Parkinson’s disease (PD) is a chronic, progressive, and age-related neurodegenerative disorder characterized by the loss of midbrain dopaminergic neurons caused by the accumulation of free radicals and oxidative stress. Based on the neuroprotective properties of 2-pyrazoline derivatives, in the current work, 1-(phenyl/4-substituted phenyl)-3-(2-furanyl/thienyl)-5-aryl-2-pyrazolines (3a–i, 4a–i) were synthesized via the cyclization of the chalcones (1, 2) with suitable phenylhydrazine hydrochloride derivatives. All these compounds were investigated for their neuroprotective effects using an in vitro 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model of PD in the rat pheochromocytoma (PC-12) Adh cell line. In addition, some different pharmacokinetic parameters of all compounds were in silico predicted by the QikProp module of Schrödinger’s Maestro molecular modeling package. 4-Methylsulfonylphenyl substituted compounds 3h (20%) and 4h (23%) were determined as the most promising neuroprotective agents related to their inductive roles in cell viability when compared with the 6-OHDA-positive control group (43% and 42%, respectively). Moreover, in silico pharmacokinetic results indicated that all compounds were within the acceptable range intended for human use. According to both in vitro and in silico studies, compounds 3h and 4h draw attention as potential orally bioavailable therapeutic drug candidates against neurodegeneration in PD.
In this study, vitamin
A palmitate (VAP)-loaded poly(lactic-co-glycolic
acid) (PLGA)/chitosan-coated PLGA nanoparticle
(NP) systems were prepared by the nanoprecipitation technique. The
prepared systems were characterized by parameters such as particle
size, polydispersity index (PDI), ζ-potential, encapsulation
efficiency, in vitro dissolution, and release kinetic
study. Then, the cytotoxicity and wound healing profiles of the designed
NP formulations in HaCaT (human keratinocyte skin cell lines) were
determined. The particle size of VAP-loaded NPs was obtained between
196.33 ± 0.65 and 669.23 ± 5.49 nm. PDI data proved that
all NPs were prepared as high quality and monodisperse. While negative
ζ-potential values of Blank-NP-1 and NP-1 encoded PLGA NP formulations
were obtained, positive ζ-potential was obtained in chitosan-coated
NPs. In vitro release studies of NPs observed rapid
dissolution in the first 1–6 h, but prolonged dissolution of
VAP after rapid dissolution. As a result of cell culture studies and
wound healing activity studies, it was determined that NP-7 was the
most effective. It was thought that the reason for this was that the
NP-7 coded formulation was a chitosan-coated PLGA nanoparticle with
the smallest particle size, and it was concluded that the efficiency
of VAP was increased with its nanoparticle structure. This study demonstrated
the similar wound healing effects of VAP-loaded nanoparticle systems,
in particular NP-7, which increases keratinocyte cell proliferation
at lower concentrations (10 μg·mL–1)
than vitamin A alone (100 μg·mL–1). VAP-loaded
nanocarriers that can be used in the pharmaceutical industry have
been successfully produced and the results obtained have been evaluated
as promising for this industry.
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