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.
•Microparticles were decorated with two different molecular weights hyaluronic acid.•Hyaluronic acid corona discourage the diffusion of microparticles in the vitreous.•The molecular weight of the ...hyaluronic acid influence protein release kinetics.•Hyaluronic acid molecular weight influence the diffusion of the microparticles.•Hyaluronic acid molecular weight does not affect degradation time of microparticles.
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.
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-beta-cyclodextrin (HPbetaCD) 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 HPbetaCD.
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.
Microfluidic-based nanoscale drug delivery systems have risen to prominence in the field of precision nanomedicine in recent years. This intriguing innovation could provide unique therapeutic ...prospects in the treatment of serious disorders as traumatic brain injury, a potentially fatal condition that is widespread during childhood. According to current scientific study, neurotrophins are vital for the healing of injured brain parenchyma, and the brain-derived neurotrophic factor (BDNF) in particular may have significant regenerative effects. To address BDNF-related pharmacokinetic constraints, microfluidic-assisted manufacturing of BDNF-loaded solid lipid nanoparticles (BDNF-SLNs) was carried out, and following evaluation, the formulation demonstrated optimum characteristics in terms of size (190.3 ± 10.1 nm), PDI (0.180 ± 0.023), and ζ-potential (– 39.2 ± 1.30 mV). Short-term stability studies and the haemolysis assay verified the formulation's biocompatibility, while an in vitro permeability analysis revealed an increase in the Papp of the encapsulated BDNF (1.27x10−5 cm/s) as compared to plain BDNF (9.31x10−6 cm/s). The in vitro mimicked neuroinflammatory model demonstrated an enhanced decrease in nitrite production and Nos mRNA levels using BDNF-SLNs compared to plain BDNF as a control, validating the proficiency of the microfluidic-based drug delivery systems as pioneering and valuable approaches for the brain delivery of biologicals.
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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.
•Complexation of HC with all CDs was more effective in water than in a water:ethanol mixture.•HC-γCD and HC-βCD complexes exhibited a qualitatively different solubility profiles.•Solubility ...enhancement was the highest with HPβCD.•Potential implications for improving drug delivery systems in ocular inflammatory and autoimmune disorders.
Hydrocortisone (HC) is widely utilized in the pharmaceutical field for various administration routes, including oral, parenteral, and topical routes. However, its application in ocular disease treatment as a solution is limited due to its poor aqueous solubility. To address this limitation, in this study we aimed to investigate different types of cyclodextrins (CDs) to identify the most effective CD for improving the inherent solubility of HC. Results from scanning electron microscopy, rheology and differential scanning calorimetry (DSC) demonstrated the formation of inclusion complexes, while isothermal titration calorimetry (ITC) investigations accurately determined the thermodynamic parameters associated with the formation of complexes between HC and HPβCD or βCD, at 25 and 37 °C. Additionally, phase solubility studies in PBS buffer at 37 °C confirmed the formation of stable inclusion complexes. Collectively, results indicated that HPβCD was the most effective CD in enhancing the intrinsic solubility of HCs in PBS highlighting its potential for improving the solubility and formulation of HC-based pharmaceutical products.
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.
Additive manufacturing has the potential to create, repair, or enhance customized tools, but reliable processing guidelines for tool steels are necessary. This study focuses on printing H13 tool ...steel on a 316 L substrate using Laser-Directed Energy Deposition technology. A comprehensive study on the most influential process parameters was carried out, i.e. laser power (1400, 1600, 1800, 2000 W), powder feed rate (9, 12, 15 g/min) and scanning speed (1000, 1200 mm/min), for the production of single tracks. Cladding angle, aspect ratio, dilution, shift, microhardness, microstructures were selected as measured output. Manufacturing guidelines were established for a complete characterization of individual tracks, with a new approach for properly calculating the dilution. The tracks exhibited different properties and the influence of process parameters on the measured output was evaluated. The outcomes determine a technological window where it is possible to select the most sensible process parameters depending on the desired application.
Additive manufacturing is an advanced technology able to produce parts with different grades of complexity, including its shape, microstructure, functionality and material. Regarding material ...complexity nowadays, it is possible to produce polymer parts with customized reinforced fibre filling such as carbon, Kevlar or glass. However, their mechanical behaviour is still under investigation and no data are available on the bearing strength for additively manufactured composites. The aim of this work is to provide a contribution on this topic to ensure safe joint design with the current and innovative technologies. In this article the authors present the experimental characterization of polymer filled with Kevlar to pin bearing test. Samples have been designed as a function of filling and geometry parameters. Results have been analysed with statistical methods. Finding highlight similar and different behaviour regarding samples produced with conventional process. The most interesting result is that the authors demonstrate how the pin diameter is significant for the results, particularly for the stiffness keeping constant the bearing strength.
