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

Many different and innovative approaches have been investigated to reduce the barrier effects of the stratum corneum (SC) and one of those are microneedles. Microneedles (MNs) are micron-sized needles which assist drug delivery through skin by creating microchannels (micron-scale pores) in SC that are large enough to enable drugs, including macromolecules, to enter the skin while being small enough to avoid pain, irritation and needle phobia. They have the capacity to play a role in modern healthcare as they reduce pain, tissue damage and transmission of infection and have potential for selfadministration in comparison to traditional needles. MNs have been fabricated by a variety of methods, from a range of materials (including silicon, glass, metal, carbohydrates and polymers) and in varying geometries (Quinn et al., 2014). Additive manufacturing (AM), more commonly known as three-dimensional (3D) printing represents a new, cutting-edge technology of 3D objects fabricated from a digital model generated using computer-aided design (CAD) software by fusing or depositing proper material (e.g., ceramics, liquids, metal, plastic, powders or even living cells) in layers. Suitable thermoplastic material in the form of a filament is fed into the printer by rollers, where it is heated to just above its softening point (glass transition temperature, Tg) by heating elements into a molten state. The melted or softened material guided by gears is moved towards heat end where it is extruded from the printer’s head, through a nozzle and subsequently deposited layer-by-layer on a build plate, cooling and solidifying in under a second. The printer’s head moves within the xand y-axes, whereas the platform can move within the z-axis, thus creating 3D structures (Alhnan et al., 2016; Goole and Amighi, 2016; Jamróz, 2018; Prased and Smyth, 2016). The aim of this work was to fabricate biodegradable PLA microneedles using innovative FDM 3D-printing technology on two different 3D printers and then chemically etch their arrays to obtain ideally sized and shaped needles.

Approximately 70-90% of the new active pharmaceutical ingredients/drugs are poorly soluble in water/biological fluids. Improvement of solubility, dissolution rate, bioavailability are the main characteristics of drug nanocrystals that are important for oral drug administration. High bioadhesive activity, depending on the type of stabilizer, is considered to be an essential feature of drug nanocrystals for oral, dermal, ocular dosage forms (Chang et al., 2015; Sheokand et al., 2018; Tuomela et al., 2016). Drug nanocrystals are solid nanosized particles of pharmacologically active substances, mainly BCS class IIa and IIb, 200 to 600 nm in diameter, homogeneously coated with 10-50% stabilizer/surfactants and/or polymers, forming ultrafine dispersion (Malamatari et al., 2018). Drug nanocrystals are usually in the crystalline state, but depending on the manufacturing method and process parameters, they may be in the amorphous state (Shete et al., 2014). Drug nanocrystals can be obtained by increasing their particle size by controlled precipitation/agglomeration from solution or by reducing drug particle size by milling to the desirable size. The two basic methods for obtaining drug nanocrystals are bottom up (e.g., precipitation) and top down (e.g., milling) methods, or drug nanocrystals can be made by a combination of these processes. By combining these two methods the desired particle size of drugs can be achieved and disadvantages of the individual methods are overcomed. These methods are intended for the preparation of liquid pharmaceutical nanosuspensions whose internal phase consists of drug nanocrystals particles, which can be converted into solid drug nanocrystals by post-production processes (spray drying, freeze drying or other process) in order to improve chemical, physical stability of drug during storage, when the selected stabilizer of drug nanocrystal could not provide long-term stability of the liquid nanosuspension (Sheokand et al., 2018).

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.

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.

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.