In pharmaceutical technology, lipids and polymers are considered pillar excipients for the fabrication of most dosage forms, irrespective of the administration route. They play various roles ranging from support vehicles to release rate modifiers, stabilizers, solubilizers, permeation enhancers and transfection agents. Focusing on selected applications, which were discussed at the Annual Scientific Meeting of the Gattefossé Foundation 2018, this manuscript recapitulates the fundamental roles of these two important classes of excipients, either employed alone or in combination, and provides insight on their functional properties in various types of drug formulations. Emphasis is placed on oral formulations for the administration of active pharmaceutical ingredients with low aqueous solubilities or poor permeation properties. Additionally, this review article covers the use of lipids and polymers in the design of colloidal injectable delivery systems, and as substrates in additive manufacturing technologies for the production of tailor-made dosage forms.

Background: Nowadays, the downregulation of genes involved in the pathogenesis of severe lung diseases through local siRNA delivery appears an interesting therapeutic approach. In this study, we propose novel hybrid lipid-polymer nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. Methods: A panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully characterized. A combination of model siRNAs against the sodium transepithelial channel (ENaC) was entrapped in optimized hNPs comprising or not poly(ethylenimine) (PEI) as third component. siRNA-loaded hNPs were characterized for encapsulation efficiency, release kinetics, aerodynamic properties, and stability in artificial mucus (AM). The fate and cytotoxicity of hNPs upon aerosolization on a triple cell co-culture model (TCCC) mimicking human epithelial airway barrier were assessed. Finally, the effect of siRNA-loaded hNPs on ENaC protein expression at 72 hours was evaluated in A549 cells. Results: Optimized muco-inert hNPs encapsulating model siRNA with high efficiency were produced. The developed hNPs displayed a hydrodynamic diameter of ∼150 nm, a low polydispersity index, a negative ζ potential close to −25 mV, and a peculiar triphasic siRNA release lasting for 5 days, which slowed down in the presence of PEI. siRNA formulations showed optimal in vitro aerosol performance after delivery with a vibrating mesh nebulizer. Furthermore, small-angle X-ray scattering analyses highlighted an excellent stability upon incubation with AM, confirming the potential of hNPs for direct aerosolization on mucus-lined airways. Studies in TCCC confirmed that fluorescent hNPs are internalized inside airway epithelial cells and do not exert any cytotoxic or acute proinflammatory effect. Finally, a prolonged inhibition of ENaC protein expression was observed in A549 cells upon treatment with siRNA-loaded hNPs. Conclusions: Results demonstrate the great potential of hNPs as carriers for pulmonary delivery of siRNA, prompting toward investigation of their therapeutic effectiveness in severe lung diseases.

β-Sitosterol (β-Sit) is a dietary phytosterol with demonstrated anticancer activity against a panel of cancers, but its poor solubility in water limits its bioavailability and therapeutic efficacy. In this study, poly(lactide-co-glycolic acid) (PLGA) and block copolymers of poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) were used to encapsulate β-Sit into nanoparticles with the aim of enhancing its in vitro anticancer activity. β-Sitosterol-loaded PLGA and PEG-PLA nanoparticles (β-Sit-PLGA and β-Sit-PEG-PLA) were prepared by using a simple emulsion-solvent evaporation technique. The nanoparticles were characterized for size, particle size distribution, surface charge, and encapsulation efficiency. Their cellular uptake and antiproliferative activity was evaluated against MCF-7 and MDA-MB-231 human breast cancer cells using flow cytometry and MTT assays, respectively. β-Sit-PLGA and β-Sit-PEG-PLA nanoparticles were spherical in shape with average particle sizes of 215.0 ± 29.7 and 240.6 ± 23.3 nm, a zeta potential of −13.8 ± 1.61 and −23.5 ± 0.27 mV, respectively, and with narrow size distribution. The encapsulation efficiency of β-Sit was 62.89 ± 4.66 and 51.83 ± 19.72 % in PLGA and PEG-PLA nanoparticles, respectively. In vitro release in phosphate-buffered saline (PBS) and PBS/with 0.2% Tween 20 showed an initial burst release, followed by a sustained release for 408 h. β-Sit-PLGA nanoparticles were generally stable in a protein-rich medium, whereas β-Sit-PEG-PLA nanoparticles showed a tendency to aggregate. Flow cytometry analysis (FACS) indicated that β-Sit-PLGA nanoparticles were efficiently taken up by the cells in contrast to β-Sit-PEG-PLA nanoparticles. β-Sit-PLGA nanoparticles were therefore selected to evaluate antiproliferative activity. Cell viability was inhibited by up to 80% in a concentration range of 6.64–53.08 μg/mL compared to the untreated cells. Taken together, encapsulation of β-Sitosterol in PLGA nanoparticles is a promising strategy to enhance its anticancer activity against breast cancer cells.