Cyril J.F. Kahn

Liposome encapsulation of curcumin: Physico-chemical characterizations and effects on MCF7 cancer cell proliferation

The role of curcumin (diferuloylmethane), for cancer treatment has been an area of growing interest. However, due to its low absorption, the poor bioavailability of curcumin limits its clinical use. In this study, we reported an approach of encapsulation a curcumin by nanoliposome to achieve an improved bioavailability of a poorly absorbed hydrophobic compound. We demonstrated that liposomal preparations to deliver curcumin increase its bioavailability. Liposomes composed of salmons lecithin also improved curcumin bioavailability compared to those constituted of rapeseed and soya lecithins. A real-time label-free cell analysis system based on real-time cell impedance monitoring was used to investigate the in vitro cytotoxicity of liposomal preparations.

A Poly(lactic-co-glycolic acid) Knitted Scaffold for Tendon Tissue Engineering: An In Vitro and In Vivo Study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

Elaboration and characterization of nanoliposome made of soya; rapeseed and salmon lecithins: application to cell culture.

Health benefits of unsaturated fatty acids have been demonstrated over the last decades. Nanotechnology provided new process to produce particles such as liposomes and nanoliposomes made of pure phospholipids. These techniques are already used in pharmaceutics to augment the bioavailability and the bioefficiency of drugs. The aim of this paper is to characterize and evaluate the potential of nanoliposomes made of three lecithins (soya, rapeseed and salmon) on cell culture in order to use them in the future as drug delivery systems for tissue engineering. We began to measure, with zetasizer, the radius size of liposomes particles which are 125.5, 136.7 and 130.3 nm respectively for rapeseed, soya and salmon lecithin. Simultaneously, solutions observed by TEM demonstrated the particles were made much of liposomes than droplet (emulsion). Finally, we found that the solutions of lecithins were enough stable over 5 days at 37 °C to be used in culture medium. We investigated the effect of soya, rapeseed and salmon lecithin liposome from 2mg/mL to 5.2 μg/mL on metabolic activity and cell proliferation on rat bone marrow stem cells (rBMSC) during 14 days. The results showed that the three lecithins (soya, rapeseed and salmon) improve cell proliferation at different concentration.

Chitosan-coated liposomes encapsulating curcumin: study of lipid–polysaccharide interactions and nanovesicle behavior

Despite various spectacular therapeutic properties, curcumin has low bioavailability mainly due to its poor solubility in water. In this paper, we encapsulated curcumin by nanoliposomes prepared from salmon purified phospholipid and coated with chitosan. Various techniques were used in order to study the interactions among phospholipid, chitosan and curcumin. FTIR results showed both electrostatic and hydrophobic interactions as well as hydrogen bonding between chitosan and phospholipid, while hydrophobic forces and hydrogen bonding dominated the interactions between curcumin and phospholipid as well as between curcumin and chitosan. Shear viscosity measurements demonstrated a flow behavior change from Newtonian to shear thinning after liposome coating. The increase/decrease stress ramp showed that the addition of chitosan layer decreased significantly the hysteresis loop area (thixotropic behavior) and therefore increased significantly the liposomal dispersion stability. The viscoelastic properties investigated by small-amplitude oscillatory shear rheology demonstrated improvement of mechanical stability after chitosan addition. Small-angle X-ray scattering experiments revealed that the liposome membrane structure was not affected by the chitosan layer or the encapsulated curcumin.

Effects of Ar―H2―N2 microwave plasma on chitosan and its nanoliposomes blend thin films designed for tissue engineering applications

This work addresses the functionalization of chitosan thin films and its nanoliposomes blend films by a microwave-excited Ar/N2/H2 surface-wave plasma treatment which was found an effective tool to modify surface properties. Changes in the film properties (wettability, chemical composition, morphology) induced by the plasma treatment are studied using water contact angle measurements, X-ray photoelectron spectroscopy and scanning probe microscopy. The results suggest that hydrophilicity of the films is improved by plasma treatment in a plasma condition dependency manner. Water contact angle of chitosan films before and after plasma treatment are, respectively, 101° and 27°. Besides chemical changes on the surface, the nanoliposomes incorporation and plasma treatment also induce morphological modifications. Moreover, a correlation is found between the nanoliposomes composition and size, and the effects of plasma treatment. It is shown that the plasma treatment significantly improves the chitosan film functionalization. The effect of N2 content (88% and 100%) in the plasma gas mixture on the film etching is also pointed out.

Natural lecithin promotes neural network complexity and activity

Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called “essential” fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications.

Synthesis and Characterization of Nanofunctionalized Gelatin Methacrylate Hydrogels

Given the importance of the extracellular medium during tissue formation, it was wise to develop an artificial structure that mimics the extracellular matrix while having improved physico-chemical properties. That is why the choice was focused on gelatin methacryloyl (GelMA), an inexpensive biocompatible hydrogel. Physicochemical and mechanical properties were improved by the incorporation of nanoparticles developed from two innovative fabrication processes: High shear fluid and low frequencies/high frequencies ultrasounds. Both rapeseed nanoliposomes and nanodroplets were successfully incorporated in the GelMA networks during the photo polymerization process. The impact on polymer microstructure was investigated by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and enzymatic degradation investigations. Mechanical stability and viscoelastic tests were conducted to demonstrate the beneficial effect of the functionalization on GelMA hydrogels. Adding nanoparticles to GelMA improved the surface properties (porosity), tuned swelling, and degradability properties. In addition, we observed that nanoemulsion didn’t change significantly the mechanical properties to shear and compression solicitations, whereas nanoliposome addition decreased Young’s modulus under compression solicitations. Thus, these ways of functionalization allow controlling the design of the material by choosing the type of nanoparticle (nanoliposome or nanoemulsion) in function of the application.

Application of a thermodynamic model to mechanical properties of rabbit Achilles tendon

Ligaments and tendons play an essential role in stability and motion in the musculoskeletal systemwith a complex multiple scale hierarchical structure of collagen fibres difficult to wellmodel. In tissueengineeringevaluationofnative tissues, scaffolds, and regenerated tissue is an important issue. To our knowledge, mechanical evaluation in tissue engineering is limited to relative simple solicitation of uniaxial strain with or without relaxation. Our studies on mechanical properties of ligament and tendon show that those tests are insufficient to well characterise them. The aim of the present work was therefore to develop a model which can describe complex uniaxial strain history such as loading, unloading reloading cycles.

Bioactive Films Containing Alginate-Pectin Composite Microbeads with Lactococcus lactis subsp. lactis: Physicochemical Characterization and Antilisterial Activity

Novel bioactive films were developed from the incorporation of Lactococcus lactis into polysaccharide films. Two different biopolymers were tested: cellulose derivative (hydroxylpropylmethylcellulose (HPMC)) and corn starch. Lactic acid bacteria (LAB) free or previously encapsulated in alginate-pectin composite hydrogel microbeads were added directly to the film forming solution and films were obtained by casting. In order to study the impact of the incorporation of the protective culture into the biopolymer matrix, the water vapour permeability, oxygen permeability, optical and mechanical properties of the dry films were evaluated. Furthermore, the antimicrobial effect of bioactive films against Listeria monocytogenes was studied in synthetic medium. Results showed that the addition of LAB or alginate-pectin microbeads modified slightly films optical properties. In comparison with HPMC films, starch matrix proves to be more sensitive to the addition of bacterial cells or beads. Indeed, mechanical resistance of corn starch films was lower but barrier properties were improved, certainly related to the possible establishment of interactions between alginate-pectin beads and starch. HPMC and starch films containing encapsulated bioactive culture showed a complete inhibition of listerial growth during the first five days of storage at 5 °C and a reduction of 5 logs after 12 days.

Mechanical properties evolution of a PLGA-PLCL composite scaffold for ligament tissue engineering under static and cyclic traction-torsion in vitro culture conditions

This study aims to investigate the in vitro degradation of a poly(L-lactic-co-glycolic acid)-poly(L-lactic-co-ϵ-caprolactone) (PLGA-PLCL) composite scaffold’s mechanical properties under static culture condition and 2 h period per day of traction-torsion cyclic culture conditions of simultaneous 10% uniaxial strain and 90° of torsion cycles at 0.33 Hz. Scaffolds were cultured in static conditions, during 28 days, with or without cell seeded or under dynamic conditions during 14 days in a bioreactor. Scaffolds’ biocompatibility and proliferation were investigated with Alamar Blue tests and cell nuclei staining. Scaffolds’ mechanical properties were tested during degradation by uniaxial traction test. The PLGA-PLCL composite scaffold showed a good cytocompatibility and a high degree of colonization in static conditions. Mechanical tests showed a competition between two process of degradation which have been associated to hydrolytic and enzymatic degradation for the reinforce yarn in poly(L-lactic-co-glycolic acid) (PLGA). The enzymatic degradation led to a decrease effect on mechanical properties of cell-seeded scaffolds during the 21st days, but the hydrolytic degradation was preponderant at day 28. In conclusion, the structure of this scaffold is adapted to culture in terms of biocompatibility and cell orientation (microfiber) but must be improved by delaying the degradation of it reinforce structure in PLGA.