Ophthalmic wild olive (ACEBUCHE) oil nanoemulsions exert oculoprotective effects against oxidative stress induced by arterial hypertension.

Oxidative stress plays a key role in several systemic and ocular diseases, including hypertensive eye diseases. In this context, we previously showed that oral administration of wild olive (acebuche, ACE) oil from Olea europaea var. sylvestris can counteract ocular damage secondary to arterial hypertension by modulating excess reactive oxygen species (ROS) produced by the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Therefore, this work describes the development of an ACE oil-based formulation for ocular administration as a local therapy to counteract hypertension-related oxidative damage. Specifically, ACE oil nanoemulsions (NEs) were successfully produced and characterized, exhibiting appropriate features for ophthalmic administration, including a nanometer size (<200 nm), moderate negative ZP, adequate osmolality and pH, and colloidal stability in biorelevant fluids. Likewise, the NEs presented a shear thinning behavior, especially convenient for ocular instillation. In vivo evaluation was performed through either intravitreal injection or topical ophthalmic administration in mice with hypertension induced via administration of Nω-nitro-L-arginine-methyl-ester (L-NAME). Both routes of administration reduced hypertensive morphological alterations and demonstrated a noticeable antioxidant effect thanks to the reduction of the activity/expression of NADPH oxidase in cornea and retina. Thus, an ACE oil ophthalmic formulation represent a promising therapy for ocular pathologies associated with arterial hypertension.

In vitro and in vivo evaluation of Δ9-tetrahidrocannabinol/PLGA nanoparticles for cancer chemotherapy.

Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells. In this work, a reproducible methodology is described to prepare Δ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles against lung cancer. The nanoformulation is further improved by surface functionalization with the biodegradable polymers chitosan and poly(ethylene glycol) (PEG) in order to optimize the biological fate and antitumor effect. Mean nanoparticle size (≈ 290 nm) increased upon coating with PEG, CS, and PEG-CS up to ≈ 590 nm, ≈ 745 nm, and ≈ 790 nm, respectively. Surface electrical charge was controlled by the type of polymeric coating onto the PLGA particles. Drug entrapment efficiencies (≈ 95%) were not affected by any of the polymeric coatings. On the opposite, the characteristic sustained (biphasic) Δ(9)-THC release from the particles can be accelerated or slowed down when using PEG or chitosan, respectively. Blood compatibility studies demonstrated the adequate in vivo safety margin of all of the PLGA-based nanoformulations, while protein adsorption investigations postulated the protective role of PEGylation against opsonization and plasma clearance. Cell viability studies comparing the activity of the nanoformulations against human A-549 and murine LL2 lung adenocarcinoma cells, and human embryo lung fibroblastic MRC-5 cells revealed a statistically significant selective cytotoxic effect toward the lung cancer cell lines. In addition, cytotoxicity assays in A-549 cells demonstrated the more intense anticancer activity of Δ(9)-THC-loaded PEGylated PLGA nanoparticles. These promising results were confirmed by in vivo studies in LL2 lung tumor-bearing immunocompetent C57BL/6 mice.

Drug targeting to cancer by nanoparticles surface functionalized with special biomolecules.

Nanoparticulate-based drug carriers have been developed to overcome the problems of conventional anticancer pharmacotherapy, i.e., the little specificity and low accumulation of the drug into the tumor interstitium, and the extensive biodistribution leading to severe toxicity. Unfortunately, conventional nanoparticles have been demonstrated to merely accumulate the loaded drug into organs associated to the reticuloendothelial system, e.g., the liver. Recently, drug delivery strategies involving the use of nanoplatforms surface decorated with unique biomolecules have demonstrated their potential in concentrating the chemotherapy agent specifically into the malignant cells. This review will be focused on the analysis of the current state of the art and future perspectives of such passive and active targeting strategies based on the enhanced permeability and retention effect and on a ligand-mediated transport, respectively. Special attention will be given to the use of these surface functionalized nanocarriers to overcome multi-drug resistances in cancer cells.

Nanostructures for drug delivery to the brain.

This review aims to summarize present approaches employed in delivering drugs to the central nervous system. Changes in blood-brain barrier (BBB) function have been reported in several neurological disorders. A brief description of the blood brain barrier and the main pathologies related to this barrier disfunction are described. Treatments for these disorders are based on several available strategies for delivering drugs into the brain, through circumvention of the BBB, as disruption of the BBB, prodrugs, molecular Trojan horses, among others. Particular attention will be placed on nanocarriers and more specifically on polymeric nanoparticles, which are presented as the most promising strategy for CNS delivery, helping drugs to be targeted more efficiently to the brain. This also allows attacking previously untreatable disorders such as brain tumors and other neurodegenerative diseases. New strategies and technologies commercialized by different pharmaceutical companies are also included.