Solid–lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in the body, combining low toxicity with a targeted delivery. Nanostructured lipid carriers are the second generation of lipid nanoparticles differing from solid lipid nanoparticles in their composition matrix. The use of a liquid lipid together with a solid lipid in nanostructured lipid carrier allows it to load a higher amount of drug, enhance drug release properties, and increase its stability. Therefore, a direct comparison between solid lipid nanoparticles and nanostructured lipid carriers is needed. This review aims to describe solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems, comparing both, while systematically elucidating their production methodologies, physicochemical characterization, and in vitro and in vivo performance. In addition, the toxicity concerns of these systems are focused on.

In the present study, we have demonstrated receptor for advanced glycation endproducts (RAGE) as a target for delivery of drugs specifically to triple negative breast cancer cells. We have prepared solid lipid nanoparticle formulation of cytotoxic agent di-allyl-disulfide (DADS) to overcome its bioavailability issues. Then, we have surface modified DADS-loaded solid lipid nanoparticles (DADS-SLN) with RAGE antibody to achieve site-specific delivery of DADS to TNBC cells. We found a significant cellular internalization of RAGE surface modified DADS-SLN (DADS-RAGE-SLN) when compared to DADS-SLN. The cytotoxic effect of DADS was also significantly improved with DADS-RAGE-SLN by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by western blot analysis. RAGE-targeted delivery of cytotoxic agents can be, therefore, a promising approach for improving antitumour activity and reducing off-target effects.

In the present study, solid lipid nanoparticles (SLNs) have been formulated as a carrier system for effective intracellular delivery of STAT3 inhibitor, niclosamide (Niclo) to triple negative breast cancer (TNBC) cells. Emulsification-solvent evaporation method was employed in formulation of Niclo loaded SLNs (Niclo-SLNs). The formula of Niclo-SLN was optimized by Box-Behnken design and characterized for their shape, size and surface charge. The in vitro anti-cancer efficacy of Niclo-SLNs was studied in TNBC cells. The prepared Niclo-SLNs were found to be spherical with the particle size of 112.18± 1.73 nm and zetapotential of 23.8±2.7mV. In the in vitro anticancer study the Niclo SLNs show a better cytotoxicity than the naïve Niclo, which is attributed to improved cell uptake of SLN formulation. In conclusion, the results of the present study demonstrate that the formulation of Niclo as SLNs will improve the anticancer efficacy against TNBC.

Optimization is a critical process in the development of nanoparticles to apprehend the formulation variables and quality attributes. The purpose of this study was to evaluate the influence of formulation variables viz., drug/polymer ratio (A), surfactant concentration (B) and ratio of volume of internal to external phase (C) on the dependent variables (particle size, % EE and zeta potential) of paclitaxel loaded poly (ε-caprolactone) nanoparticles using Box-Behnken design. The nanoparticles were fabricated using emulsion-solvent evaporation technique. The generated polynomial equations, contour plots and response surface plots of the design space were used to analyze the relationship between independent variables and the observed response. An optimal batch was formulated with selected variables (A: +1 level, B: 0 level, C: â1 level) and the prepared nanoparticles were found to have particle size 215.6 µm, zeta potential â7.52 mV and % drug entrapment 86.78%. The observed responses are in close agreement with the predicted values. NPs were spherical with a smooth surface as revealed by morphological studies and the drug-polymer compatibility was established using FTIR and thermal analysis. The drug was released from the NPs in a biphasic pattern with an initial burst release (32.1 %) followed by sustained release (53 %) at the end of 5 d. The in vitro cell cytotoxicity studies on MCF-7 cells showed that the NPs held superior tumor inhibition ability. The results encourage the application of Box-Behnken design for the optimization of critical variables and fabrication of nanoparticles with desirable properties for drug delivery. Keywords: Nanoparticles, Poly (ε-caprolactone), Box-Behnken design, Optimization, Characterizatio