMR
Poly Electrolyte Complexation Method
SRP : CS-g-PLACA NPs
Effect of Temperature : range 5 – 60 ˚ C
Effect of pH : range 3.5 - 9
diameter-potential
Influence of PLACA side chain
Dynamic Light Scattering
Results : NPs diameter VS Temperature in acidic media
Each experiment was performed in triplicate, average values are reported with SD up to 10%
Tcr Tcr
Chitosan (CS) No temperature response
CS-g-PLACA 2%
CS-g-PLACA5%
Temperature response
Swell - Collapse
Results : NPs diameter VS Temperature in alkaline media
Each experiment was performed in triplicate, average values are reported with SD up to 10%
Increasing pH of the media
Less sensitivity
No Critical Temperature (Tcr)
Nanoparticles diameter is stable
Each experiment was performed in triplicate, average values are reported with SD up to 10%
Results : NPs -potential VS Temperature in acidic media
Chitosan (CS)
CS-g-PLACA2%
CS-g-PLACA5%
No temperature response
-pot. values switch from positive to negative
pI around 50˚C
Each experiment was performed in triplicate, average values are reported with SD up to 10%
Results : NPs -potential VS Temperature in alkaline media
Increasing pH of the media
Less sensitivity
No pI at pH 9
CS-g-PLACA NPs Applications
Responsive Drug Delivery System
Gene Therapy
Conclusions
An amphiphilic co-polymer was synthetized by grafting carboxyl-functionalized polylactide to chitosan backbone ( CS-g-PLACA)
Polymeric nanoparticles were obtained via Poly Electrolytes Complexation (PEC) method at room temperature in a solvent free media
CS-g-PLACA nanoparticles show temperature responsive properties (swelling-collapse)
The % of swelling is related to the pH of the media
Possibility to shift -potential value from positive to negative by warming the system
Thank you for your attention
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Grazie per l’attenzione
