Drug delivery in glioblastoma therapy: a review on nanoparticles targeting MGMT-mediated resistance.

Introduction: Glioblastoma multiforme (GBM) is the deadliest type of brain cancer with poor response to the available therapies, mainly due to intrinsic resistance mechanisms. Chemotherapy is based on alkylating agents, but DNA-repair mechanisms can revert this cytotoxic effect. O-methylguanine-DNA methyltransferase (MGMT) protein is the primary mechanism for GBM resistance.

Nanocarriers Based on Gold Nanoparticles for Epigallocatechin Gallate Delivery in Cancer Cells.

Gold nanoparticles (AuNPs) are inorganic and biocompatible nanovehicles capable of conjugating biomolecules to enhance their efficacy in cancer treatment. The high and reactive surface area provides good advantages for conjugating active compounds. Two approaches were developed in this work to improve the Epigallocatechin-3-gallate (EGCG) antioxidant efficacy.

Transferrin Receptor-Targeted Nanocarriers: Overcoming Barriers to Treat Glioblastoma.

Glioblastoma multiforme (GBM) is the most common and lethal type of brain tumor, and the clinically available approaches for its treatment are not curative. Despite the intensive research, biological barriers such as the blood-brain barrier (BBB) and tumor cell membranes are major obstacles to developing novel effective therapies. Nanoparticles (NPs) have been explored as drug delivery systems (DDS) to improve GBM therapeutic strategies.

Molecular interactions between Vitamin B12 and membrane models: A biophysical study for new insights into the bioavailability of Vitamin.

Vitamin B12 (VB12) deficiency is one of the most common malnutrition problems worldwide and is related to its poor bioavailability. The lipid composition of cell membranes and molecule-cell membrane lipid interactions are major factors affecting the bioavailability of nutrients. So, the study of these interactions may allow predicting the behavior of VB12 at cellular membranes and the effects on its activity.

Doxorubicin and Varlitinib Delivery by Functionalized Gold Nanoparticles Against Human Pancreatic Adenocarcinoma.

The aim of this study was to develop drug delivery nanosystems based on pegylated gold nanoparticles (PEGAuNPs) for a combination against pancreatic cancer cells. Doxorubicin and varlitinib, an anthracycline and a tyrosine kinase inhibitor respectively, were conjugated with gold nanoparticles. The systems were characterized, after synthesis, regarding their size, stability and morphology.

Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the Co-Delivery of Temozolomide and O6-Benzylguanine.

Poly(d,l-lactic--glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms.

Biophysical interaction of temozolomide and its active metabolite with biomembrane models: The relevance of drug-membrane interaction for Glioblastoma Multiforme therapy.

Temozolomide (TMZ) is the first-line treatment for Glioblastoma Multiforme (GBM). After administration, TMZ is rapidly converted into its active metabolite (MTIC). However, its pharmacological activity is reduced due MTIC low bioavailability in the brain.

Development of Parvifloron D-loaded Smart Nanoparticles to Target Pancreatic Cancer.

Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, plants belonging to genus and their isolated compounds, such as Parvifloron D, were found to have cytotoxic and antiproliferative activities.

Gold Nanoparticles for Targeting Varlitinib to Human Pancreatic Cancer Cells.

Colloidal gold nanoparticles are targeting probes to improve varlitinib delivery into cancer cells. The nanoconjugates were designed by the bioconjugation of pegylated gold nanoparticles with varlitinib via carbodiimide-mediated cross-linking and characterized by infrared and X-ray photoelectron spectroscopy. The drug release response shows an initial delay and a complete drug release after 72 h is detected.

Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer's Disease.

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics.

Cellular uptake of PLGA nanoparticles targeted with anti-amyloid and anti-transferrin receptor antibodies for Alzheimer's disease treatment.

During the last few decades, relevant efforts have been reported to design nanocarriers for drug transport through the blood brain barrier (BBB). New drugs, such as peptide iAβ5, capable to inhibit the aggregates associated with Alzheimeŕs disease (AD) are being tested but the most frequent drawback is to reach the brain in the desired concentrations due to the low BBB permeability-surface area. Our approach, as a proof of concept to improve drug transport through the BBB, is based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles with surface functionalized with anti-transferrin receptor monoclonal antibody (OX26) and anti-Aβ (DE2B4) to deliver encapsulated iAβ5 into the brain.

Enhancing the efficiency of bortezomib conjugated to pegylated gold nanoparticles: an in vitro study on human pancreatic cancer cells and adenocarcinoma human lung alveolar basal epithelial cells.

Objectives: Gold nanoparticles have become promising vectors for cancer diagnosis and treatment. The present study investigates the effect of bortezomib (BTZ), a proteasome inhibitor, conjugated with pegylated gold nanoparticles (PEGAuNPs) in pancreatic and lung cancer cells.

Methods: Synthesized gold nanoparticles (PEGAuNPs) were conjugated with bortezomib antitumor drug.

The Health Care Revenue Cycle. Management in Brazil: Challenges that keep CEOs awaken.

Brazil's economic and political crisis had never been deeper, hardening the way companies deal on the market. Only those that are able to deal with tougher market conditions remain in the game, while facing increasingly difficult situations. A continuous rise in competition has shrunk prices and compressed margins, imposing necessary improvements to the way companies work in order to remain sustainable.

Functionalized gold nanoparticles improve afatinib delivery into cancer cells.

Objectives: A drug delivery system based on colloidal pegylated gold nanoparticles (PEGAuNPs) conjugated with the tyrosine kinase inhibitor afatinib was designed and tested for enhancing the drug activity against pancreatic and NSCLC cells.

Methods: PEGAuNPs were synthesized and characterized physicochemically. Confocal imaging was performed to evaluate the nanoparticle (NP) internalization in cancer cells.

Immunoliposomes doubly targeted to transferrin receptor and to α-synuclein.

Aim: The present study was designed to test the cellular uptake of PEGylated liposomes targeted to transferrin receptor and to α-synuclein by a cell model of the blood-brain barrier (BBB).

Materials & Methods: PEGylated immunoliposomes were prepared with anti-transferrin receptor OX26 and anti-α-synuclein LB509 antibodies to overcome the BBB in Parkinson's disease.

Results: The doubly targeted immunoliposomes bind to transferrin receptor and to α-synuclein protein, as assessed by ELISA assays.

Dual ligand immunoliposomes for drug delivery to the brain.

Drug delivery systems that can reach brain areas affected by amyloid deposits are still underdeveloped. We propose pegylated liposomes functionalized with two antibodies, the anti-transferrin receptor monoclonal antibody (OX26MAb) and the anti-amyloid beta peptide antibody (19B8MAb), as nanocarriers of drugs for Alzheimer's disease therapy. Two distinct conjugation methods are investigated.

PLGA nanoparticles as a platform for vitamin D-based cancer therapy.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were studied as drug delivery vehicles for calcitriol, the active form of vitamin D3. In vitro effects of calcitriol encapsulated in PLGA nanoparticles were evaluated with respect to free calcitriol on human pancreatic cell lines, S2-013 and hTERT-HPNE, and the lung cancer cell line A549. Encapsulated calcitriol retained its biological activity, reducing the cell growth.

Supramolecular nanoscale assemblies for cancer diagnosis and therapy.

Nanocarriers based on polymers, metals and lipids have been extensively developed for cancer therapy and diagnosis due to their ability to enhance drug accumulation in cancer cells and decrease undesired drug toxicity in healthy tissues. Overcoming multidrug resistance by designing proper drug nanocarriers will improve outcome of existing oncologic treatments such as chemotherapy and radiotherapy. In this article the relation between physicochemical properties and capacity of a nanosystem to deliver therapeutic agents into pathological sites is discussed.

Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach.

In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs).

The Potential Effect of Fluorinated Compounds in the Treatment of Alzheimer's Disease.

Drug development for neurodegenerative diseases such as Alzheimer's disease (AD) is a challenge, not only due to the cellular molecular mechanisms involved, but also because of the inherent difficulty of most molecules to cross the blood-brain-barrier (BBB). A promising approach to overcome these drawbacks is developing fluorinated molecules and supramolecular assemblies. This review focuses on the therapeutic potential of new fluorinated molecules, developed as active and selective agents for AD, to meet the desired pharmacokinetic/pharmacodynamic properties and BBB targeting.

Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells.

The aim of this study was to develop a drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles for an efficient and targeted action of the proteasome inhibitor bortezomib against pancreatic cancer cells. The PLGA nanoparticles were formulated with a poloxamer, and further surface-modified with transferrin for tumor targeting. The nanoparticles were characterized as polymer carriers of bortezomib, and the cellular uptake and growth inhibitory effects were evaluated in pancreatic cells.

Targeting nanoparticles across the blood-brain barrier with monoclonal antibodies.

Development of therapeutics for brain disorders is one of the more difficult challenges to be overcome by the scientific community due to the inability of most molecules to cross the blood-brain barrier (BBB). Antibody-conjugated nanoparticles are drug carriers that can be used to target encapsulated drugs to the brain endothelial cells and have proven to be very promising. They significantly improve the accumulation of the drug in pathological sites and decrease the undesirable side effect of drugs in healthy tissues.

Fluorinated beta-sheet breaker peptides.

The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease. We synthesized peptides containing fluorinated amino acids and studied their effect on the Aβ aggregation. The peptides were based on the sequence LVFFD, in which valine was substituted by either 4,4,4-trifluorovaline or 4-fluoroproline, or the phenylalanine at position 3 was replaced by 3,4,5-trifluorophenylalanine.

Enhancing proteasome-lnhibitor effect by functionalized gold nanoparticles.

Colloidal gold nanoparticles intensify the anticancer response of the drug bortezomib, a proteasome inhibitor. Polyethylene glycol-coated gold nanoparticles and the drug show a synergistic effect in reducing the cell viability of prostate cancer cell line Du145. It was observed a significant cell viability reduction with bortezomib concentrations as low as 4 nM.

Gold nanoparticle delivery-enhanced proteasome inhibitor effect in adenocarcinoma cells.

Background: Proteasome inhibition is a current therapeutic strategy used in the treatment of multiple myeloma. Drugs controlling proteasome activity are ideally suited for unidirectional manipulation of cellular pathways such as apoptosis. The first proteasome inhibitor approved in clinics was bortezomib.