Date post: | 10-Jun-2015 |
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EFFECT OF POLYLACTIDE MOLECULAR WEIGHT ON DOXORUBICIN AND TEMOZOLOMIDE RELEASE FROM CHITOSAN-GRAFTED POLYLACTIDE NANOPARTICLES
Antonio Di Martino
Introduction
Drug Delivery
POLYMERS IN DRUG DELIVERY
Natural Synthetic
Chitosan
Low Immune Response
Biodegradability
Reactive groups
Introduction
Alginate
Biocompatibility
PEG
Gelatin PMMA
PLA
Co-polymer Synthesis
Chitosan Polylactide
CS-g-PLA
Good biological properties
Poor mechanical properties
Good mechanical properties
Incompatibility with cells and blood
Low Molecular Weight Chitosan with Deacetylation Degree (DD) 75-85%
Polylactide : 10 and 60 kDa Polycondensation reactionMethanesulfonic acid160˚C
Coupling Reaction
Ionotropic Gelation
CS-g-PLA Tripolyphosphate
1 mg/mL in PBS pH 7.4
1 mg/mL in CH3COOH pH 5.5
Stirring Room Temperature
Nanoparticles Preparation
Size-pot
Morphology
FTIR-ATR1H NMR
Morphology
Doxorubicin (DOX)
Temozolomide (TMZ)
Tripolyphosphate in PBS pH 7.4
DOX in CH3COOH(aq) pH 5.5
TMZ in CH3OH
CS-g-PLA in CH3COOH pH 3.5
• Size (nm)• -pot (%)• Encapsulation (%) • Release • TEM• Swelling Index
Encapsulation and Co-Encapsulation
Release Kinetic
T = 25˚C ; pH 3.5, 7.4 and 9
T = 37˚C ; pH 3.5, 7.4 and 9
Nanoparticles Preparation
Results: copolymer characterization
FTIR-ATR 1H-NMR
CS
CS-g-PLA
Tra
nsm
ittan
ce(%
)
1.3 and 1.4ppm methyl protons located at the terminal groups of the backbone
4.2 and 5.1 ppm terminal methenyl protons of the branched polylactide and repeats unit in the chain
1730 cm-1 carbonyl of ester bond
2100 cm-1 C-N strech more intense
Results : NPs characterizationCS-g-PLA 10kDa
CS-g-PLA 60kDa
pH 5.5
Results : NPs characterizationCS-g-PLA 10kDa
CS-g-PLA 60kDa
pH 7.4
Results : Encapsulation Efficiency
DOX TMZ pHPLA 10 kDa 53% 47% 3.5
42% 58% 7.4
64% 36% 9
PLA 60 kDa 54% 46% 3.5
41% 59% 7.4
55% 45% 9
100
t
ft
D
DDEE
• Dt = Total amount of drug (µg/mL)• Df = Amount of drug unloaded (µg/mL)
DOX Abs : 480 nm TMZ Abs : 325 nm
Encapsulation
Co-Encapsulation
Results: Swelling Index(SI)
100
d
ds
W
WWSI
Ws = average weight of swollen sample (g) Wd = average weight of dry samples (g)
Swelling properties influence Release Kinetic
Human Serum37˚C; 24h
CS
CS-g-PLA 10kDa
CS-g-PLA 60kDa
Results : Release Kinetic Buffer solutions : pH 3,5 -7.4-9 Temperature : 37 ˚C Moderate stirring : 400rpm
CS-g-PLA 10 kDa CS-g-PLA 60 kDa
1000
D
DDR
t Dt = amount of drug released at t time (µg)
D0 = amount of drug loaded (µg)
DOX Abs : 480 nm TMZ Abs : 325 nm
Results : Co-Release Kinetic
CS-g-PLA 10 kDa CS-g-PLA 60 kDa
Increasing pH of the medium the release rate rise
TMZ is released faster than DOX in CS-g-PLA 10kDa
CS-g-PLA 60kDa drugs are released almost simultaneously
Conclusions
Polylactide with different Mw was successfully grafted to chitosan backbone as confirmed by FTIR-ATR and 1H-NMR analysis
Size (150-350nm) and -potential (25-45mV) values indicate that nanoparticles own good stability in physiological like media at different temperature
CS-g-PLA show high encapsulation and co-encapsulation either acidic or neutral environment
Sustained release and co-release in physiological like environment (almost 2 weeks) in both formulations (CS-g-PLA 10kDa and CS-g-PLA 60kDa)
Modulation of the release rate modifying the pH of the medium
Thank you for your attention.