Biomedical applications of PLGA nanoparticles in nanomedicine: advances in drug delivery systems and cancer therapy.

INTRODUCTION: During the last decades, the ever-increasing proportion of patients with cancer has been led to serious concerns worldwide. Therefore, the development and use of novel pharmaceuticals, like nanoparticles (NPs)-based drug delivery systems (DDSs), can be potentially effective in cancer therapy. AREA COVERED: Poly lactic-co-glycolic acid (PLGA) NPs, as a kind of bioavailable, biocompatible, and biodegradable polymers, have approved by the Food and Drug Administration (FDA) for some biomedical and pharmaceutical applications. PLGA is comprised of lactic acid (LA) and glycolic acid (GA) and their ratio could be controlled during various syntheses and preparation approaches. LA/GA ratio determines the stability and degradation time of PLGA; lower content of GA results in fast degradation. There are several approaches for preparing PLGA NPs that can affect their various aspects, such as size, solubility, stability, drug loading, pharmacokinetics, and pharmacodynamics, and so on. EXPERT OPINION: These NPs have indicated the controlled and sustained drug release in the cancer site and can use in passive and active (via surface modification) DDSs. This review aims to provide an overview of PLGA NPs, their preparation approach and physicochemical aspects, drug release mechanism and the cellular fate, DDSs for efficient cancer therapy, and status in the pharmaceutical industry and nanomedicine.

Smart chitosan-PLGA nanocarriers functionalized with surface folic acid ligands against lung cancer cells.

Lung cancer is the second most prevalent and first killer cancer worldwide, and conventional approaches do not have enough ability to suppress it. Therefore, a novel targeted chitosan (CS)-poly lactic-co-glycolic acid (PLGA)-folic acid (FA) nanocarrier was developed for delivery of sorafenib (Sor) to lung cancer cells. The nanocarrier (CPSF) had a size of 30-40 nm with globular shapes. Surface charge and drug content of CPSF were ascertained at about 1.1 mV and 15 %, respectively. Controlled (4 % within 2 h) and pH-sensitive (18 % within 2 h at pH = 5.0) Sor release were observed for the nanocarrier. The MTT assay demonstrated a cell viability of 13 % after 24 h treatment with 400 nM CPSF in A549 cancer cells while it was 78 % in MSC normal cells. The qRT-PCR revealed >8 folds and 11 folds increase for Caspase9 and P53 genes after 5 h treatment with 100 nM (IC50) CPSF; but a reduction of 5 folds was observed for the Bcl2 gene. Besides, 57 % and 20 % apoptosis were attained in cell cycle arrest and apoptosis assays for CPSF, respectively. CPF indicated about 88 % internalization in cancer cells. These data prove that CPSF is a promising nanodelivery system for lung cancer suppression.

SNAP-25 gene variations and attention-deficit hyperactivity disorder in Iranian population.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition of childhood characterized by persistent symptoms of hyperactivity, inattention, and impulsivity. The objective of this study was to investigate the association of synaptosomal-associated protein of 25 kDa (SNAP-25) gene variants with ADHD. METHODS: A case-control study with a total of 150 children with ADHD (mean age 9.61; range 6-16; gender ratio 105m/45f) and 150 normal children (mean age 10.02; range 6-16; gender ratio 98m/52f) was conducted. Genomic DNA was extracted from peripheral blood of all samples and SNPs rs78428954 and rs3746544 located in SNAP-25 gene were genotyped. RESULTS: Our analysis indicated that there is no significant association between none of studied variants in SNAP-25 and ADHD. DISCUSSION: To our knowledge, it is the first report of SNAP-25 genotyping in Iranian patients with ADHD. Further investigations with larger populations are needed in order to clarify the exact role of SNAP-25 variations in susceptibility to ADHD.

Protective effects of forced exercise against nicotine-induced anxiety, depression and cognition impairment in rat.

BACKGROUND: Nicotine is one of the psychostimulant agents displaying parasympathomimetic activity; the chronic neurochemical and behavioral effects of nicotine remain unclear. Exercise lowers stress and anxiety and can act as a non-pharmacologic neuroprotective agent. In this study, the protective effects of exercise in nicotine withdrawal syndrome-induced anxiety, depression, and cognition impairment were investigated. METHODS: Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control and received normal saline (0.2 mL/rat, i.p.) for 30 days, whereas group 2 (as positive control) received nicotine (6 mg/kg/day, s.c.) for the first 15 days. Groups 4, 5, and 6 were treated with nicotine (6 mg/kg/day, s.c.) for the first 15 days and then were treated with forced exercise, bupropion (20 mg/kg/day, i.p.), or a combination of the two for the following 15 days. Between day 25 and day 30, Morris water maze was used to evaluate spatial learning and memory. From days 31 to 35, the elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were used to investigate the level of anxiety and depression in the subjects. RESULTS: Nicotine-dependent animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM, and TST, which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. CONCLUSIONS: Forced exercise, bupropion, or their combination can attenuate nicotine cessation-induced anxiety, depression, and motor activity in the mentioned behavioral assay. We conclude that forced exercise can protect the brain against nicotine withdrawal-induced anxiety, depression, and cognitive alteration.

Distal femoral osteotomy in genovalgum: internal fixation with blade plate versus casting.

BACKGROUND: To compare the results of two different ways of distal femoral osteotomy stabilization in patients suffering from genuvalgum: internal fixation with plate, and casting. METHODS: In a non-randomized prospective study, after distal femoral osteotomy with the zigzag method, patients were divided into two groups: long leg casting, and internal fixation with blade plate. For all patients, questionnaires were filled to obtain data. Information such as range of motion, tibiofemoral anatomical angle and complications were recorded. RESULTS: 38 knees with valgus deformity underwent distal femoral supracondylar osteotomy. (8 with plaster cast and 30 with internal fixation using a blade plate). Preoperative range of motion was 129±6° and six months later it was 120±14°. The preoperative tibiofemoral angle was 32±6°; postoperative tibiofemoral angles were 3±3°, 6±2°, and 7±3° just after operation, six months, and two years later, respectively. Although this angle was greater among the group stabilized with a cast, this difference was not statistically significant. In postoperative complications, over-correction was found in five, recorvatom deformity in one, knee stiffness in three and superficial wound infection was recorded in three knees. CONCLUSIONS: There is no prominent difference in final range of motion and alignment whether fixation is done with casting or internal fixation. However, the complication rate seems higher in the casting method.

Accuracy of lachman and anterior drawer tests for anterior cruciate ligament injuries.

BACKGROUND: The knee joint is prone to injury because of its complexity and weight-bearing function. Anterior cruciate ligament (ACL) ruptures happen in young and physically active population and can result in instability, meniscal tears, and articular cartilage damage. The aim of this study is to evaluate the accuracy of Lachman and anterior drawer tests in ACL injury in compare with arthroscopy. METHODS: In a descriptive, analytical study from 2009 to 2013, 653 patients who were suspected to have ACL rapture were entered the study. Statistical analysis was performed by the usage of SPSS 16. Multiple comparison procedures were performed for comparing data between clinical examination and arthroscopic findings and their relation with age and sex. RESULTS: Mean age of patients was 28.3±7.58 years (range from 16 to 68 years). From 428 patients, 41.2% (175 patients) were between 26 and 35, 38.8% (165 ones) between 15 and 25 and 20% (85 patients) out of 36 years. 414 patients were male (97.2%) and 12 were female (2.8%). Sensitivity of anterior drawer test was 94.4% and sensitivity of Lachman test was 93.5%. CONCLUSION: The diagnosis of the ACL injury and the decision to reconstruct ACL could be reliably made with regards to the anterior drawer and Lachman tests result. The tests did not have privilege to each other. The test accuracy increased considerably under anesthesia especially in women.