| خلاصه مقاله | Alzheimers disease (AD) is a progressive and irreversible neurodegenerative disease. Many
neurodegenerative diseases require the efficient delivery of drugs to the brain. Considering
the blood-brain barrier, drug delivery approaches for AD is limited. To overcome this
problem, delivering the drug via the nasal route seems to be an appropriate approach as an
alternative way to the systemic administration due to direct targeting of the brain. In this
study, in order to optimize the drug delivery of AD, a new drug delivery system as a
mucoadhesive in-situ forming hydrogel for Galantamine was prepared To this end,
Mucoadhesive nanoparticles (NPs) were prepared by thiolation of chitosan (TCS) with
mercaptopropionic acid. The number of thiol groups was measured using Ellmans reagent
(DTNB dye). The Galantamine-loaded TCS NPs were synthesized by the two ionic gelation
methods (via sodium tripolyphosphate) and desolvation technique (via Glutaraldehyde).
After ultracentrifugation, the entrapment efficiency of Galantamine was estimated by a UV
spectrophotometer at λmax of 289 nm. Three different concentrations of Poloxamer solution
were prepared by the cold method. The concentration with the suitable gelation time and
gelation temperature was then attained. The amount of the Galantamine-loaded NPs required
as the therapeutic dose was calculated based on the entrapment efficiency. Two different
amounts of NPs containing the drug were dispersed in 4 mL of poloxamer 18% gel and the
achieved hydrogel at 37 ℃ was then sonicated. In-vitro release studies were carried out in
pH 6.4 phosphate-buffered saline media using the dialysis bag. Fourier transform infrared
(FT-IR) spectroscopy was used to analyze the structure of prepared formulations. In-vitro
cell cytotoxicity of prepared hydrogel on CaCO2 cells (nasal mucosal cell model) was
evaluated using the MTT method. The cell viability of hydrogels was determined by DAPIstaining and live/dead kit, too. The obtained results demonstrated that the thiolation value of
CS was 198.6 ± 18.7 µmol S. g-1 CS, which is a convenient result based on reported works.
In the preparation of TCS NPs via the ionic gelation method, by increasing the amount of
TPP, the particle size increased and the zeta potential decreased. The mean size and zeta
potential of NPs prepared by the desolvation method were 238.7 nm and 22.9 mV,
respectively. The drug entrapment efficiency of Galantamine in the prepared NPs by ionic
gelation method was zero, while the prepared NPs by desolvation method indicated
encapsulation efficiency equal to 30%. As the concentration of Poloxamer 407 solution
increased, gelling temperature and the time required for gelling decreased. Thus, according
to the temperature of the intranasal environment (32-35 °C), Poloxamer 18% has the best
concentration to prepare in-situ forming hydrogel for drug delivery via the intranasal route.
Drug release from the hydrogel containing drug loaded-TCS NPs was slower and more
controlled compared to the hydrogel containing the drug without NPs, which will lead to
more effective drug delivery. Our results confirmed that Poloxamer hydrogels containing
drug-loaded-TCS NPs are non-toxic for encapsulation of Galantamine and indicated high
cell viability. |