ABSTRACT
This report is an integrated study to include the molecular simulation, physicochemical characterization and biological analysis of a paclitaxel-loaded PHBV nanoparticle that demonstrates uptake, release and cytotoxicity in cancer cell lines. Taking this nanoparticle one step closer to its use in a clinical setting, we demonstrate that it causes significant cell death in primary cultures of stage IIIc serous ovarian cancer cells isolated from six patients. Molecular simulations revealed a high affinity of paclitaxel for the water-polymer interface, thus the drug is delivered only when the polymer near it is degraded. The Fourier transform infrared spectroscopy suggests the formation of a short-lived crystalline phase, also observed in the CG simulations, and transmission electron microscopy revealed branched structures on the surface of particles, which disappeared after 4 days. Biological analyses indicated that these particles have a 48-h window of toxicity protection, allowing for the endocytosis of the particle by the cells; this finding was corroborated by confocal microscopy and flow cytometry. The low cost to synthesize PHBV using microorganisms and the potential chemical modifications of the polymer make it attractive for inexpensive, large-scale pharmaceutical production.
Subject(s)
Endometrial Neoplasms/drug therapy , Nanoparticles/toxicity , Ovarian Neoplasms/drug therapy , Paclitaxel/therapeutic use , Polyesters/toxicity , Cell Death/drug effects , Endometrial Neoplasms/pathology , Female , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , M Phase Cell Cycle Checkpoints/drug effects , Microscopy, Fluorescence , Nanoparticles/ultrastructure , Ovarian Neoplasms/pathology , Oxazines/metabolism , Paclitaxel/pharmacology , Particle Size , Spectroscopy, Fourier Transform Infrared , Static Electricity , Time Factors , Tumor Cells, Cultured , Water/chemistryABSTRACT
BACKGROUND: Two of each three women in their menopause present climacterical syndrome, showing frequently psychological symptoms, which is translated in diminution of the personal satisfaction, which generates the necessity of specialized attention. OBJECTIVE: To know the presence and frequency of psychological symptoms, before and after a psychotherapeutic process with a psychodynamic approach, in a group of women in their menopause. PATIENTS AND METHOD: The sample consisted of 41 women divided in two groups, with pre and post application of the survey of symptoms, group 1 received psychotherapy and group 2 did not, although it required it, for this reason it was considered the control. The psychotherapy consisted of 17 sessions and the used techniques most frequently were: confrontation, clarification and interpretation. RESULTS: Differences in the diminution as in the absence of symptoms were observed as much after the psychotherapeutic process. CONCLUSIONS: The psychoanalytic psychotherapy is functional in this type of patients for the diminution and in some cases the disappearance of psychological symptoms.
