Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.
We have developed a reproducible and facile one step strategy for the synthesis of doxorubicin loaded magnetoliposomes by using a thin-layer evaporation method. Liposomes of around 200 nm were made of 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and iron oxide nanoparticles (NP) with negative, positive and hydrophobic surfaces that were incorporated outside, inside or between the lipid bilayers, respectively. To characterize how NP are incorporated in liposomes, advanced cryoTEM and atomic force microscope (AFM) techniques have been used. It was observed that only when the NP are attached outside the liposomes, the membrane integrity is preserved (lipid melt transition shifts to 38.7 ºC with high enthalpy 34.8 J/g) avoiding the leakage of encapsulated drug while having good colloidal properties and the best heating efficiency under an alternating magnetic field (AMF). These magnetoliposomes were tested with two cancer cell lines, MDA-MB-231 and HeLa cells. First, 100 % of cellular uptake was achieved with a high cell survival (above 80 %), which is preserved (83 %) for doxorubicin loaded magnetoliposomes. Then, we demonstrate that doxorubicin release can be triggered by remote control, using a noninvasive external AMF for 1 hour, leading to a cell survival reduction of 20 %. Magnetic field conditions of 202 kHz and 30 mT seem to be enough to produce an effective heating avoiding drug degradation. In conclusion, these drug loaded magnetoliposomes prepared in one step could be used for drug release on demand at a specific time and place efficiently using an external AMF reducing or even eliminating side effects.
The
self-assembly of amyloid-β (Aβ) generates cytotoxic
oligomers linked to the onset and progression of Alzheimer’s
disease (AD). As many fundamental molecular pathways that control
Aβ aggregation are yet to be unraveled, an important strategy
to control Aβ cytotoxicity is the development of bioactive synthetic
nanotools capable of interacting with the heterogeneous ensemble of
Aβ species and remodel them into noncytotoxic forms. Herein,
the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers
with a precise number of Ga at their surface is described. It is shown
that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric
Aβ species at their Glu, Ala, and Asp residues, promoting their
remodeling into noncytotoxic aggregates in a process controlled by
the Ga units. The multivalent presentation of Ga on the dendrimer
surface enhances their ability to interact with Aβ, inhibiting
the primary and secondary nucleation of Aβ fibrillization and
disrupting the Aβ preformed fibrils.
Self-assembly structures of gemini surfactants are characterized, among others, for their low CMC. This characteristic could be due to great hydrophobic parts in their molecular structures. That availability could imply great stability of selfassembly structures or monolayers absorbed in an interface.The micellization behavior of two cationic gemini surfactants, α,ω-bis(S-alkyl dimethylammonium) alkane bromides, were studied by a modelization of dynamic surface tension (DST) experimental data and isothermal titration calorimetry (ITC) measurements. The adsorption data at the air/water interface was taken through the analysis of the profile changes of a pendant drop. The thermodynamic characterization of the micellization process of the gemini surfactants was carried out using ITC. A model based on the Frumkin adsorption isotherm and the Ward-Tordai diffusion equation was developed to obtain the characteristic parameters of the adsorption without the need of using the Gibbs adsorption equation. Positive values of lateral interaction show good stability of the adsorbed monolayer. The ITC data were analyzed following a novel protocol based on the identification of the different energetic contributions and regimens observed in the titration enthalpograms from demicellization processes. The presence of exothermic peaks would explain the low values of CMC.
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