Combination chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model.

The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood-brain-barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood-brain-barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs + P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6% of the NPs were concentrated in the brain after 48 h. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.

Bone Healing Monitoring in Bone Lengthening Using Bioimpedance.

The most common technique of orthopedic surgical procedure for the correction of deformities is bone lengthening by "distraction osteogenesis," which requires periodic and ongoing bone assessment following surgery. Bone impedance is a noninvasive, quantitative method of assessing bone fracture healing. The purpose of this study was to monitor bone healing and determine when fixation devices should be removed. The left tibia of eight male New Zealand white rabbits (2.4 ± 0.4 kg) undergoing osteotomy was attached with a mini-external fixator. The bone length was increased by 1 cm one week after surgery by distracting it 1 mm per day. Before and after osteotomy, as well as every week after, bone impedance was measured in seven frequency ranges using an EVAL-AD5933EBZ board. Three orthopedic surgeons analyzed the radiographs using the Radiographic Union Scale for Tibial (RUST) score. The Kappa Fleiss coefficient was used to determine surgeon agreement, and the Spearman rank correlation coefficient was used to find out the relationship between impedance measurements and RUST scores. Finally, the device removal time was calculated by comparing the bone impedance to the preosteotomy impedance. The agreement of three orthopedic surgeons on radiographs had a Fleiss' Kappa coefficient of 49%, indicating a moderate level of agreement. The Spearman rank correlation coefficient was 0.43, indicating that impedance and radiographic techniques have a direct relationship. Impedance is expected to be used to monitor fractured or lengthened bones in a noninvasive, low-cost, portable, and straightforward manner. Furthermore, when used in conjunction with other qualitative methods such as radiography, impedance can be useful in determining the precise time of device removal.

Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage.

Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-п content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-п in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P≤0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P≤0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and decreases their numbers. Enrofloxacin use in growing lambs even at recommended therapeutic dose is not completely safe on articular cartilage. Moreover, higher doses of enrofloxacin induce severe changes in lamb articular cartilage.

The proliferation study of hips cell-derived neuronal progenitors on poly-caprolactone scaffold.

INTRODUCTION: The native inability of nervous system to regenerate, encourage researchers to consider neural tissue engineering as a potential treatment for spinal cord injuries. Considering the suitable characteristics of induced pluripotent stem cells (iPSCs) for tissue regeneration applications, in this study we investigated the adhesion, viability and proliferation of neural progenitors (derived from human iPSCs) on aligned poly-caprolactone (PCL) nanofibers. METHODS: Aligned poly-caprolactone nanofibrous scaffold was fabricated by electrospinning and characterized by scanning electron microscopy (SEM). Through neural induction, neural progenitor cells were derived from induced pluripotent stem cells. After cell seeding on the scaffolds, their proliferation was investigated on different days of culture. RESULTS: According to the SEM micrographs, the electrospun PCL scaffolds were aligned along with uniformed morphology. Evaluation of adhesion and viability of neural progenitor cells on plate (control) and PCL scaffold illustrated increasing trends in proliferation but this rate was higher in scaffold group. The statistical analyses confirmed significant differences between groups on 36h and 48h. DISCUSSION: Evaluation of cell proliferation along with morphological assessments, staining and SEM finding suggested biocompatibility of the PCL scaffolds and suitability of the combination of the mentioned scaffold and human iPS cells for neural regeneration.

Comparison of the prophylactic effect of silymarin and deferoxamine on iron overload-induced hepatotoxicity in rat.

In pathologic conditions or poisoning states, iron overload can affect different tissues including liver. In this study, the prophylactic effect of deferoxamine and silymarin was compared in decreasing experimental iron-overload-induced hepatotoxicity in rats. The study was done in six groups of rats, which received drugs q2 days for 2 weeks. The rats in groups 1 to 6 received drugs, respectively: normal saline, iron dextran, iron dextran + deferoxamine (intraperitoneally), iron dextran + silymarin (orally), iron dextran + silymarin (intraperitoneally), and iron dextran + deferoxamine (intraperitoneally) + silymarin (intraperitoneally). At the end of the study, blood was collected, and serum was separated for laboratory tests. The liver of rats was separated for iron measuring and tissue processing. The serum iron concentration and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were determined. The numbers of necrotic hepatocytes were counted as quantity index tissue injury in light microscopic examination. The mean of serum and liver iron in group 2 was significantly greater than group 1. Liver iron was significantly decreased in other groups except group 4. Also serum iron was decreased in groups 3 to 6 compared to group 2 (nearly 400%). ALT activity in group 3 and AST activity in group 5 were significantly lesser than in other groups. The mean of necrotic hepatocytes in group 2 was significantly increased in comparison to group 1. This elevation was significantly prevented by deferoxamine and silymarin. The result of the present study shows that silymarin has a protective effect similar to deferoxamine on iron overload-induced hepatotoxicity.