Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study.

Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196 nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.

Quercetin-loaded solid lipid nanoparticles exhibit antitumor activity and suppress the proliferation of triple-negative MDA-MB 231 breast cancer cells: implications for invasive breast cancer treatment.

BACKGROUND: Quercetin (QC) is a naturally occurring flavonoid found in abundance in fruits and vegetables. Its anti-cancer and anti-inflammatory properties have been previously demonstrated, but its low bioavailability hampers its clinical use. Triple-negative breast cancer is a subtype of breast cancer with a poor response to chemotherapy. This study investigates the anti-cancer effects of quercetin-solid lipid nanoparticles (QC-SLN) on the triple-negative breast cancer cell line MDA-MB231. MATERIALS AND METHODS: MCF-7 and MDA-MB231 cells were treated with 18.9 µM of QC and QC-SLN for 48 h. Cell viability, apoptosis, colony formation assay, and the anti-angiogenic effects of the treatment were evaluated. RESULTS: QC-SLN displayed optimal properties (particle size of 154 nm, zeta potential of -27.7 mV, encapsulation efficiency of 99.6%, and drug loading of 1.81%) and exhibited sustained release of QC over 72 h. Compared to the QC group, the QC-SLN group showed a significant decrease in cell viability, colony formation, angiogenesis, and a substantial increase in apoptosis through the modulation of Bax and Bcl-2 at both gene and protein levels. The augmentation in the proportion of cleaved-to-pro caspases 3 and 9, as well as poly (ADP-ribose) polymerase (PARP), under the influence of QC-SLN, was conspicuously observed in both cancer cell lines. CONCLUSIONS: This study showcases quercetin-solid lipid nanoparticles (QC-SLN) as a promising therapy for triple-negative breast cancer. The optimized QC-SLN formulation improved physicochemical properties and sustained quercetin release, resulting in reduced cell viability, colony formation, angiogenesis, and increased apoptosis in the MDA-MB231 cell line. These effects were driven by modulating Bax and Bcl-2 expression, activating caspases 3 and 9, and poly (ADP-ribose) polymerase (PARP). Further in vivo studies are needed to confirm QC-SLN's efficacy and safety.

AS1411aptamer conjugated liposomes for targeted delivery of arsenic trioxide in mouse xenograft model of melanoma cancer.

Development of AS1411aptamer-conjugated liposomes for targeted delivery of arsenic trioxide is the primary goal of this study. AS1411aptamer was used as ligand to target nucleolin, which is highly expressed on the surface of melanoma cancer cells. The targeted liposomes were constructed by the thin film method, and arsenic trioxide was loaded as cobalt (II) hydrogen arsenite (CHA) to increase the loading efficiency and stability of the liposomes. The liposomal structure was characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and field emission scanning electron microscopy (FESEM). In addition, particle sizes and zeta potential of the CHA-loaded liposomes (CHAL) and aptamer-functionalized CHA-loaded liposomes (AP-CHAL) were determined. In vitro cytotoxicity of CHAL and AP-CHAL were evaluated using MTT assay in murine melanoma (B16) and mouse embryonic fibroblast (MEF) cell lines. The encapsulation efficiency of CHAL and AP-CHAL was reported as 60.2 ± 6.5% and 58.7 ± 4.2%, respectively. In vivo antitumor activity of CHAL and AP-CHAL in the B16 tumor-xenograft mouse model was dramatically observed. All mice of both groups survived until the end of treatment and showed body weight gain. The tumor protrusion completely disappeared in 50% of the mice in these groups. Furthermore, histopathology studies demonstrated that CHAL and AP-CHAL did not induce significant toxicity in healthy mice tissues. However, unlike the CHAL group, which showed an initial increase in tumor volume, a specific antitumor effect was observed in the AP-CHAL group from the beginning of treatment. The results showed that AP-CHAL can be used as an effective drug delivery system with high potential in the treatment of solid tumors.

Effective inhibition of breast cancer stem cell properties by quercetin-loaded solid lipid nanoparticles via reduction of Smad2/Smad3 phosphorylation and ß-catenin signaling pathway in triple-negative breast cancer.

BACKGROUND: The presence of cancer stem cells (CSCs) is a major cause of resistance to cancer therapy and recurrence. Triple-negative breast cancer (TNBC) is a subtype that responds poorly to therapy, making it a significant global health issue. Quercetin (QC) has been shown to affect CSC viability, but its low bioavailability limits its clinical use. This study aims to increase the effectiveness of QC in inhibiting CSC generation by using solid lipid nanoparticles (SLNs) in MDA-MB231 cells. MATERIALS AND METHODS: After treating MCF-7 and MDA-MB231 cells with 18.9 µM and 13.4 µM of QC and QC-SLN for 48 h, respectively, cell viability, migration, sphere formation, protein expression of ß-catenin, p-Smad 2 and 3, and gene expression of EMT and CSC markers were evaluated. RESULTS: The QC-SLN with particle size of 154 nm, zeta potential of -27.7 mV, and encapsulation efficacy of 99.6% was found to be the most effective. Compared to QC, QC-SLN significantly reduced cell viability, migration, sphere formation, protein expression of ß-catenin and p-Smad 2 and 3, and gene expression of CD44, zinc finger E-box binding homeobox 1 (ZEB1), vimentin, while increasing the gene expression of E-cadherin. CONCLUSIONS: Our findings demonstrate that SLNs improve the cytotoxic effect of QC in MDA-MB231 cells by increasing its bioavailability and inhibiting epithelial-mesenchymal transition (EMT), thereby effectively inhibiting CSC generation. Therefore, SLNs could be a promising new treatment for TNBC, but more in vivo studies are needed to confirm their efficacy.

What We Need to Know about Liposomes as Drug Nanocarriers: An Updated Review.

Liposomes have been attracted considerable attention as phospholipid spherical vesicles, over the past 40 years. These lipid vesicles are valued in biomedical application due to their ability to carry both hydrophobic and hydrophilic agents, high biocompatibility and biodegradability. Various methods have been used for the synthesis of liposomes, so far and numerous modifications have been performed to introduce liposomes with different characteristics like surface charge, size, number of their layers, and length of circulation in biological fluids. This article provides an overview of the significant advances in synthesis of liposomes via active or passive drug loading methods, as well as describes some strategies developed to fabricate their targeted formulations to overcome limitations of the "first-generation" liposomes.

Functionalized liposomes as drug nanocarriers for active targeted cancer therapy: a systematic review.

Cancer is a broad term used to describe a group of diseases that have more than 270 types. Today, due to the suffering of patients from the side effects of existing methods in the treatment of cancer such as chemotherapy and radiotherapy, the employment of targeted methods in the treatment of this disease has been received much consideration. In recent years, nanoparticles have revolutionized in the treatment of many diseases such as cancer. Among these nanoparticles, liposomes are more considerable. Active targeted liposomes show an important role in the selective action of the drug on cancer cells. Until now, a variety of anti-cancer agents have been reported for targeted delivery to cancer cells using liposomes. The results of in vitro and studies in vivo have been shown that selective action of the targeted liposomes is increased with reduced side effects and toxicity compared with free drugs or non-targeted liposomes. This systematic review expresses the reports of this type of drug delivery system. Search terms were searched through several online databases including PubMed, Scopus, and Science Direct from 1990 to 2019 and the quality evaluation was performed. Out of 11,676 published articles, 196 articles met the inclusion criteria. The current report reviews developments in the liposomes targeted with aptamer, transferrin, folate, and monoclonal antibodies.

Novel and efficient method for loading aptamer-conjugated liposomes with arsenic trioxide for targeting cancer cells.

Although the therapeutic effect of liposomal arsenic trioxide arsenic trioxide (ATO) in the treatment of solid tumours has been confirmed, its dose-limiting loading is a challenging issue. To solve the problems in the preparation of liposomal ATO, different loading strategies were evaluated and compared. In addition, liposomes decorated with anti-nucleolin aptamers were developed as a novel formulation for targeted delivery with high loading efficiency and sustained releasing property in order to treat solid tumours. The liposomes were prepared by a thin-film method exploiting the passive loading strategy of Co(II) hydrogen arsenite (CHA). The structural characteristics of the liposomes were also investigated by Fourier transform infra-red spectroscopy (FT-IR), dynamic light scattering (DLS), zeta potentiometry, field emission scanning electron microscopy (FESEM), and Energy Dispersive X-ray Diffraction (EDX) techniques. To evaluate the potential cytotoxicity of this liposomal drug vehicle in vitro, MTT assay was performed on HT-29 cancer cell line. The results showed that the synthesised liposomes loaded with CHA exhibited high entrapment efficiency (77%). MTT assays showed a significant difference between the percentage of viable cells when HT -29 cells were treated with free ATO and liposomal formulation which can be corresponded to the sustained release of the drug from the liposomes. The results of this study may lead to a promising strategy for the effective treatment of solid tumours.

An ultra-sensitive optical aptasensor based on gold nanoparticles/poly vinyl alcohol hydrogel as acceptor/emitter pair for fluorometric detection of digoxin with on/off/on strategy.

A novel nanobiosensor was prepared by aptamer and gold nanoparticles conjugate in poly vinyl alcohol hydrogel for sensitive detection of digoxin in human plasma samples. The developed nanobiosensor was characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering instrument. In this sensor the hydrogel acted as a fluorescent probe. The fluorescence intensity of the hydrogel was quenched by aptamer stabilized gold nanoparticles as energy acceptor. Upon addition of digoxin, the aptamer/drug complex was formed and the fluorescence of the hydrogel was restored because of destabilization and aggregation of gold nanoparticles in the presence of salt. The affecting parameters on the nanobiosensor performance were assessed and under the optimized conditions the external and in plasma calibration curves were linear in the 10-1000 ng L-1 digoxin concentration range with detection limits of 2.9 and 3.1 ng L-1, respectively. The relative standard deviations for 5 replicate determinations of 50, 250, and 500 ng L-1 of digoxin, were 7.3, 5.1, and 3.8%, respectively. This nanofluoroprobe was successfully applied for determination of digoxin in spiked plasma samples without any pretreatment procedure.

Hyperglycemia-induced oxidative stress in isolated proximal tubules of mouse: the in vitro effects of myricitrin and its solid lipid nanoparticle.

CONTEXT: The hyperglycemia (Hyper) induces oxidative stress in kidney tubular cells. Myricitrin (Myr) has an antioxidant effect along with low bioavailability. OBJECTIVE: The present research investigated the effects of Myr and its solid lipid nanoparticles (SLN) on isolated proximal tubules exposed to the hyperglycemic condition. MATERIALS AND METHODS: In this experimental study, the proximal tubules of mice were dissected by the microdissection method and the tubules were prepared for experimental or Real Time-PCR measurement. RESULTS: The malondialdehyde level, transforming growth factor-ß, nuclear factor kappa B and Bax genes expression increased in Hyper and decreased in Hyper + Myr and its SLN-treated groups compared to Hyper. Superoxide dismutase, total antioxidant capacity, the viability of proximal tubules and Bcl-2 gene expression decreased in untreated Hyper and increased in all treatment groups compared to Hyper. CONCLUSION: The hyperglycemia-induced oxidative disorder, inflammation and apoptosis in proximal tubules and that administrating Myr and its SLN improved them.

A novel strategy for detection of small molecules based on aptamer/gold nanoparticles/graphitic carbon nitride nanosheets as fluorescent biosensor.

Herein, a novel ultrasensitive strategy has been developed by designing a label free fluorescent nano-aptasensor for monitoring of small moecules in human plasma. In this nano-aptasensor, graphitic carbon nitride nanosheets were used as fluorescent probe. The fluorescence intensity of the probe was decreased by interaction between graphitic carbon nitride nanosheets and label-free aptamer/gold nanoparticles conjugate, via Fluorescence resonance energy transfer mechanism. Upon addition of the analyte, the fluorescence of graphitic carbon nitride nanosheets was restored due to the aptamer/analyte interaction, and the aggregation of gold nanoparticles in the presence of salt. The influence of various factors on sensing method was investigated, and under the approved conditions, the fluorescence signal showed a linear relation with Digoxin concentration in the range of 10-500 ng L-1 with limit of detection down to 3.2 ng L-1 relative standard deviations for 25, 100 and 500 ng L-1 of analyte concentrations were 2.6, 4.0 and 6.5%, respectively. This strategy provided a simple, rapid, cost effective and reproducible experimental model, with successful application for determination of Digoxin in plasma samples without any pretreatment steps.

Designing of a pH-Triggered Carbopol®/HPMC In Situ Gel for Ocular Delivery of Dorzolamide HCl: In Vitro, In Vivo, and Ex Vivo Evaluation.

Dorzolamide HCl (DRZ) ophthalmic drop is one of the most common glaucoma medications which rapidly eliminates after instillation leading to short residence time of the drug on cornea. The purpose of the present study is to develop a pH-triggered in situ gel system for ophthalmic delivery of DRZ for treatment of ocular hypertension. In this study, a 32 full factorial design was used for preparation of in situ gel formulations using different levels of Carbopol® and hydroxyl propyl methyl cellulose (HPMC). Rheological behavior, in vitro drug release, ex vivo corneal permeability, and IOP-lowering activity were investigated. DRZ solution (2% w/v) containing of 0.1% (w/v) Carbopol® and 0.1% (w/v) HPMC was selected as the optimal formulation considering its free flow under non-physiological conditions (initial pH and 25 ± 2°C) and transition to appropriate gel form under physiological circumstance (pH 7.4 and 34°C). This in situ gel presented the mucoadhesive property. Ex vivo corneal permeability of this combined solution was similar to those of DRZ solution. The developed formulation compared to the marketed drop (Biosopt®) and DRZ 2% solution had a better performance in intraocular pressure activity. The efficiency and long duration of IOP reduction could be due to the prolonged residence time of the in situ gel. The presence of Carbopol® as a pH triggered and mucoadhesive polymer causes to attach to the ocular mucosal surface for a long term.

Evaluation of the Protoscolicidal Effects of Albendazole and Albendazole Loaded Solid Lipid Nanoparticles.

BACKGROUND: Protoscolex plays an important role in the development of hydatid cyst. Albendazole is one of the most effectual protoscolicidal agents for averting the reappearance of this disease, nonetheless, its low solubility and its low intestinal absorption necessitates the presence of a drug carrier to enhance its efficacy. In this study, the effect of albendazole and its nano-form on protoscolices in cultured media and in vivo was evaluated. METHODS: Microemulsion method was used to prepare the Solid lipid nanoparticles (SLNs) containing albendazole. Infected livers were collected from the Slaughterhouse of Ahvaz, Khuzestan in 2017. The protoscolices were stored in RPMI 1640 for one week, and their survival under the influence of albendazole and nano-albendazole on days 3 and 7 at concentrations of 250 and 500µg / ml was investigated. The live protoscolices exposed on day 3 at a concentration of 250 µg/ml were injected to mice for evaluation of pathogenicity. Three months later, after autopsy of the mice, the pathogenicity was evaluated. RESULTS: Protoscolicidal efficacy was highest in both concentrations on day 7 for albendazole and on day 5 for nano-albendazole. Following the autopsy of the mice, cyst growth was reported in all mice, and only two mice from the albandazole loaded SLNs group did not have any cyst. CONCLUSION: Albendazole loaded SLNs showed a higher protoscolicidal property than the free form of this drug; therefore, the use of nano-formulation of this drug is recommended to prevent the onset of this disease.

New folate receptor targeted nano liposomes for delivery of 5-fluorouracil to cancer cells: Strong implication for enhanced potency and safety.

We previously showed that folate liposomes of 5FU made from Dipalmitoylphosphatidylcholine (DPPC) induced cell death in HT-29 and HeLa cells more potently than bulk 5FU. Also, a primary 5FU liposomal formulation with phosphatidyl choline (PC) exhibited higher cytotoxicity in murine colon cancer cells. In the present study, optimization of 5FU PC liposome, mechanism of cell death induction in human cancer cell lines and its safety along with other assays have been employed for targeted PC liposomes of 5FU. Liposomes were prepared using thin layer method and optimization of preparation was assessed using central composite design (CCD) of response surface methodology (RSM). Folic acid (FA) was employed as the targeting ligand. Morphology of 5FU loaded liposomes and changes in their thermal behavior were assessed by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC), respectively. In vitro cytotoxicity was explored using MTT assay in HT-29, Caco-2, HeLa and MCF-7 cell lines. Cytotoxicity mechanism of the targeted delivery system was searched through the evaluation of reactive oxygen species (ROS) overproduction, mitochondrial membrane potential (∆Ψm), the release of cytochrome c, the activity of caspase 3/7 and apoptosis and necrosis rate. Liposomes were spherical in shape and 5FU was successfully encapsulated into liposomes rather in an amorphous state. Our interesting results showed that in HT-29 cells targeted liposomes triggered the mitochondrial apoptotic pathway by decreasing the mitochondrial membrane potential, releasing of cytochrome c and promoting the substantial activity of caspase 3/7. In HeLa cells, however, targeted liposomes particularly activated necrosis pathway through the overproduction of ROS. Folate-liposomal 5FU showed significantly higher antitumor efficiency compared to free drug. The results of this study offer new prospects for cancer therapy with reducing systemic drug exposure and associated toxicities.

Antioxidant, anti-apoptotic, and protective effects of myricitrin and its solid lipid nanoparticle on streptozotocin-nicotinamide-induced diabetic nephropathy in type 2 diabetic male mice.

OBJECTIVES: The present study evaluates the protective effects of myricitrin and its solid lipid nanoparticle (SLN) on diabetic nephropathy (DN) induced by streptozotocin-nicotinamide (STZ-NA) in mice. MATERIALS AND METHODS: In this experimental study, 108 adult male NMRI mice were divided into 9 groups: control, vehicle, diabetes, diabetes + myricitrin 1, 3, and 10 mg/kg and, diabetes + SLN containing myricitrin 1, 3, and 10 mg/kg. After the experimental period, the plasma and tissue samples were collected for experimental, histopathological, real-time PCR and apoptosis assessments. RESULTS: Total antioxidant capacity, catalase, glomerular filtration rate, plasma level of albumin, urine (BUN) and, creatinine (Cr) levels decreased, and the kidney weight, intake/output, malondialdehyde, plasma level of BUN and Cr, urine level of sodium, potassium, albumin and glucose, fractional excretions of sodium and potassium, transforming growth factor-ß (TGF-ß) and nuclear factor kappa B (NF-κB) gene expression, red blood cell accumulation and infiltration of inflammatory cells, and kidney apoptosis increased in untreated diabetic mice compared to the control group, and administration of myricitrin and its SLN recovered all of these changes. CONCLUSION: Ultimately, myricitrin and its SLN administration improved DN changes by reducing oxidative stress and increasing antioxidant enzymes level, and these effects were more prominent in the SLN-administered mice.

The Effect of Preoperative Zintoma Capsule on Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy.

BACKGROUND: Postoperative nausea and vomiting (PONV), as one of the complications after laparoscopic cholecystectomy, occurs in over 40% - 77% of cases. Considering the numerous complications of synthetic drugs, there is a growing tendency towards the use of herbal medicines due to their unique features. Ginger root is one of the herbal compounds effective on nausea and vomiting. OBJECTIVES: The aim of this study was to evaluate the effect of preoperative Zintoma capsules on PONV after laparoscopic cholecystectomy. METHODS: In this quasi-experimental study, 130 eligible patients were randomly assigned to intervention (n = 65) and control (n = 65) groups using the four-block method. The intervention group received two capsules of 500 mg and one of 250 mg Zintoma. The control group received three placebo capsules. The severity of patients' PONV was recorded at 0, 2, 6, 12, and 24 hours after surgery using a checklist and a standard VAS instrument. Data were analyzed using t-test, Chi-square test, and LSD Post Hoc test (ANOVA) in SPSS 19. RESULTS: The severity of PONV and vomiting was significantly different between the two groups (P = 0.001) at the above time points. The mean severity of nausea (by VAS) changed in the intervention group from 7.92 ± 1.28 to 0.33 ± 0.67 and in the control group from 8.00 ± 1.20 to 2.11 ± 1.55. The postoperative vomiting was less frequent in the group receiving the Zintoma capsules. The postoperative use of chemical anti-vomiting and nausea drugs was significantly lower in the intervention group than in the placebo group (P = 0.001). CONCLUSIONS: Zintoma capsules can be used as a supportive treatment in the prevention of nausea and vomiting by reducing the incidence rate of PONV.

A mechanistic study of the effect of transferrin conjugation on cytotoxicity of targeted liposomes.

This study was performed to prepare 5-fluorouracil (5FU) containing targeted liposomes for the safety and efficacy enhancement. Liposomes were prepared using thin layer method and transferrin (Tf) was employed as the targeting ligand. Morphology of 5FU-loaded liposomes was assessed by transmission electron microscopy (TEM). The in vitro cytotoxicity was investigated via MTT assay on HT-29, CT26 and fibroblast cells. Mitochondrial membrane and cell death evaluations were also investigated. Resulted showed that the encapsulation efficiency (EE%) and particle size of the liposomes were 40.12% and 130 nm, respectively. TEM image implied that liposomes were spherical in shape. In cancer cells, targeted liposomes triggered the mitochondrial apoptotic pathway by lower production of reactive oxygen species (ROS) (63.58 vs 84.95 fluorescence intensity), reduced mitochondrial membrane potential and releasing of cytochrome c (68.66 vs 51.13 ng/mL). The results of this study indicated that Tf-targeted 5FU liposomes can be employed as promising nanocarrier for the delivery of drugs to cancer cells.

A novel 5-Fluorouracil targeted delivery to colon cancer using folic acid conjugated liposomes.

The aim of this study was to develop and characterize 5-Fluorouracil (5FU) containing targeted liposomes in order to enhance the efficacy and safety of the drug. Folic acid (FA) was used as a targeting ligand. The in vitro cytotoxicity of formulation against HT-29, Caco-2, CT26, HeLa and MCF-7 cell lines was evaluated using MTT assay. Mechanism of cell death induced by targeted liposomes was further investigated via the production of reactive oxygen species (ROS), change in mitochondrial membrane potential (ΔΨm), release of cytochrome c and activity of caspase 3/7. The in vivo tumor inhibition study was also performed after administration of drug and targeted 5FU liposome. The encapsulation efficiency (EE%) of the optimized formulation was 39.71%. Particle size of liposomes was around 174 nm and the nanoparticles were found to be spherical in shape. Differential Scanning Calorimetry (DSC) results indicated that the drug remained in an amorphous state in liposomes. According to the MTT results, targeted liposomes exhibited higher cytotoxicity than 5FU and liposomal 5FU. Targeted liposomes were found to trigger necrosis in HT-29 cells; while, in HeLa cells, targeted liposomes activated apoptotic pathway by collapse of ΔΨm, increased activity of cytochrome c as well as caspases activity. in vivo results showed that targeted liposomes reduced tumor volume significantly in comparison with 5FU (169.00 mm3 tumor volume vs 326.40 mm3). From these findings, it can be concluded that folic acid targeted liposomes may provide a new platform for selective delivery of drugs to cancer cells.

A novel micro-extraction strategy for extraction of bisphosphonates from biological fluids using zirconia nanoparticles coupled with spectrofluorimetry and high performance liquid chromatography.

Extraction of bisphosphonates from biological fluids is important and time consuming step in sample preparation procedure. This paper describes a simple and green sample preparation technique for dispersive micro solid phase extraction (DMSPE) of alendronate sodium (ALS) from urine and serum samples prior to direct spectrofluorimetry (DSFL) and high performance liquid chromatography with fluorescence detection (HPLC-FLD), respectively. The DMSPE strategy is based on the selective chemisorption of ALS on zirconia nanoparticles (ZNPs) as an adsorbent followed by derivatization of the eluted analyte using o-phthalaldehyde (OPA) in the presence of 2-mercaptoethanol (2ME) at basic medium to form fluorescent species. The chemical and instrumental influencing parameters on DMSPE and measuring methods were optimized for the efficient extraction and determination of ALS. The presented methods were capable of extracting ALS from human urine and serum samples and determining over the wide ranges of 5-1000 and 5-2500 µg L-1 with limits of detection (LOD) of 1.5 and 1.4 µg L-1 for DSFL and HPLC methods, respectively. The relative recoveries for the three spiked standard levels of ALS in urine and serum samples ranged from 89.0% to 107.0%, and the intra-day relative standard deviations (%RSDs) were in the range of 2.9-7.9%.

Solid Lipid Nanoparticles of Myricitrin Have Antioxidant and Antidiabetic Effects on Streptozotocin-Nicotinamide-Induced Diabetic Model and Myotube Cell of Male Mouse.

Type 2 diabetes mellitus (T2DM) may occur via oxidative stress. Myricitrin is a plant-derived antioxidant, and its solid lipid nanoparticle (SLN) may be more potent. Hence, the present study was conducted to evaluate the effects of myricitrin SLN on streptozotocin-nicotinamide- (STZ-NA-) induced T2DM of the mouse and hyperglycemic myotube. In this experimental study, cold homogenization method was used to prepare SLN. Then, 120 adult male NMRI mice were divided into 7 groups: control, vehicle, diabetes (received STZ 65 mg/kg 15 min after injected NA 120 mg/kg), diabetes + SLN containing myricitrin 1, 3, and 10 mg/kg, and diabetes + metformin. For in vitro study, myoblast (C2C12) cell line was cultured and divided into 6 groups (n = 3): control, hyperglycemia, hyperglycemia + SLN containing myricitrin 1, 3, and, 10 µM, and hyperglycemia + metformin. After the last nanoparticle treatment, plasma samples, pancreas and muscle tissues, and myotubes were taken for experimental assessments. Diabetes increased lipid peroxidation and reduced antioxidant defense along with the hyperglycemia, insulin resistance, and pancreas apoptosis. Hyperglycemia induced oxidative stress, antioxidant impairment, and cellular apoptosis. Myricitrin SLN improved diabetes and hyperglycemia complications in the in vivo and in vitro studies. Therefore, SLN of myricitrin showed antioxidant, antidiabetic, and antiapoptotic effects in the mouse and myotube cells.