Universidade de São Paulo

http://www5.usp.br/

Instituto de Química de São Carlos

www.iqsc.usp.br

MODIFICAÇÕES QUÍMICAS E CARACTERIZAÇÃO DE BIOPOLÍMEROS

Local: Universidad Nacional de Ingeniería –Lima/Peru

Período: 28/11 – 07/12/2016

Responsável: Prof. Dr. Sérgio Paulo Campana Filho (scampana@iqsc.usp.br)

Instituto de Química de São Carlos da Universidade de São Paulo (IQSC/USP – Brasil)
Aplicações biomédicas e farmacêuticas de quitosana
Fundamentos e Perspectivas
 CURRENT MAJOR CHALLENGES IN
NANOMEDICINE AND PHARMACEUTICS

• Effective non-viral gene delivery to mammalian cells

→ gene therapy

• Transport of therapeutic biomacromolecules across mucosal

epithelia (oral, nasal, ocullar, pulmonary)
→ needle free therapies (e.g. insulin, vaccines)

• Strategies that avoid antimicrobial resistance

→ antibiotics free therapies

• Effective active targeting to cancer cells

• Transport of low permeable drugs across the blood to brain

barrier
CHITOSAN APPLICATIONS IN PHARMACEUTICS
CHITOSAN-BASED NANOCARRIERS FOR IN VIVO
TRANSMUCOSAL ADMINISTRATION OF
BIOACTIVE MACROMOLECULES

Alonso et al. (2007) In: Nanoparticles for Pharmaceutical Applications.

Edited by J. Domb, Y. Tabata, M. N. V. Ravi Kumar, and S. Farber.
American Sci. Pub. pp 135–150
Chitosan-Based Microparticles and Nanoparticles
Biopharmaceuticals

• Water-in-Oil Emulsion and Chemical Cross-linking

• Ionic Cross-linking
• Spray Drying
• Supercritical Fluid Drying
• Electrospraying
• Coacervation and Precipitation
• DNA–Chitosan Interaction
• siRNA–Chitosan Interaction
Chitosan-Based Microparticles and Nanoparticles
Biopharmaceuticals
 Chitosan-based BIOnanomaterials
Chitin-nanofibers

Matrix-
Polymer-based

nanospheres
CS-hybrid
dendrimers Chitosan
CS-amphiphilic nanoscaffolds
micelles
Surface functionalization

CS-coated
liposomes

CS-coated
nanocapsules

CS-coated solid-lipid
nanoparticles
CS-coated
metalic NPs

CS-functionalized
carbon nanotubes
 A MODEL FOR THE INTERACTION
NANOPARTICLES/EPITHELIUM

Tight junctions

Systemic absorption

Loaded nanoparticles
Active (e.g. insulin)

Teijeiro-Osorio et al. (2009) Biomacromolecules, 10, 243–249

IONIC CROSSLINKED CHITOSAN NANOPARTICLES

Dilute chitosan solution (C < C*) TPP-crosslinked chitosan nanoparticles

+
+ +
+ + + +
+ +
+ +
+
+ +
+ +
Pentasodium +
tripolyphosphate ions ++
+ +
(TPP) (P3O5–10 ) +
+ +
+ + +
+ +
+ +

C* .- critical overlap concentration Diameter range ~ 100 – 400 nm

Zeta potential ~ +40 – 55 mV
EFFECT OF DA&PA& M ON THE AVERAGE DIMENSIONS
OF TTP-CROSSLINKED CHITOSAN NANOPARTICLES

500 +45
LDP CS
+40
400 HDP CS

Zeta potential (mV)

+35
300
Size (nm)

+30
200
+25
100 Low DP
+20
High DP
0 +15
0 10 20 30 40 50 60 0 10 20 30 40 50 60
Degree of acetylation (%) Degree of acetylation (%)
EFFECT OF DA&PA& M ON THE AVERAGE DIMENSIONS
OF TTP-CROSSLINKED CHITOSAN NANOPARTICLES

DA 0 – 20% GlcN (D)

GlcNAC (A)

TPP

DA > 20% N-acetylated chitosan favors the formation

of “loops” and increases the particles’ size
GENIPIN CROSSLINKLING: MEAN SIZE AND ZETA
POTENTIAL OF CS-TPP NANOPARTICLES

1400 +50

+45
1200
+40

1000 +35

Zeta potential (mV)

+30
800
Size (nm)

+25
600
+20

400 +15

+10
200
+5

0 +0
- - -- HA NP - - -- HA NP
PP P - 7006 GNP - 6009 GNP PP P - 7006 GNP - 6009 GNP
S -T P-GN 6- 9-
- G
CS HA- S -T P-GN 6- 9-
- G
CS HA-
G G G G
C TP
- -AL -700 -AL -600 - C TP
- -AL -700 -AL -600 -
CS CS ALG CS ALG CS CS CS ALG CS ALG CS
S- - - -
C CS C S CS
 FINAL REMARKS & PERSPECTIVES

 Development of better suited methods to produce and fully characterize

chitosan and its derivatives, including polyelectrolytes, amphiphilic and
cross-linked derivatives
 Strategies to modify the surface of chitosan-based nanoparticles to
achieve specific functions: drug targeting, antibacterial effects, allergy
therapies
 Mucoadhesive chitosan-based nanocarrier platforms for transmucosal
delivery (bucal, stomach, vagina)
 Development of innovative tools and approaches for a better
understanding of the fate and degradation (in vitro and in vivo) of
chitosan-based nanoparticles and biomaterials
 Better understanding of the behaviour of “soft” nanobiomaterials in vitro
and in vivo by using knowlegde gained on physical models for
nanomaterials
 Development of novel nanotechnological strategies for overcoming the
blood-to-brain barrier
DERIVADOS DE QUITINA E QUITOSANA