MicroRNAs (miRNAs) represent endogenous small RNAs that post-transcriptionally regulate gene expression and, thus they are involved in the onset and progression of various diseases and conditions (Bader et al., 2010) such as for overweight and obesity. Antiadipogenic miRNA-27a is a negative regulator in fat metabolism, which inhibits adipocyte differentiation through downregulation of adipogenic marker genes (e.g. PPARγ) (Kim et al., 2010). Reduced miRNA-27a levels are often associated with the development of obesity and, therefore, this miRNA might represent a promising candidate for miRNA mimic replacement therapy (Lin et al., 2009). However, the application of naked RNAs has shown low membrane permeability, cellular uptake, and rapid degradation in the circulation. The present study aimed to develop a cationic, lipid-based nanoparticle system for targeting adipose tissue and delivering miRNA-27a. These systems are composed of positively charged nanostructured lipid carriers (cNLCs) and negatively charged miRNAs, which results in complex formation based on electrostatic interactions between these components. Materials and methods
Omeprazole is a proton pump inhibitor commonly used in pediatric patients (Wensel, 2009). Pediatric patients are usually unable to swallow solid dosage forms and they need dose adjustment. Therefore, the dosage form of choice for this population is compounded liquid preparation. Since pharmacies don't usually dispose of pure active substances, compounded liquid preparations are most commonly prepared from commercially available solid dosage forms, in a way that tablets are simply pulverized or capsule contents emptied, adding water or one of the commercially available vehicles (Haywood and Glass, 2013). Considering the risks associated with the preparation and use of compounded preparations, the Chapter <795> of the US Pharmacopoeia states that the beyond-use date is 14 days for non-preserved aqueous oral formulations, if stored in the refrigerator. Preserved aqueous preparations can be stored for 35 days at controlled room temperature or in the refrigerator (USP, 2015).
Although transdermal drug delivery systems (DDS) offer numerous benefits for patients, including the avoidance of both gastric irritation and first-pass metabolism effect, as well as improved patient compliance, only a limited number of active pharmaceutical ingredients (APIs) can be delivered accordingly. Microneedles (MNs) represent one of the most promising concepts for effective transdermal drug delivery that penetrate the protective skin barrier in a minimally invasive and painless manner. The first MNs were produced in the 90s, and since then, this field has been continually evolving. Therefore, different manufacturing methods, not only for MNs but also MN molds, are introduced, which allows for the cost-effective production of MNs for drug and vaccine delivery and even diagnostic/monitoring purposes. The focus of this review is to give a brief overview of MN characteristics, material composition, as well as the production and commercial development of MN-based systems.
Cationic NLCs represent lipid vesicles bearing cationic lipids on its surface, which leads to electrostatic interactions with negative charges of the nucleic acids such as miRNA and formation of a complex which protect the nucleic acids from the inevitable physicochemical biological impacts within the blood circulation [1]. This study aimed to develop cNLCs in order to obtain the most suitable formulation for further delivery of miRNAs.
Oil-in-water cationic nanoemulsions (CNE) are fine dispersions consisting of an oil core (from natural or synthetic origin) stabilized by a single cationic lipid or a mixture with phospholipids, non-ionic surfactants, and/or PEG-lipids. CNEs are considered to be suitable and potential delivery system for nucleic acids in gene therapy field due to their positively charged surface which complex with negatively charged gene material through electrostatic interactions [1]. The aim of the present study was to evaluate the effect of cationic lipid-sterylamine (SA) on mean droplet size, zeta potential and pH of the CNEs. Formulations containing various concentrations of SA were prepared on high-pressure homogenizer. The mean droplet size and zeta potential of the emulsions were determined by photon correlation spectroscopy and electrophoretic light scattering, respectively (Malvern NanoZs Zetasizer). The mean droplet size of emulsions varied from 126 to 129 nm while the polydispersity index varied from 0,068 to 0,137. As expected, zeta-potential increased from +43,7 mV to +53,7 mV with the SA concentration increase from 0,25 to 0,75 % (w/w). During the 60-day storage period at 25 °C, the droplets stayed in the nanometer range with only a minor size increase (~10 nm), no significant changes in droplet size distribution nor zeta potential or any difference in their visual appearance (no creaming or phase separation) proving therefore a satisfactory formulation stability.
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