Gold Nanoparticle-Quantum Dot Fluorescent Nanohybrid:Application for Localized Surface Plasmon Resonance-induced Molecular Beacon Ultrasensitive DNA Detection

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Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: an in-vivo study in rats and mice.

The efficacy of an antisense oligonucleotide (ODN17) cationic nanoemulsion directed at VEGF-R2 to reduce neovascularization was evaluated using rat corneal neovascularization and retinopathy of prematurity (ROP) mouse models. Application of saline solution or scrambled ODN17 solution on eyes of rats led to the highest extent of corneal neovascularization. The groups treated with blank nanoemulsion or scrambled ODN17 nanoemulsion showed moderate inhibition in corneal neovascularization with no significant difference with the saline and scrambled ODN17 control solution groups, while the groups treated with ODN17 solution or Avastin® (positive ODN17 control) clearly elicited marked significant inhibition in corneal neovascularization confirming the results reported in the literature. The highest significant corneal neovascularization inhibition efficiency was noted in the groups treated with ODN17 nanoemulsion (topical and subconjunctivally). However, in the ROP mouse model, the ODN17 in PBS induced a 34% inhibition of retinal neovascularization when compared to the aqueous-vehicle-injected eyes. A significantly higher inhibition of vitreal neovascularization (64%) was observed in the group of eyes treated with ODN17 nanoemulsion. No difference in extent of neovascularization was observed between blank nanoemulsion, scrambled ODN17 nanoemulsion, vehicle or non-treated eyes. The overall results indicate that cationic nanoemulsion can be considered a promising potential ocular delivery system and an effective therapeutic tool of high clinical significance in the prevention and forthcoming treatment of ocular neovascular diseases

The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.

Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions

Topical and intravitreous administration of cationic nanoemulsions to deliver antisense oligonucleotides directed towards VEGF KDR receptors to the eye.

Antisense oligonucleotides (ODNs) specific for VEGFR-2-(17 MER) and inhibiting HUVEC proliferation in-vitro were screened. One efficient sequence was selected and incorporated in different types of nanoemulsions the potential toxicity of which was evaluated on HUVEC and ARPE19 cells. Our results showed that below 10 microl/ml, a 2.5% mid-chain triglycerides cationic DOTAP nanoemulsion was non-toxic on HUVEC and retinal cells. This formulation was therefore chosen for further experiments. In-vitro transfection of FITC ODNs in ARPE cells using DOTAP nanoemulsions showed that nanodroplets do penetrate into the cells. Furthermore, ODNs are released from the nanoemulsion after 48 h and accumulate into the cell nuclei. In both ex-vivo and in-vivo ODN stability experiments in rabbit vitreous, it was noted that the nanoemulsion protected at least partially the ODN from degradation over 72 h. The kinetic results of fluorescent ODN (Hex) distribution in DOTAP nanoemulsion following intravitreal injection in the rat showed that the nanoemulsion penetrates all retinal cells. Pharmacokinetic and ocular tissue distribution of radioactive ODN following intravitreal injection in rabbits showed that the DOTAP nanoemulsion apparently enhanced the intraretinal penetration of the ODNs up to the inner nuclear layer (INL) and might yield potential therapeutic levels of ODN in the retina over 72 h post injection

Polymers in Ophthalmology

El articulo Polymers in ophthalmology es parte del capitulo 6 del libro Advanced polymers in medicine.Ophthalmological sciences are disciplines focused in the health of the eyes and related structures, as well as vision, visual systems, and vision information processing in humans; dealing with the anatomy, physiology and diseases of the eye. Along time a wide variety of materials, including metals, ceramics and polymers, have been developed and used in different ophthalmic applications. Although, modern ophthalmic devices and drug platforms are made with polymeric materials. Applications of polymers in ophthalmology include vitreous replacement fluids, contact lenses, intraocular lenses, artificial orbital walls, artificial corneas, artificial lacrimal ducts, glaucoma drainage devices, viscoelastic replacements, drug delivery systems, sclera buckles, retinal tacks and adhesives, and ocular endotamponades. Both synthetic and natural polymeric biomaterials are used in ophthalmological applications, although in the lasts years most efforts were focused in natural and biocompatible materials, such as gelatin, hyaluronan, chitosan, gums, etc.; developing, tablets, films, suspensions, nanosystems, inserts, etc. This chapter attempts to offers an insight into the importance of polymers in the design and development of pharmaceuticals platforms used in ocular therapeutics.Fil: Calles, Javier Adrián. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina.Fil: Bermudez, José María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química; Argentina.Fil: Bermudez, José María. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; Argentina.Fil: Valles, Enrique Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Bahía Blanca; Argentina.Fil: Valles, Enrique Marcelo. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Allemandi, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina.Fil: Allemandi, Daniel Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina.Fil: Palma, Santiago Daniel. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Otras Ciencias Química