MicroRNA-based medicines have drawn attention as a promising tool for the treatment of various diseases. Due to the poor biomembrane permeation, cellular uptake, and enzymatic instability of naked microRNA, the clinical success of gene therapy is mostly dependent on formulating efficient and safe transfection vectors [1]. Therefore, we aimed to develop cationic solid lipid nanoparticles (SLN) for gene therapy purposes. SLN containing 0.15% of stearylamine, 4.85% of Precirol ATO 5 (solid lipid), 1% of Tween 80, and 1% of Poloxamer 188, as non-ionic surfactants, were produced using a high-pressure homogenization process (800 bar and three cycles). microRNA 27-a was further complexed with SLN in the following SLN/microRNA ratios: 1:5, 1:2.5, 1:1, 2.5:1, 5:1, 10:1, 25:1 and characterized using dynamic light scattering, electrophoretic light scattering, and gel retardation assay. The SLN had a mean diameter of 112 ± 0.5 nm (PDI of 0.202 ± 0.011) and a zeta potential (ZP) value of +30.6 ± 1.25 mV. Complexation of SLNs with microRNA decreased a particle size from 244.8 ± 2.7 to 120.4 ± 0.4 nm with an increasing weight ratio of SLNs, while the biggest particle size was observed in 1:1 ratio (1146 ± 110.2 nm) due to low ZP values (3.45 ± 0.2 mV). Further, ZP increased from -14.3 ± 0.4 mV to + 39.7 ± 0.5 mV. Both ELS data and gel retardation assay results revealed that complete complexation could be attained above the weight ratio of 5:1. Our investigations suggest that SLN poses a high potential to be non-viral gene carriers in miRNA replacement therapy.

......................................................................................................................... 6 Introduction .................................................................................................................... 7 Theory ............................................................................................................................ 9 Computational Details and Methodology .......................................................................... 13 Results and Discussion Gibbs Reaction Energies ...................................................................................... 16 Dipoles and First Hyperpolarizabilities ................................................................... 22 Gibbs Activation Energies and Thermal Half-Lives ................................................. 25 Wiberg Indices .................................................................................................... 29 Conclusions .................................................................................................................. 33 References .................................................................................................................... 34

In this paper, the tradeoff between spectrum efficiency (SE) and energy efficiency (EE) is investigated in terms of interference management and power allocation for heterogeneous networks (HetNets) with non-orthogonal multiple access (NOMA). The EE and SE tradeoff is modeled as a multi-objective problem (MOP) under the maximum power and quality of service (QoS) constraints, which is non-convex. The MOP is relaxed into a convex single objective problem (SOP) by adopting a weighted sum strategy with the hypograph transformation. The SOP is solved in two steps. In the first step, we propose a power allocation technique based on non-cooperative (NC) game for EE and SE in NOMA HetNets. In the proposed NC game, the macro base station (MBS) and the small BSs (SBSs) compete with an equal priority in order to optimize their transmit powers towards maximizing the weighted sum of SE and EE. In the second step, a closed-form formula is proposed to control the power allocated to users taking into account both QoS constraint and successive interference cancellation (SIC) condition. From simulations, the proposed technique can, in some dedicated settings, considerably improve the tradeoff between EE and SE over conventional techniques.