Improved synthesis and characterization of cholesteryl oleate-loaded cationic solid lipid nanoparticles with high transfection efficiency for gene therapy applications.

The development of new nanoparticle formulations that are capable of high transfection efficiency without toxicity is essential to provide new tools for gene therapy. However, the issues of complex, poorly reproducible manufacturing methods, and low efficiencies during in vivo testing have prevented translation to the clinic. We have previously reported the use of cholesteryl oleate as a novel excipient for solid lipid nanoparticles (SLNs) for the development of highly efficient and nontoxic nucleic acid delivery carriers.

Topical Administration of Bosentan Prevents Retinal Neurodegeneration in Experimental Diabetes.

Experimental evidence suggests that endothelin 1 (ET-1) is involved in the development of retinal microvascular abnormalities induced by diabetes. The effects of ET-1 are mediated by endothelin A- and B-receptors (ETA and ETB). Endothelin B-receptors activation mediates retinal neurodegeneration but there are no data regarding the effectiveness of ETB receptor blockage in arresting retinal neurodegeneration induced by diabetes.

Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy.

Background: Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs.

Aim: The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN-nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake.

Improved formulation of cationic solid lipid nanoparticles displays cellular uptake and biological activity of nucleic acids.

Non-viral delivery using cationic solid lipid nanoparticles (SLNs) represents a useful strategy to introduce large DNA and RNA molecules to target cells. A careful selection of components and their amounts is critical to improve transfection efficiency. In this work, a selected and optimized formulation of SLNs was used to efficiently transfect circular DNA and linear RNA molecules into cells.

Approach to design space from retrospective quality data.

Context: Nowadays, the entire manufacturing process is based on the current GMPs, which emphasize the reproducibility of the process, and companies have a lot of recorded data about their processes.

Objective: The establishment of the design space (DS) from retrospective data for a wet compression process.

Materials And Methods: A design of experiments (DoE) with historical data from 4 years of industrial production has been carried out using the experimental factors as the results of the previous risk analysis and eight key parameters (quality specifications) that encompassed process and quality control data.

Chitosan nanoparticles as non-viral gene delivery systems: determination of loading efficiency.

Chitosan has been studied for use in particle delivery systems for therapeutic purposes, since one of its most important applications is as a non-viral vector in gene therapy. Due to its positive charge, it is capable of forming DNA complexes (polyplexes) obtained through several methods and with the property of protecting nucleic acids. Two methods for obtaining the nanoparticles of chitosan-nucleic acids are reported in this study: simple complexation (of depolymerized chitosan or of different chitosan salts with plasmid) and ionic gelation (by adsorption of plasmid in the nanoparticles or by encapsulation of plasmid into nanoparticles).

A new optimized formulation of cationic solid lipid nanoparticles intended for gene delivery: development, characterization and DNA binding efficiency of TCERG1 expression plasmid.

Solid lipid nanoparticles (SLNs) are being considered as a new approach for therapeutics for many known diseases. In addition to drug delivery, their use as non-viral vectors for gene delivery can be achieved by the inclusion of cationic lipids, which provide a positive surface potential that favours binding to the DNA backbone. This work is based on the idea that the optimization of the components is required as the first step in simplifying the qualitative and quantitative composition of SLNs as much as possible without affecting the essential properties that define SLNs as optimal non-viral vectors for gene delivery.

Quality and integrity of data in research, development, and innovation: a risk analysis method applied to laboratory notebooks in a university pilot plant.

Unlabelled: Risk analysis tools can be applied in the early stages of the research, development, and innovation of pharmaceutical drugs. We used a risk ranking and filtering method to optimize time resources in internal audits of project development documents in order to ensure traceability in a university pilot plant. Data gathered during audits undertaken over a 14 month period were classified according to risk factors at several levels.

Application of a validated method in the stability study of colistin sulfate and methylparaben in a veterinary suspension formulation by high-performance liquid chromatography with a diode array detector.

A methodology following International Cooperation on Harmonization for Veterinary Products (VICH) guidelines for the stability evaluation of colistin sulfate in a nonaqueous suspension pharmaceutical dosage form for veterinary use (via their drinking water) is described. This method monitors the percentage of colistin sulfate during the stability study of the preparation in drinking water and establishes the shelf life of the final product by a new high-performance liquid chromatography method which was developed and validated for the simultaneous determination of colistin sulfate [colistin A (Polymixin E1) and colistin B (Polymixin E2)] and methylparaben (Nipagin) using a diode array detector (DAD). The method uses a Kromasil C18 column and isocratic elution.