Transfection of pulmonary cells by stable pDNA-polycationic hybrid nanostructured particles.

AIM: Cationically modified solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carriers and transfection agents for the pulmonary route. MATERIALS & METHODS: pDNA-loaded SLN were produced using glyceryl dibehenate or tristearate as matrix lipids and chitosan as surface charge modifier, and encapsulated by spray-drying in mannitol and trehalose microspheres. RESULTS: Nanoparticles of 200 nm, and zeta potential around +15 mV were produced. Electrophorectic analysis confirmed plasmid stability and integrity. The pDNA-loaded SLN were able to transfect the Calu-3 and A549 pulmonary cell lines, while showing low cytotoxicity. Microencapsulation of SLN yielded dry powders suitable for inhalation that protected pDNA from degradation. CONCLUSION: Microencapsulated SLN are a promising safe and effective carrier system for pulmonary gene delivery following pulmonary administration.

Gastrointestinal stromal tumours: an actualized overview

The gastrointestinal stromal tumour (GISTs), the most common mesenchymal neoplasm in the gastrointestinal tract, has been the subject of great interest in recent years in terms of prognosis, diagnosis and treatment. Its etiology is linked to the mutation of c-KIT and PDGFRA genes, although between 5 and 15% show no signs of such mutations. It is still diagnosed using immunohistochemical staining. The first line of treatment continues to be surgery, although advances in the molecular biology of GISTs are facilitating the development of new treatment strategies. Those that act by regulating tyrosine kinase activity are of particular interest. Drugs such as imatinib and sunitinib have improved the prognosis of these patients, although the development of resistance constitutes one of the main limitations of the treatment. The aim of this review is to present an up-to-date overview of the main etiopathogenic, diagnostic and therapeutic aspects of these tumours

No disponible

Last Advances in Nanocarriers-Based Drug Delivery Systems for Colorectal Cancer.

Colorectal cancer is the third most common type of cancer in both, men and women. The development of metastasis is very frequent, especially in patients with advanced stage, who require intensive chemotherapy that often results in poor response and significant morbidity. The undesirable effects of intensive chemotherapy on normal cells and the development of multidrug resistance are two of the main causes of treatment failure. Recent advances in nanotechnology allow to target cancer cells using cytotoxic drugs without affecting normal cells. Nanocarriers such as liposomes, polymeric nanoparticles and carbon nanotubes, among others, are able to improve drug distribution and bioavailability, cytotoxic concentration in the tumor mass and drug delivery to tumor tissue and, at the same time, reduce side effects. Current research studies are being conducted to develop new biomaterials that improve the characteristics of these nanomolecules. Several preclinical assays have disclosed the efficacy of nanotherapy in colon cancer, although further clinical trials will be necessary to demonstrate its efficacy. This review discusses the current status and the potential advantages of using nanocarrier-based drug delivery systems for colorectal cancer.

Application of nanotechnology in the treatment and diagnosis of gastrointestinal cancers: review of recent patents.

Gastrointestinal cancers remain one of the main causes of death in developed countries. The main obstacles to combating these diseases are the limitations of current diagnostic techniques and the low stability, availability, and/or specificity of pharmacological treatment. In recent years, nanotechnology has revolutionized many fields of medicine, including oncology. The association of chemotherapeutic agents with nanoparticles offers improvement in the solubility and stability of antitumor agents, avoidance of drug degradation, and reductions in therapeutic dose and toxicity, increasing drug levels in tumor tissue and decreasing them in healthy tissue. The use of specific molecules that drive nanoparticles to the tumor tissue represents a major advance in therapeutic specificity. In addition, the use of nanotechnology in contrast agents has yielded improvements in the diagnosis and the follow-up of tumors. These nanotechnologies have all been applied in gastrointestinal cancer treatment, first in vitro, and subsequently in vivo, with promising results reported in some clinical trials. A large number of patents have been generated by nanotechnology research over recent years. The objective of this paper is to review patents on the clinical use of nanoparticles for gastrointestinal cancer diagnosis and therapy and to offer an overview of the impact of nanotechnology on the management of this disease.

Signal transduction pathways involved in macrophage migration induced by peritoneal fluid chemotactic factors in stages I and II endometriosis.

OBJECTIVE: To explore the role of G-protein coupled signaling pathways in activation of macrophage migration in endometriosis stages I and II. DESIGN: Case controlled study. SETTING: University hospital. PATIENT(S): Fifteen patients undergoing laparoscopy for elective sterilization (n = 5) or for diagnosis of endometriosis stages I and II associated with infertility (n = 10). INTERVENTION(S): Peritoneal fluid samples were collected during laparoscopy. MAIN OUTCOME MEASURE(S): Macrophage migration induced by peritoneal fluid from patients with endometriosis stages I and II (PF SI-II) and potential G-protein coupled receptors and second messengers involved in macrophage activation. RESULT(S): Potential G-protein coupled receptors and second messengers involved in macrophage activation were evaluated after incubation of U-937 cells differentiated into macrophages with inhibitors of phospholipase A and C, adenylate cyclase, and protein kinase A and C. Macrophage chemotactic activity induced by PF SI-II was inhibited in the presence of a phospholipase C and A2 inhibitor (IC50= 30 microM) and after treatment with myristoylated protein kinase C peptide inhibitor (50 nM). An increase in inositol phosphate (IP3) was also observed in macrophages exposed to PF SI-II. Activation of multiple G-proteins in macrophages was examined after exposure of cells to PF SI-II in the presence and absence of Bordettela pertussis and cholera toxins. No effect on macrophage migration was observed. CONCLUSION(S): Macrophage chemotaxis induced by PF SI-II appears to involve activation of pertussis toxin-insensitive G-protein coupled receptors in macrophages. Our data suggest that these events lead to subsequent activation of phospholipases followed by generation of IP3 and potential mobilization of intracellular Ca2+. Subsequent phosphorylation of target proteins by protein kinase C may regulate the chemotactic responses. The adenylate cyclase pathway does not appear to play a role in this process.