Unravelling the role of lipid composition on liposome-protein interactions.

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.

In Vitro and In Vivo Safety of Hyaluronic Acid-Decorated Microparticles for Intravitreal Injection of Palmitoylethanolamide, Citicoline, or Glial-Cell-Derived Neurotrophic Factor.

The treatment of posterior eye segment diseases through intravitreal injection requires repeated injections of an active molecule, which may be associated with serious side effects and poor patient compliance. One brilliant strategy to overcome these issues is the use of drug-loaded microparticles for sustained release, aiming at reducing the frequency of injections. Therefore, the aim of this work was to assess the safety features of poly(lactic-co-glycolic acid) (PLGA)-based, hyaluronic acid-decorated microparticles loaded with palmitoylethanolamide (PEA), citicoline (CIT), or glial-cell-derived neurotrophic factor (GDNF). Microparticles were prepared by double emulsion-solvent evaporation and fully characterized for their technological features. Microparticles possessed a satisfactory safety profile in vitro on human retinal pigment epithelial (ARPE-19) cells. Interestingly, the administration of free GDNF led to a loss of cell viability, while GDNF sustained release displayed a positive effect in that regard. In vivo results confirmed the safety profile of both empty and loaded microparticles. Overall, the outcomes suggest that the produced microparticles are promising for improving the local administration of neuroprotective molecules. Further studies will be devoted to assess the therapeutic ability of microparticles.

Investigating the Effect of Surface Hydrophilicity on the Destiny of PLGA-Poloxamer Nanoparticles in an In Vivo Animal Model.

This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.

Physico-Chemical Properties and Valorization of Biopolymers Derived from Food Processing Waste.

The widespread use of synthetic plastics, as well as the waste produced at the end of their life cycle, poses serious environmental issues. In this context, bio-based plastics, i.e., natural polymers produced from renewable resources, represent a promising alternative to petroleum-based materials. One potential source of biopolymers is waste from the food industry, the use of which also provides a sustainable and eco-friendly solution to waste management. Thus, the aim of this work concerns the extraction of polysaccharide fractions from lemon, tomato and fennel waste. Characterizing the chemical-physical and thermodynamic properties of these polysaccharides is an essential step in evaluating their potential applications. Hence, the solubility of the extracted polysaccharides in different solvents, including water and organic solvents, was determined since it is an important parameter that determines their properties and applications. Also, acid-base titration was carried out, along with thermoanalytical tests through differential scanning calorimetry. Finally, the electrospinning of waste polysaccharides was investigated to explore the feasibility of obtaining polysaccharide-based membranes. Indeed, electrospun fibers are a promising structure/system via which it is possible to apply waste polysaccharides in packaging or well-being applications. Thanks to processing feasibility, it is possible to electrospin waste polysaccharides by combining them with different materials to obtain porous 3D membranes made of nanosized fibers.

Characterization of Hyaluronic Acid-Coated PLGA Nanoparticles by Surface-Enhanced Raman Spectroscopy.

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.

Skin permeation and thermodynamic features of curcumin-loaded liposomes.

This work describes the development of liposomes encapsulating curcumin (CURC) aiming to provide insights on the influence of CURC on the thermodynamic and skin permeation/penetration features of the vesicles. CURC-loaded liposomes were prepared by hydration of lipid film, in the 0.1-15% CURC:DPPC w/w ratio range. The obtained formulations were characterized for their size distribution, zeta potential and vesicle deformability, along with their thermodynamic properties and ex vivo skin penetration/permeation ability. Liposome size was 110-130 nm for all formulations, with fairly narrow size distribution (polydispersity index was ≤0.20) and a zeta potential mildly decreasing with CURC loading. DSC outcomes indicated that CURC interferes with the packing of DPPC acyl chains in liposome bilayer when CURC percentage was at least 10%, leading to a more fluid state than blank and low-payload vesicles. Consistently, the deformability index of liposomes with 15% CURC:DPPC was strongly increased compared to other formulations. This is congruent with ex vivo skin penetration/permeation results, which showed how more deformable liposomes showed an improved deposition in the epidermis, which acts as a reservoir for the active molecule. Altogether, results hint at a possible application of high payload liposomes for improved topical dermal accumulations of actives.

Innovative Pharmaceutical Techniques for Paediatric Dosage Forms: A Systematic Review on 3D Printing, Prilling/Vibration and Microfluidic Platform.

The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure therapeutic efficacy, safety, and tolerability in paediatric patients, who have specific physiological needs and characteristics. In recent years, there has been a significant increase in attention towards this area, driven by the need to improve drug administration to children and ensure optimal and specific treatments. Technological innovation has played a crucial role in meeting these requirements, opening new frontiers in the design and production of paediatric pharmaceutical forms. In particular, three emerging technologies have garnered considerable interest and attention within the scientific and industrial community: 3D printing, prilling/vibration, and microfluidics. These technologies offer advanced approaches for the design, production, and customization of paediatric pharmaceutical forms, allowing for more precise dosage modulation, improved solubility, and greater drug acceptability. In this review, we delve into these cutting-edge technologies and their impact on the production of paediatric pharmaceutical forms. We analyse their potential, associated challenges, and recent developments, providing a comprehensive overview of the opportunities that these innovative methodologies offer to the pharmaceutical sector. We examine different pharmaceutical forms generated using these techniques, evaluating their advantages and disadvantages.

Thermosensitive In Situ Gelling Poloxamers/Hyaluronic Acid Gels for Hydrocortisone Ocular Delivery.

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye's surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel-water interactions, indicating that HA affects the water-polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

Hyaluronan-coated nanoparticles for active tumor targeting: Influence of polysaccharide molecular weight on cell uptake.

Here we aimed to correlate different molecular weights of hyaluronic acid (HA), 200, 800 and 1437 kDa, used to decorate poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs), to their cell uptakes. NP internalization kinetics in CD44-overexpressing breast carcinoma cells were quantified, using healthy fibroblast cells as reference. Actually, NP uptake and selectivity by tumor cells were maximized for NPs HA 800 kDa, while being minimum for NPs HA1400 kDa. This unexpected result could be explained considering that the interaction between NPs and tumor cells is dictated by rearrangement and conformation of that segment of HA chain that actually protrudes from the NPs. Overall, results obtained in this work point at how HA molecular weight, is pivotal project parameter in NP formulation to promote active targeting in the CD44 overexpressing cancer cells.

Drug micro-carriers with a hyaluronic acid corona toward a diffusion-limited aggregation within the vitreous body.

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.