Background: Development of pH-responsive nanoparticles capable of rapid degradation in
the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in
the physiological pH (pH 7.4) is desirable.
Objective: To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate
acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the
drug loaded into the nanoparticles.
Method: Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C
NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by
free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers
and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH
7.4. The statisitical experimental design was randomized complete block design followed by analyses of
variance with F-test of significance. Pairwise comparison test was used to locate specific differences
among parameters of the crosslinkers and the nanopaticles.
Results: Scanning electron micrographs showed the formation of spherical particles. Particle size analysis
showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed
that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and
drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)-
[2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2-
methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl]
Conclusion: The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially