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Upon in vivo administration of nanoparticles, a protein corona forms on their surface and affects their half-life in circulation, biodistribution properties, and stability; in turn, the composition of the protein corona depends on the physico-chemical properties of the nanoparticles. We have previously observed lipid composition-dependent in vitro and in vivo microRNA delivery from lipid nanoparticles. Here, we carried out an extensive physico-chemical characterisation to understand the role of the lipid composition on the in vivo fate of lipid-based nanoparticles. We used a combination of differential scanning calorimetry (DSC), membrane deformability measurements, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS) to probe the interactions between the nanoparticle surface and bovine serum albumin (BSA) as a model protein. The lipid composition influenced membrane deformability, improved lipid intermixing, and affected the formation of lipid domains while BSA binding to the liposome surface was affected by the PEGylated lipid content and the presence of cholesterol. These findings highlight the importance of the lipid composition on the protein-liposome interaction and provide important insights for the design of lipid-based nanoparticles for drug delivery applications.

Nanoparticles (NPs) coated with hyaluronic acid (HA) seem to be increasingly promising for targeted therapy due to HA chemical versatility, which allows them to bind drugs of different natures, and their affinity with the transmembrane receptor CD-44, overexpressed in tumor cells. However, an essential aspect for clinical use of NPs is formulation stability over time. For these reasons, analytical techniques capable of characterizing their physico-chemical properties are needed. In this work, poly(lactide-co-glycolide) (PLGA) NPs with an average diameter of 100–150 nm, coated with a few 10 s of nm of HA, were synthesized. For stability characterization, two complementary investigative techniques were used: Dynamic Light Scattering (DLS) and Surface-Enhanced Raman Scattering (SERS) spectroscopy. The first technique provided information on size, polidispersity index, and zeta-potential, and the second provided a deeper insight on the NP surface chemicals, allowing distinguishing of HA-coated NPs from uncoated ones. Furthermore, in order to estimate formulation stability over time, NPs were measured and monitored for two weeks. SERS results showed a progressive decrease in the signal associated with HA, which, however, is not detectable by the DLS measurements.

Curcumin (CURC) is endowed with many pharmacological properties, among these anti-inflammatory, antioxidant, antimicrobial, and anticancer activity. Unfortunately, CURC is basically water-insoluble and undergoes a rapid photodegradation, chemical degradation, and metabolism. CURC stability and solubility can be improved by the complexation with cyclodextrins, which are cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic cavity. Thus, in this work, the formation of the inclusion complex between the semisynthetic hydroxypropyl-β-cyclodextrin (HPβCD) and CURC has been studied by means of phase solubility, differential scanning calorimetry and isothermal calorimetry experiments to assess the formation, stoichiometry and affinity constant of the obtained inclusion complexes. The thermodynamics of the complex formation has been studied in different hydroalcoholic solutions and the experiments have been performed at physiological and acidic pH to verify the effect of the ionization state on the efficacy of complex formation. Results show the relevance in the choice of the pH, solvent, and mixing time on the formation of the inclusion complex between active drug(s) and HPβCD.

Posterior eye segment diseases are treated through monthly intravitreal injections, that evoke serious side effects. A promising approach to reduce injection frequency consists in producing biodegradable microspheres (MPs) releasing the protein in the vitreous body for long times. Moreover, a rational design of these MPs requires a discouraged diffusion/sedimentation within the intravitreal space, which are detrimental for the vision and the control over drug release kinetics. In this work, poly(lactic-co-glycolic acid) (PLGA)-based MPs encapsulating bovine serum albumin (BSA) were coated with hyaluronic acid (HA) at two molecular weights and tested for their release, diffusion and degradation features in simulated vitreous body (SVB). Results indicate that HA corona prolongs MP degradation time and BSA release. Furthermore, HA coating increased the affinity between MPs and SVB, thereby repressing device transport compared to control PLGA MPs. Results hold promise for the possible application of HA-decorated MPs for intravitreal injection of protein drugs.