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July 05-06, 2019 | Paris, France
Pharmaceutics and Advanced Drug Delivery Systems
2
nd
International Conference and Exhibition on
Asian Journal of Biomedical and Pharmaceutical Sciences | ISSN:2249-622X | Volume 9
Methacrylated chitosan with improved mucoadhesiveness for transmucosal
application
Oluwadamilola Kolawole
1
, Wing-Man Lau
2
and
Vitaliy Khutoryanskiy
1
1
University of Reading, UK
2
University of Newcastle, UK
Background:
The continued relevance and biomedical
application of chitosan are due to its safety and
mucoadhesiveness. Mucoadhesive delivery systems are
desirable to extend the bladder residence time of loaded
drugs. In recent years, maleimide and acrylate-functionalised
delivery systems are being explored for transmucosal
application due to their superior mucoadhesive features
relative to thiolated drug carriers. Methacrylated drug carriers
have not been explored for enhanced mucoadhesiveness. In
this work we have synthesised methacrylated chitosan with
a variable degree of modification (LMeCHI and HMeCHI) and
evaluated their pH sensitivity, mucoadhesiveness, and safety
in comparison to chitosan (CHI), for intravesical use.
Methods:
Products were characterised using 1H Nuclear
Magnetic Resonance (1H NMR), Fourier Transform- Infrared
and UV-Vis spectroscopy. 1H NMR and ninhydrin test
quantified the methacrylate grafting density on chitosan.
Turbidimetric analysis of samples evaluated their resistance
to pH changes in the biological fluid. The mucoadhesiveness
of fluorescein sodium in the presence of the mucoadhesive
polymers was evaluated using artificial urine flow-through
techniques and fluorescence microscopy. MTT assay was
used to study their UMUC3 malignant cell antiproliferative
features.
Results:
There was a broad correlation in the methacrylation
extent of LMeCHI and HMeCHI obtained with both methods.
Turbidimetric analysis (λ = 400 nm) revealed that the turbidity
of HMeCHI solution remained unchanged from pH 3 to 9
while that of CHI and LMeCHI increased rapidly after pH 6,
inferring that the stability of the drug carriers in biological
fluid may be improved by methacrylation. The degree of
methacrylate conjugation had a profound influence on their
mucoadhesiveness. The polymers are presented in order
of increasing mucoadhesion: FITC-Dextran < FS/CHI< FS/
LMeCHI < FS/HMeCHI. Based on MTT assay, the UMUC3
cell antiproliferative effect of the unmodified and modified
chitosan solutions (6.25-200 µg mL-1) was not significantly
different, confirming the biocompatibility of our novel
mucoadhesive polymers. Methacrylation of chitosan did not
compromise its biocompatibility with bladder cancer cells.
Conclusions:
Methacrylated chitosan is a safe drug carrier
for intravesical delivery with superior mucoadhesiveness
relative to chitosan. This result suggested that the degree of
methacrylation can be tailored for desirable physicochemical
properties of methacrylated chitosan. HMeCHI appears the
most promising for intravesical delivery of bladder cancer
chemotherapeutics
e
:
o.m.kolawoleneealuko@pgr.reading.ac.ukAsian J Biomed Pharmaceut Sci, | ISSN: 2249-622X
Volume 9