Effects of medicinal plants on radiolabeling and biodistribution of diagnostic radiopharmaceuticals: A systematic review

Radiopharmaceuticals are drugs that contain radioisotopes used for diagnostic and therapeutic purposes. There are evidences that medicinal herbs and their constituents can modify the radiolabeling, biodistribution, and pharmacokinetics of radiopharmaceuticals through drug interaction. To have an overview of the effects and the underlying mechanisms of medicinal plants on the radiolabeling and bioavailability of radiopharmaceuticals, we conducted this study to summarize the current findings in this field. The scientific literature was systematically collected from databases and analyzed. Studies showed that medicinal plants and their constituents can alter radiolabeling and biodistribution via several mechanisms. Interactions with proteins in red blood cells at the same sites, chelating action of stannous and pertechnetate ions, antioxidant action impeding or decreasing stannous ion oxidation, direct oxidation of stannous ions, generation of reactive oxygen species (ROS) which oxidize stannous ions and damage induced in the cell membrane. Most the medicinal plants can decrease the radioactivity of radiopharmaceuticals, but some of them like Peumus boldus, Punica granatum, Nectandra membranacea, Mentha crispa, Rosmarinus officinalis and derivatives such as eugenol and epigallocatechin gallate have increasing effects. In addition, altering feature in some of them is tissue dependent

Selegiline induced differentiation of rat bone marrow mesenchymal stem cells to dopaminergic neurons in vitro

Today, the use of mesenchymal stem cells (MSCs) for treating human diseases has attracted wide attention. The aim of this study is the expression of dopaminergic genes such as Nestin, patched Tumor Suppressor (PTCH), Sonic Hedgehog (SHH), Tyrosine Hydroxylase (TH) and Nuclear receptor-related factor 1 (NURR1) in MSCs after induction with selegiline. Rat bone marrow mesenchymal stem cells (rBMSCs) were extracted from femur and tibia bones and incubated with alpha Minimum Essential Medium (α-MEM) and 10% Fetal bovine serum (FBS). The stemness of cells at passage 4 was determined by the positive response to CD71 and CD90 markers and their differentiation into adipocytes and osteoblasts. The expression of SHH, PTCH, TH, NURR1 and Nestin genes in the cells after induction by 10-8 M selegiline for 48 hours was investigated by Reverse transcription polymerase chain reaction (RT-PCR) and Real Time-PCR methods. Isolated rBMSCs expressed CD71 and CD90 markers in culture conditions and could differentiate into adipocytes and osteoblasts. Induced cells showed neuronal morphology, positive response to Nestin and TH immunostaining. There was a significant increase of dopaminergic genes TH and NURR1 compared to the untreated cells. The results showed that selegiline with a dose of 10-8 M for 48 hours can lead to dopaminergic differentiation in rBMSCs

siRNA delivery using intelligent chitosan-capped mesoporous silica nanoparticles for overcoming multidrug resistance in malignant carcinoma cells

Although siRNA is a promising technology for cancer gene therapy, effective cytoplasmic delivery has remained a significant challenge. In this paper, a potent siRNA transfer system with active targeting moieties toward cancer cells and a high loading capacity is introduced to inhibit drug resistance. Mesoporous silica nanoparticles are of great potential for developing targeted gene delivery. Amino-modified MSNs (NH2-MSNs) were synthesized using a modified sol-gel method and characterized by FTIR, BET, TEM, SEM, X-ray diffraction, DLS, and H-1-NMR. MDR1-siRNA was loaded within NH2-MSNs, and the resulting negative surface was capped by functionalized chitosan as a protective layer. Targeting moieties such as TAT and folate were anchored to chitosan via PEG-spacers. The loading capacity of siRNA and the protective effect of chitosan for siRNA were determined by gel retardation assay. MTT assay, flow cytometry, real-time PCR, and western blot were performed to study the cytotoxicity, cellular uptake assay, targeting evaluation, and MDR1 knockdown efficiency. The synthesized NH2-MSNs had a particle size of approximate to 100 nm and pore size of approximate to 5 nm. siRNA was loaded into NH2-MSNs with a high loading capacity of 20% w/w. Chitosan coating on the surface of siRNA-NH2-MSNs significantly improved the siRNA protection against enzyme activity compared to naked siRNA-NH2-MSNs. MSNs and modified MSNs did not exhibit significant cytotoxicity at therapeutic concentrations in the EPG85.257-RDB and HeLa-RDB lines. The folate-conjugated nanoparticles showed a cellular uptake of around two times higher in folate receptor-rich HeLa-RDB than EPG85.257-RDB cells. The chitosan-coated siRNA-NH2-MSNs produced decreased MDR1 transcript and protein levels in HeLa-RDB by 0.20 and 0.48-fold, respectively. The results demonstrated that functionalized chitosan-coated siRNA-MSNs could be a promising carrier for targeted cancer therapy. Folate-targeted nanoparticles were specifically harvested by folate receptor-rich HeLa-RDB and produced a chemosensitized phenotype of the multidrug-resistant cancer cells

Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation

Resistance to temozolomide (TMZ) is the main cause of death in glioblastoma multiforme (GBM). The use of nanocarriers for drug delivery applications is one of the known approaches to overcome drug resistance. This study aimed to investigate the possible effect of selenium-chitosan nanoparticles loaded with TMZ on the efficacy of TMZ on the expression of MGMT, E2F6, and RELA genes and the rate of apoptosis in the C6 cell line. Selenium nanoparticles (SNPs) were loaded with TMZ and then they were coated by Eudragit(R) RS100 (Eud) and chitosan (C-S) to prepare Se@TMZ/Eud-Cs. Physicochemical properties were determined by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDAX), thermal gravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) methods. Se@TMZ/Eud-Cs was evaluated for loading and release of TMZ by spectrophotometric method. Subsequently, SNPs loaded with curcumin (as a fluorophore) were analyzed for in vitro uptake by C6 cells. Cytotoxicity and apoptosis assay were measured by MTT assay and Annexin-PI methods. Finally, real-time PCR was utilized to determine the expression of MGMT, E2F6, and RELA genes. Se@TMZ/Eud-Cs was prepared with an average size of 200 nm as confirmed by the DLS and microscopical methods. Se@TMZ/Eud-Cs presented 82.77 +/- 5.30 loading efficiency with slow and pH-sensitive release kinetics. SNPs loaded with curcumin showed a better uptake performance by C6 cells compared with free curcumin (p-value < 0.01). Coated nanoparticles loaded with TMZ showed higher cytotoxicity, apoptosis (p-value < 0.0001), and down-regulation of MGMT, E2F6, and RELA and lower IC50 value (p-value < 0.0001) than free TMZ and control (p-value < 0.0001) groups. Using Cs as a targeting agent in Se@TMZ/Eud-Cs system improved the possibility for targeted drug delivery to C6 cells. This drug delivery system enhanced the apoptosis rate and decreased the expression of genes related to TMZ resistance. In conclusion, Se@TMZ/Eud-Cs may be an option for the enhancement of TMZ efficiency in GBM treatment

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Abstract: Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer

Preparation and Administration of a Controlled-Release Delivery System of Chitosan Hydrogel loaded with Methadone and Piroxicam in Experimental Defect of Tibial in Rats; Histopathological Evaluation

Purpose: In this study, a controlled release drug delivery system loaded with piroxicam and methadone was synthesized and used subcutaneously in rat with experimental tibial defect and healing were assessed histopathologically. Materials and Methods: For this purpose 100 adult female rats were were randomly divided into five equal groups; group control, chitosan group, piroxicam group, methadone group, and piroxicam-methadone group. The morphological structure of the synthesized drug systems was studied by scanning electron microscope. In addition, the structure of the hydrogels was investigated by fourier transform infrared spectroscopy and while releasing the hydrogels gelation time, the release of piroxicam and methadone from the hydrogels were evaluated in vitro.   Results: Histological results of the 3rd day of the study showed the lowest extent and severity of inflammation in the chitosan, piroxicam, and piroxicam-methadone groups, while on the 7th day, tissue inflammation and the extent of bleeding was lower in the piroxicam, methadone, and piroxicam-methadone groups than in the other groups. Evaluation of new bone formation on day 21 showed that the chitosan, piroxicam, and methadone groups had better repair than the other groups. Conclusion: It seems that in the control group that did not receive any treatment intervention, following the experimental bone defect, the highest inflammatory response was observed in histological examination and finally the weakest bone repair. On the other hand, the presence of piroxicam, methadone and chitosan in the piroxicam-methadone group (all of which have anti-inflammatory effects) also seems to have a negative effect on repair

Preparation and evaluation of a thermosensitive liposomal hydrogel for sustained delivery of danofloxacin using mesoporous silica nanoparticles

BACKGROUND: Sustained release delivery system can reduce the dosage frequency and maintain the therapeutic level of drugs for a longer time. Biodegradable, biocompatible and thermosensitive chitosan-beta-glycerophosphate (C-GP) solutions can solidify at body temperature and maintain their physical integrity for a longer duration. OBJECTIVES: To develop a novel delivery system based on the integration of liposomes in hydrogel using mesoporous silica nanoparticles (MSNs) for sustained release of danofloxacin in farm animals. METHODS: The MSNs were prepared using N-cetyltrimethylammonium bromide and tetraethylortho silica. The liposomes were prepared by thin film hydration method. C-GP solution containing danofloxacin-loaded MSN liposomes underwent different in-vitro tests, including evaluation of the entrapment efficiency, gelation time, morphology, drug release pattern as well as antimicrobial activities against S. aureus and E. coli. RESULTS: The mean pore size of MSNs was 2.8 nm and the mean MSN entrapment efficiency was 45%. Kinetics of danofloxacin release from liposomal hydrogel followed the Higuchi’s model. This formulation was capable of sustaining the danofloxacin release for more than 96 h. The FTIR studies showed that there were no interactions between danofloxacin and hydrogel excipients. Scanning electron microscopy (SEM) showed that the formed gel had a continuous texture, while the swelled gel in the phosphate buffer had a porous structure. Microbiological tests revealed a high antibacterial activity for lipomosal hydrogel of danofloxacin-loaded MSN comparable with danofloxacin solution. CONCLUSIONS: The liposomal hydrogel solidified at body temperature, effectively sustained the release of danofloxacin and showed in vitro antibacterial effects

Association of body mass index and physical activity with fatigue, depression, and anxiety among Iranian patients with multiple sclerosis

IntroductionDepression, fatigue, and anxiety are three common clinical comorbidities of multiple sclerosis (MS). We investigated the role of physical activity (PA) level and body mass index (BMI) as modifiable lifestyle factors in these three comorbidities.MethodsA cross-sectional study was conducted in the MS specialist clinic of Sina Hospital, Tehran, Iran. Demographic and clinical data were collected. BMI was categorized in accordance with the WHO’s standard classification. Physical activity (PA) level and sitting time per day were obtained using the short form of the International Physical Activity Questionnaire (IPAQ-SF). Fatigue, anxiety, and depression scores were measured using the Persian version of the Fatigue Severity Scale (FSS), Beck Anxiety Inventory (BAI), and Beck’s Depression Inventory II (BDI-II) questionnaires, respectively. The correlation between the metabolic equivalent of tasks (MET), BMI, and daily sitting hours with depression, anxiety, and fatigue were checked using the linear regression test. The normal BMI group was considered a reference, and the difference in quantitative variables between the reference and the other groups was assessed using an independent sample t-test. Physical activity was classified with tertiles, and the difference in depression, anxiety, and fatigue between the PA groups was evaluated by a one-way ANOVA test.ResultsIn total, 85 MS patients were recruited for the study. The mean ± SD age of the participants was 39.07 ± 8.84 years, and 72.9% (n: 62) of them were female. The fatigue score was directly correlated with BMI (P: 0.03; r: 0.23) and sitting hours per day (P: 0.01; r: 0.26) and indirectly correlated with PA level (P &lt; 0.01; r: −0.33). Higher depression scores were significantly correlated with elevated daily sitting hours (P: 0.01; r: 0.27). However, the correlation between depression with PA and BMI was not meaningful (p &gt; 0.05). Higher anxiety scores were correlated with BMI (P: 0.01; r: 0.27) and lower PA (P: 0.01; r: −0.26). The correlation between anxiety and sitting hours per day was not significant (p &gt; 0.05). Patients in the type I obesity group had significantly higher depression scores than the normal weight group (23.67 ± 2.30 vs. 14.05 ± 9.12; P: 0.001). Fatigue (32.61 ± 14.18 vs. 52.40 ± 12.42; P: &lt;0.01) and anxiety (14.66 ± 9.68 vs. 27.80 ± 15.48; P: 0.01) scores were significantly greater among participants in the type II obesity group in comparison with the normal weight group. Fatigue (P: 0.01) and anxiety (P: 0.03) scores were significantly different in the three levels of PA, but no significant difference was found in the depression score (P: 0.17).ConclusionOur data suggest that a physically active lifestyle and being in the normal weight category are possible factors that lead to lower depression, fatigue, and anxiety in patients with MS

In vitro antiviral activity of curcumin-loaded selenium nanoparticles against human herpes virus type 1

Background and aims: Herpes simplex type 1 (HSV-1) is one of the most common and contagious viruses in humans. Curcumin is a natural polyphenol that produces antiviral effects against various viruses, such as HSVs. Despite curcumin’s numerous effects and benefits, its insolubility has reduced its clinical effectiveness. During recent decades, significant progress has been made in nanodrugs, which has helped expand new delivery systems. This study investigated the in vitro antiviral activity of curcumin-loaded, folic acid-chitosan-coated selenium nanoparticles (SeNP) against HSV-1. Methods: Synthesized SeNPs loaded with curcumin and coated with folic acid-chitosan molecules were used in this experimental study. The studied groups comprised cells and the virus-containing curcumin, acyclovir, and NPs with or without curcumin. The cytotoxicity of the compounds was evaluated on Vero cells using the MTT assay. Antiviral activity was investigated using the MTT colorimetric assay, and the inhibitory effect on HSV-1 was studied using a 50% tissue culture infectious dose assay. Results: The results of this research demonstrated that curcumin (50% inhibitory concentration [IC50]=5.64 µg/mL) and curcumin-loaded SeNPs (IC50=1.15 µg/mL) exhibited satisfactory antiviral potential against HSV-1 in vitro, while curcumin-loaded, folic acid-chitosan-coated SeNPs produced no antiviral effect against HSV-1 due to increased cytotoxicity. Conclusion: Based on the findings, the curcumin and curcumin-loaded SeNPs had acceptable antiviral potential against HSV-1. Loading curcumin with SeNPs makes the compound more active at a lower concentration, and therefore, lower doses can be administered to treat HSV-1 infection

Poly-l-lactic acid scaffold incorporated chitosan-coated mesoporous silica nanoparticles as pH-sensitive composite for enhanced osteogenic differentiation of human adipose tissue stem cells by dexamethasone delivery

Nowadays, the development of drug-loaded electrospun organic-inorganic composite scaffolds for tissue engineering application is an attractive approach. In this study, a composite scaffold of Poly-l-lactic acid (PLLA) incorporated dexamethasone (Dexa) loaded Mesoporous Silica Nanoparticles (MSN) coated with Chitosan (CS) were fabricated by electrospinning for bone tissue engineering application. The MSN was prepared by precipitation method. After that, Dexamethasone (Dexa) was loaded into MSNs (MSN-Dexa). In the following, CS was coated over the prepared nanoparticles to form MSN-Dexa@CS and then, were mixed to PLLA solution to form MSN-Dexa@CS/PLLA composite for electrospinning. The surface morphology, hydrophilicity, tensile strength and the bioactivity of the scaffolds were characterized. The osteogenic proliferation and differentiation potential were evaluated by MTT assay and by measuring the basic osteogenic markers: the activity of the enzyme alkaline phosphatase and the level of calcium deposition. The composite scaffolds prepared here have conductive surface property and have a better osteogenic potential than pure PLLA scaffolds. Hence, the controlled release of nanoparticle containing Dexa from composite scaffold supported the osteogenesis and made the composite scaffolds ideal candidates for bone tissue engineering application and pH-sensitive delivery of drugs at the site of implantation in tissue regeneration. Keywords Author Keywords:Mesoporous silica nanoparticles; electrospinning; Poly-l-lactic acid; chitosan; dexamethasone; composite scaffold; bone tissue engineering KeyWords Plus:DRUG-DELIVERY; BONE; SYSTEM; NANOFIBERS; SURFACE; POLY(L-LACTIDE); PROLIFERATION; CARTILAGE; RELEASE; PEPTID