RESUMEN
Background: Drug delivery systems have been designed to achieve targeted delivery and control the release rate of the drugs. A serious challenge associated with drug delivery systems is the presence of the blood-brain barrier which limits drugs penetration. In the current study, the effects of cisplatin nanoparticles on A172 brain cancer cell line were investigated. Methods: Cisplatin nanoparticles were produced by miniemulsion polymerization technique and their properties were evaluated. Drug release assay was performed to characterize the nanoparticles' properties. Here, we examined the effects of cisplatin nanoparticles and free form of cisplatin on A172 cancer cell line. MTT assay was performed for different concentrations of the drug. To measure the apoptosis rate in A172 cell line in the presence of cisplatin nanoparticles or its free from, Annexin V staining method was used. Results: Our results indicated that loading type of cisplatin was physical loading and only 4.7% of cisplatin was released after 68 h. Furthermore, MTT assay showed that cisplatin nanoparticles in all concentrations had more cytotoxic effects on the cells comparing with the free form of cisplatin and control groups. We also showed that cisplatin nanoparticles could increase apoptosis in cancer cells more than the drug in the free form by using flow cytometry technique. Conclusion: Overall, these findings proved that cisplatin loaded on poly (Butylcyanoacrylate) nanoparticles, was more efficient than the free form of cisplatin in treating A172 cancer cell line.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/farmacología , Enbucrilato/química , Nanopartículas/administración & dosificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Cisplatino/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Enbucrilato/administración & dosificación , Humanos , Nanopartículas/química , Polímeros/administración & dosificación , Polímeros/químicaRESUMEN
In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.