Background: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD). Methods: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated. Results: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/beta-catenin pathway. The gene expression level of beta-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3 beta signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways. Conclusion: CNPSGS might be an effective therapeutic alternative for AD treatment.

Retinoic acid (RA) has been shown in earlier investigations to have anticancer properties in various cancer cells. RA’s effect on breast cancer treatment remains uncertain, though. This study investigated whether RA and chitosan nanoparticles (NPs) loaded with RA could be harmful to the MCF-7 cell line. In this study, NPs with RA were used in characterization tests. Using ELISA kits, the amounts of 8-okso-2′-deoksiguanozin (8-oxo-dG), BCL-2, Bcl-2-Associated X-protein (Bax), cleaved Poly (ADP-ribose) polymerases (PARP), total oxidant and antioxidant, and cleaved caspase-3 capacities were determined. The analysis of chitosan NPs showed that their drug-release profile, encapsulation efficiency (EE), and particle size were suitable for cell culture experiment. The EE value of NPs including RA was calculated as 83.32 ± 0.04

AbstractRecently developed nanoparticles and nanofibers present new brain‐specific treatment strategies, especially for Alzheimer's disease treatment. In this study, donepezil (DO)‐loaded PLGA nanoparticles (DNP) are embedded in PVA/PEG nanofibers (DNPF) produced by pressurized gyration for sublingual administration. SEM images showed produced drug‐loaded and pure nanofibers, which have sizes between 978 and 1123 nm, demonstrated beadless morphology and homogeneous distribution. FT‐IR, XRD, and DSC results proved the produced nanoparticles and fibers to consist of the DO and other polymers. The in vitro drug release test presented that the release profile of DO is completed at the end of the 18th day. It is released by the first order kinetic model. DNPF has an ultra‐fast release profile via its disintegration within 2 sec, which proved itself to be suitable for the administration sublingually. All samples presented above ≈90% cell viability via their non‐toxic natures on SH‐SY5Y human neuroblastoma cells by using Alamar blue assay. The anti‐Alzheimer effects of DO, DNP, and DNPF are evaluated on the Aβ1−42‐induced SH‐SY5Y cells at 1, 5, and 10 µM as treatment groups. The 1 µM dosage exhibited the most significant neuroprotective effects, which showed enhanced cellular uptake and superior modulation of Alzheimer's‐related proteins, including tau and Aβ.

The biological activities of different parts of the Rheum ribes plant were evaluated comparatively. Extracts showing strong biological activity were identified and it was determined which of the extract-loaded nanoparticles showed stronger activity. Cytotoxic activity of R. ribes extracts was calculated on glial (C6) and fibroblast (NIH 3T3) cells using XTT assay. Spectrophotometry was used to evaluate the impact of these compounds on the enzyme activities of human carbonic anhydrase I and II (hCA I and hCA II). The findings showed that chitosan NPs with extracts loaded on them have a lower IC50 value and more cytotoxic activity in C6 cells than chitosan NPs with only extracts. R. ribes young shoots ultrasonic methanol extract (RYU) was shown to have the strongest antiproliferative efficacy against C6 cells. Results showed that RYU and ultrasonic methanol extract of R. ribes radix (RRU) were determined as the best carbonic anhydrase inhibitors. According to results of particle size, encapsulation efficiency, and release studies of chitosan NPs, it has been observed that they are suitable for application. At a concentration of 10 µg/mL, it was found that none of the R. ribes extracts exhibited cytotoxic action toward the NIH 3T3 cell line. According to results of particle size, encapsulation efficiency, and release studies of chitosan NPs, it has been observed that they are suitable for application. It was observed that none of the extracts of R. ribes at a concentration of 10 µg/mL showed cytotoxic activity in the NIH 3T3 cell line.

Nutritional supplements available in various forms provide the consumer with essential molecules demanded for well-being retention. Despite the conveniences provided by oral administration, significant disadvantages such as hepatic first-pass effect, limited absorption, and age-related swallowing problems have been recognized which should be addressed appropriately. Nano-sized biomaterials, which have recently gained popularity in numerous medical fields, have the potential to resolve these problems. In this study, a drug delivery system was designed for sublingual administration and fabricated as (3-glucan/vitamin C-loaded chitosan/tripolyphosphate/polyvinylpyrrolidone (CS/TPP/PVP) nanoparticles (DNPs) embedded in polyethylene oxide (PEO) nanofibrous mats (DNFs). The optimum PNP size and DNP size for sublingual administration were obtained as 236 +/- 1 nm and 257 +/- 1 nm, respectively. The homogenous appearance of DNFs was demonstrated and measured as 783 +/- 290 nm using scanning electron microscopy. The synthesized biomaterials were analyzed chemically, 3D-wisely, and thermally. The in vitro drug release kinetics investigation concluded that the sustained drug release of DNP over 15 days proceeded based on the first-order model, and 99.30 % of vitamin C and 99.70 % of (3-glucan were released. Neither pure nor drug-loaded samples showed notable cytotoxicity in the 24-h 3-[4,5-dimethylthiazol2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the L929 cell line. Herein, it has been comprehended that DNF nutritional supplement can be a promising novel supplement dosage form with ease of use, high efficiency, and bioavailability than the conventional methods.

Alzheimer's disease (AD) is a neurodegeneration type that is biologically recognizable via β-amyloid plaques and tau neurofibril tangles. Global estimation for the total count of individuals enduring AD will rise up to 131 million by 2050. Investigations suggested the existence of a direct proportion between the likelihood of AD occurrence and vitamin B12 (VB12) hypovitaminosis. Approved VB12 administrations, intramuscular and oral, each has serious defects broaching the demand for alternative routes. This work developed VB12-loaded chitosan/tripolyphosphate/polyvinyl alcohol (CS/TPP/PVA) nanoparticles (NPs) embedded in polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone/polycaprolactone (PVP/PCL) nanofibrous (NFs) produced by pressurized gyration (PG) for sublingual and transdermal routes, respectively. Biomaterials were investigated morphologically, chemically, and thermally. Moreover, degradation, disintegration, release behavior, and release kinetics were analyzed. The effectiveness and safety of nanomaterials were assessed and proven with the alamarBlue test on the Aβ1–42-induced SH-SY5Y model. The final evaluation suggested the feasibility, safety, and effectiveness of produced systems. Consequently, two alternative VB12 application routes were developed with high effectivity and low toxicity with the power of nanotechnology.

In the present work, a series of compounds containing imidazole and hydrazone structural frameworks were synthesized and characterized using various spectral techniques, including 1H NMR, 13C NMR, FTIR, and HRMS. Synthesized compounds were subjected to screening as antiproliferative agents as well as against two physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I and hCA II. Among them, some compounds exhibited remarkable antiproliferative activity with less cytotoxicity activity to healthy cells and significant CA inhibitory activities in contrast to a standard inhibitor with Ki values in the range of 0.49 +/- 1.010-739.12 +/- 111.35 nM for hCA I (Ki value for standard inhibitor = 271.15 +/- 74.620 nM), 64.53 +/- 19.44-314.37 +/- 54.78 nM for hCA II (Ki value for standard inhibitor = 113.07 +/- 20.980 nM). In addition, DFT calculations were performed to get insight into the distinctive reactive sites of all compounds, and subsequently, the reactive centers of the compounds were determined. Moreover, molecular docking studies of the most potent compounds were conducted, and results showed reasonable binding modes in the active sites of hCA I protein (PDB ID: 2CAB), hCA II protein (PDB ID: 3DC3), as well as colon cancer protein (PDB ID: 4UYA and 3DTC). Finally, in silico predictions of ADME and pharmacokinetic parameters indicated that these compounds should have good oral bioavailability.

Antiproliferative activity of Achillea vermicularis extracts was calculated on glial (C6) and keratinocyte (HaCaT) cell lines using XTT assay. It was observed that all extracts of A. vermicularis at the determined concentration were not cytotoxic in HaCaT cell lines. The nanoparticles (NPs) of the extract with the best cytotoxic activity was prepared, and necessary characterization studies were performed. Results showed that NP containing the extract has a lower IC50 value and more cytotoxic activity in C6 cells compared to the only extract. Furthermore, the antiepileptic potentials of these substances were explored in this study. The effect of A. vermicularis extracts on the enzyme activities of carbonic anhydrase I and II isoenzymes (hCA I and hCA II) was measured using spectrophotometry to achieve this goal. A. vermicularis extracts demonstrated high inhibitory activities compared to standard inhibitor (acetazolamide, AAZ), with IC50 values in the range of 5.04-10.8 μg/ml for hCA I, and 5.40-9.22 μg/ml for hCA II. High-performance liquid chromatography diode array detector (HPLC-DAD) was used in this investigation to assess the main chemicals found in the extract and NPs. The results showed that the ethanol extract (157.636 μg/mg extract) and NPs (4.631 μg/mg extract) had a significant amount of the 8-hydroxy salvigenin component.

In this study, antioxidant and antiproliferative properties of ‘‘ Achillea phrygia’’ were investigated. Since the antioxidant and antiproliferative activity of B sub-extract from plant’s chloroform extract is higher than other extracts, B sub-extract of Achillea phrygia was used in the preparation of nanoparticles. Characterization of nanoparticles was made, antiproliferative activities and IC 50 values of nanoparticles and only chloroform extract was calculated by cell culture studies and XTT cell viability test. According to the results, it was observed that the extract-loaded chitosan nanoparticles had a strong antiproliferative activity in both MCF 7 and HT29 cells. The results of this study support that bioactive extract of the Achillea phrygia plant can be prepared as an herbal medicine candidate by preparing formulations with biopolymers and being investigated in cancer studies.

Objective: In this study, it was aimed to prepare nanoparticle formulations using chitosan, a cationic natural polymer, and tripoly phosphate, and to perform mechanical characterization and in vitro cell culture studies. In addition, the cytotoxic effects of nanoparticles containing indenopyrazol derivatives against human glioma cells (C6) and human cervical cancer cells (HeLa) were investigated. Methods: Within the scope of the study, nanoparticles containing indenopyrazole derivative were prepared and characterization of particle size, zeta potential and morphological properties were performed. XTT cytotoxicity test was applied to evaluate the antiproliferative activities of nanoparticles containing these components. Results: Particle size, zeta potential and morphological properties of nanoparticles were observed to be suitable for application. In vitro cell culture studies showed that nanoparticles containing indenopyrazol derivatives showed better cytotoxic effects in both cell lines. Conclusion: The results showed that the mechanical properties of nanoparticles containing indenopyrazol derivatives are suitable and can be applied in anticancer activity studies.

Purpose: In this study, it is aimed to prepare chitosan nanoparticles containing shRNA-VEGF and evaluate their bioactivity by in vitro cell culture studies and to perform mechanical characterization of nanoparticles. Material and Methods: Ionic chelation method was used to prepare nanoparticles. The XTT assay was used to assess the cytotoxic activity of shRNA-VEGF and shRNA-VEGF loaded NP on the HeLa and NIH 3T3 cells. Results: According to the results IC50 values of shRNA-VEGF and NP including shRNA-VEGF were calculated. IC50 values of shRNA-VEGF and NP including shRNA-VEGF were 0.89±0.010 µg/mL and 0.52±0.004 µg/mL on HeLa cell line. Bax quantities of control, shRNA-VEGF, and shRNA-VEGF loaded NP was measured as 23.70±0.27 ng/mg protein, 34.64±0.36 ng/mg protein, and 39.46±0.54 ng/mg protein, respectively. According to the results, cleaved caspase 3 quantities of control, shRNA-VEGF, and shRNA-VEGF loaded NP was measured as 711.70±4.40 pg/mg protein, 767.23±3.82 pg/mg protein, and 825.32±5.06 pg/mg protein, respectively. Conclusion: shRNA-VEGF and shRNA-VEGF loaded NP significantly reduced HeLa cell reproduction in a concentration-dependent manner while generating no cytotoxicity in NIH 3T3 cells. The expression of pro-apoptotic Bax and cleaved caspase 3 proteins was significantly increased by shRNA-VEGF and shRNA-VEGF loaded NP.

In this study, firstly, 22 thiosemicarbazone derivatives (3a-y) were synthesized. Then, ADME parameters, pharmacokinetic properties, drug-like structures, and suitability for medicinal chemistry of these molecules were studied theoretically by using SwissADME and admetSAR programs. According to the results of these theoretical studies, it can be said that the bioavailability and bioactivity of these compounds may be high. In silico molecular docking between ligands (thiosemicarbazone derivatives) and targeted proteins (protein-78 (GRP78) for C6 and quinone reductase-2 (4ZVM for MCF 7) was analyzed using Hex 8.0.0 docking software. According to the docking data, almost all molecules had higher negative E values than Imatinib (already used as a drug). For this, in vitro anticancer studies of these molecules were done. The cytotoxic activities of thiosemicarbazone derivatives (3a-y) were evaluated on C6 glioma and MCF7 breast cancer cell lines at 24 h, and Imatinib was used as the positive control. According to the results of the cytotoxicity assay, it can be said that the five compounds (3b, c, f, g, and m with IC50 = 10.59–9.08 μg/mL; Imatinib IC50 = 11.68 μg/mL) showed more potent cytotoxic activity than Imatinib on C6 cell line. Together with to these results ten compounds (3b, d, f, g, I, k, l, m, n, and r with IC50 = 7.02–9.08 μg/mL; Imatinib IC50 = 9.24 μg/mL) had a more effective cytotoxic activity against MCF7 cell line than Imatinib. Compound 3 m showed the highest antiproliferative effect against C6 and MCF7 cell lines.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Design, synthesis, structural elucidation, and investigation of cytotoxic and antimicrobial activity, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) enzyme inhibition effects of isatinthiosemicarbazone hybrid compounds ( 1 -15 ) are reported in this study. Hybrid compounds ( 14 and 15 ) were synthesized, isolated, and characterized for the first time. FT-IR, 1 H NMR, and 13 C NMR spectroscopic methods and elemental analysis were used to characterize the structures of the compounds. In the enzymatic evaluation, hybrid compound 13 was observed as the most potent inhibitor of AChE with a K I value of 0.94 +/- 0.13 mu M (all compound K I values between 0.94 +/- 0.13 and 4.47 +/- 0.92), also this compound was observed as the most potent inhibitor of BChE with a K I value of 0.82 +/- 0.11 mu M (all compounds had K I values between of 0.82 +/- 0.11 and 3.48 +/- 0.92). Almost all compounds were shown better inhibition profile than standard compound. In the theoretical calculations, the comparison of the biological activities of isatin-thiosemicarbazone hybrid derivatives against enzymes was studied. The enzymes studied in docking calculations are AChE and BChE. Then, ADME/T analysis was conducted to examine the drug properties of these derivatives. Besides, the antimicrobial activity of these molecules was investigated by the microdilution method according to Clinical Laboratory Standards Institute (CLSI) criteria in the study. Cytotoxic activity of isatin-thiosemicarbazone hybrids was determined by the XTT cell viability assay on human breast cancer cell lines MCF-7 and MDA-MB-231. Among the hybrid compounds, compound 8 exhibited the most potent cytotoxic activity with IC 50 values of 23.42 +/- 0.21 mu g/mL and 19.68 +/- 0.23 mu g/mL on MCF-7 and MDA-MB-231 cell lines, respectively. Overall, the hybridization of isatin and thiosemicarbazone skeleton has played an essential role in the inhibition of enzymes and cytotoxic activity.

Objective: In this study, it was aimed to make in vitro characterization of the formulations by preparing hydrogel formulations using chitosan, a biocompatible and natural polymer, and PVP, a synthetic polymer. In addition, the effects of hydrogels containing FGF on the proliferation of keratinocyte cells were investigated. Methods: Within the scope of the study, hydrogels with different properties were prepared and their water absorption capacity, and viscosities were examined. In addition, the hardness, adhesiveness, cohesiveness, and elasticity properties of hydrogels were investigated. The 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyl tetrazolium bromide (MTT) test was applied to evaluate the toxicity of hydrogels on keratinocyte cell lines. Results: It was observed that hydrogel formulations have high water absorption capacity and suitable viscosity values. In addition, the mechanical characterization results showed that the hydrogels have suitable mechanical properties. According to the results of in vitro cell culture studies, it has been observed that hydrogels stimulate the proliferation of keratinocyte cells. Conclusion: Results showed that the mechanical properties of hydrogels containing FGF are suitable for application and according to the results of in vitro cell culture studies, hydrogels can be used in wound healing studies because they increase keratinocyte cell proliferation.

Cancer is a complex disease involving several important changes in cell morphology that ultimately lead to tumor formulation. The biological endpoint of cancer is the uncontrolled growth and proliferation of cells. Resveratrol (RES) is a polyphenolic compound from the stilbene family, which has an important place in the treatment of cancer, which is used as a pharmaceutical and nutraceutical. Studies have shown that RES has anti-tumor effects in addition to its antioxidant, antimicrobial and anti-inflammatory effects. RES protects the body against free radicals and inhibits metabolic events that induce the proliferation of cancer cells. RES is a chemically unstable compound that has problems crossing the blood-brain barrier. Therefore, it is concluded that carrier systems containing RES should be developed in order to increase the water dispersibility of resveratrol and to increase its bioavailability when taken orally. In this way, the RES will be successfully targeted to the tumor site and the undesirable properties of the unstable, heat-sensitive RES will be improved. For this purpose, drug delivery systems prepared using synthetic polymers such as Polylactic-co-glycolic acid (PLGA) have been developed. PLGA is a biodegradable and biocompatible polymer used in areas related to human health. In this study, cell culture study of C6 glioma cells obtained from ATCC was performed and for this purpose, biocompatible nanoparticles of RES with PLGA were prepared. With the preparation of these nanoparticles, the effects of RES on cell viability and the differences in the anticancer effect on cells were evaluated with the XTT cytotoxicity study.

The aim of the current study was to assess the physicochemical characteristics and wound healing activity of chitosan-polyvinyl alcohol (PVA) crosslinked hydrogel containing recombinant human epidermal growth factor (rh-EGF) or recombinant mouse epidermal growth factor (rm-EGF).The hydrogels were prepared and analyses were made of the morphological properties, viscosity, water absorption capacity, mechanical and bio-adhesive properties.The viscosity of the formulations varied between 14.400 -48.500 cPs, with the greatest viscosity values determined in K2 formulation.F2 formulation showed the highest water absorption capacity.According to the studies of the mechanical properties, H2 formulation (0.153±0.018N.mm) showed the greatest adhesiveness and E2 (0.245±0.001 mj/cm 2 ) formulation, the highest bio-adhesion values.Hydrogels were cytocompatible considering in vitro cell viability values of over 76% on human keratinocyte cells (HaCaT, CVCL-0038) and of over 84% on human fibroblast cells (NIH 3T3, CRL-1658) used as a model cell line.According to the BrdU cell proliferation results, B1 (197.82±2.48%)formulation showed the greatest NIH 3T3 and C1 (167.43±5.89%)formulation exhibited the highest HaCaT cell proliferation ability.In addition, the scratch closure assay was performed to assess the wound healing efficiency of formulation and the results obtained in the study showed that F2 formulation including PEGylated rh-EGF had a highly effective role.

A new series of imidazolyl hydrazone derivatives IA ( 1-12 ) were prepared from a condensation reaction between indoline-2,3-dione (isatin) and 2-benzylidenehydrazinecarboximidamide derivatives. The struc-ture of compounds was elucidated using various spectral techniques including FTIR, 1 H NMR, 13 C NMR, and HRMS. The proposed structure of IA-2 was determined by single-crystal X-ray analysis. Synthesized compounds were evaluated for their inhibitory action against carbonic anhydrase I and II isoenzymes (hCA I and hCA II), as well as cytotoxicity activity in a cancer cell line (HT-29) and a healthy cell line (NIH 3T3). Among them, some compounds exhibited remarkable CA inhibitory activities compared to a standard inhibitor with Ki values in the range of 13.434 +/- 3.278-522.549 +/- 360.720 nM for hCA I (Ki value for standard inhibitor = 271.15 +/- 74.620 nM) and 41.108 +/- 10.180-271.171 +/- 65.293 nM for hCA II (Ki value for standard inhibitor = 113.07 +/- 20.980 nM) and significant antiproliferative activity with less toxicity to a health cell line. In addition, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities and ADME/T analysis was carried out to examine the drug properties of the synthesized compounds.(c) 2022 Elsevier B.V. All rights reserved.

In prior studies, Quercetin was revealed to exhibit anti-cancer features in a variety of cancer cell lines. However, the impact of Quercetin on neuroblastoma is unknown. This study looked into the potential cytotoxic effects of Quercetin and Quercetin-loaded chitosan nanoparticles (NPs) on the SH-SY5Y cell line. In this study, NPs containing Quercetin was prepared and characterization studies were performed. The vitality of the cells was measured using the XTT test after 24 h of treatment with various concentrations of Quercetin (0.5, 1, 2, 4, and 8 µg/mL). ELISA kits were used to detect the amounts of cleaved PARP, BCL-2, 8-Hydroxy-deoxyguanosine (8-oxo-dG), cleaved caspase 3, Bax, total oxidant status, and total antioxidant status in the cells. The results of the chitosan NPs characterization investigation revealed that the particle size, encapsulation effectiveness, and drug release profile of NPs were all appropriate for cell culture studies. Quercetin and Quercetin-loaded chitosan NPs significantly reduced cell viability in SH-SY5Y cells at different concentrations (**p < 0.05). 2 µg/mL Quercetin and Quercetin-loaded chitosan NPs significantly enhanced the levels of 8-oxo-dG, cleaved caspase 3, Bax, cleaved PARP, and total oxidant in ELISA testing. However, treatment with 2 µg/mL of Quercetin and Quercetin-loaded chitosan NPs did not affect the amount of BCL-2 protein. Overall, Quercetin and Quercetin-loaded chitosan NPs caused significant cytotoxicity in SH-SY5Y cells via producing oxidative stress, DNA damage, and eventually apoptosis.

The present study aimed to prepare A. goniocephala chloroform extract and evaluate antioxidant and cytotoxic effects. Then, the nanoparticles (NPs) were synthesized on the most efficient extracts and the biological activities of the free forms of the extracts were compared with the NPs forms. Antioxidant capacities of 14 extracts by column chromatography were found by FRAP, DPPH and CUPRAC methods. Again, the cytotoxic activities of all fractions were evaluated on MCF-7 and HT-29 cell lines using the XTT cell viability assay. Chitosan-tripolyphosphate (TPP) NPs were formed using the ionic gelation method of H and F extracts, which show the most active properties because of biological activities. The biological activities of the characterized NPs were also evaluated. The synthesized particle size of the NPs from two extracts obtained between 274.12 and 296.25 nm. The extract-encapsulation and loading-efficiency of the most active NPs were 77.6± 0.04% and 7.76± 0.01% for F extract and 10.2± 0.02% and 1.39± 0.07% for H extract, respectively. Anticancer activity of chitosan NPs gave better results compared to unencapsulated extracts. As a result, it was found that the A. goniocephala extract can be encapsulated in chitosan NPs and has an antioxidant and more anticancer effect than the free forms.