This document discusses stimuli-responsive polymers (SRP), specifically those responsive to pH and temperature. It summarizes various pH- and temperature-responsive polymers used in biomedical applications like drug delivery. It then describes the synthesis of an amphiphilic co-polymer called CS-g-PLACA by grafting carboxyl-functionalized polylactide to chitosan. Polymeric nanoparticles were formed from CS-g-PLACA using a solvent-free method and were found to be temperature responsive, swelling and collapsing depending on temperature and pH. The nanoparticles have potential applications as responsive drug delivery systems and in gene therapy.

1. 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
dimartino@ft.utb.cz
Studium pH a tepelně citlivých vlastností nanočástic
založených na amfofilních kopolymerech

2. 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

3. SRP : Biomedical Applications
 Drug Delivery
 Gene Therapy
 Cancer Targeted Therapy
 Diagnostic (Glucose Detection)
 Regenerative Medicine
 Particular interest in polymers sensitive to
 pH
 Temperature

4. SRP : pH Responsive Polymers
Polyelectrolytes
PMAA
PDMAEMA
Polybases Polyacids
PEI
PLL
Chitosan
PSA
Alginic Acid
Biological Responsive Hybrid Biomaterials- E.Jabbari and A.Khademhosseini

5. 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

6. 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)

7. 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 reaction
Methanesulfonic acid
160˚C
Coupling Reaction
Different amount of –COOH groups

8. 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
 ζ-potential
 Morphology
 FTIR-ATR
 1
H-NMR
Poly Electrolyte Complexation Method

9. SRP : CS-g-PLACA NPs
 Effect of Temperature : range 5 – 60 ˚ C
 Effect of pH : range 3.5 - 9
diameter
ζ-potential
 Influence of PLACA side chain
Dynamic Light Scattering

10. 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

11. 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

12. Each experiment was performed in triplicate, average values are reported with SD up to 10%
Results : NPs ζ-potential VS Temperature in acidic media
Chitosan (CS)
CS-g-PLACA2%
CS-g-PLACA5%
No temperature response
 ζ-pot. values switch
from positive to negative
 pI around 50˚C

13. Each experiment was performed in triplicate, average values are reported with SD up to 10%
Results : NPs ζ-potential VS Temperature in alkaline
media
 Increasing pH of the media
 Less sensitivity
 No pI at pH 9

14. CS-g-PLACA NPs Applications
 Responsive Drug Delivery System
 Gene Therapy

15. 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 ζ-potential value from positive to negative by warming the system

16. Thank you for your
attention
Děkuji za pozornost
Grazie per l’attenzione