Molecular motions in chitosan studied by dielectric Relaxation spectroscopy

Neutralized and nonneutralized chitosan films subject to different thermal treatments were studied by dielectric relaxation spectroscopy from -130 to +150 °C in the frequency range between 20 Hz and 1 MHz. Two main relaxation processes, both arrhenian type, were detected: process I at temperatures below 0 °C with a mean activation energy of 49 ( 1 kJ mol-1, which has the characteristics of a secondary relaxation process related with local chain dynamics, and process II observable at higher temperatures with an activation energy of 94 ( 2 kJ mol-1, correlated with dc conductivity, which is found in dried polysaccharides systems. Process I is always observed in neutralized chitosan, but it is strongly depleted in the wet nonneutralized form. Although the location of process I is independent of NH2/NH3 + side group, process II deviates to higher temperatures with dryness in both chitosan forms, being located at lower temperatures in nonneutralized chitosan.FCT, Foundation for Science and Technology, through the POCTI (POCTI/CTM/47363/2002) and FEDER programs

Influence of natural deep eutectic systems in water thermal behavior and their applications in cryopreservation

Natural deep eutectic systems (NADES), which have applications as solvents for both engineering and life sci-ences, are mainly composed of sugars, aminoacids or organic acids. In this work NADES composed by glucose,urea and proline (G:U:P in a molar ratio of 1:1:1) and proline and glucose (P:G 5:3) were prepared and addedin different mass fractions to water.By differential scanning calorimetry it was verified as the crystallization tendency of water is modified even forlow fraction of NADES added. This is also observed by polarized optical microscopy which allowed followingthe formation of crystals with different crystalline morphologies as bulk water. Calorimetric data also shown asthe crystallization temperature decreases for all P:G mixtures and this shift is more accentuated for weight frac-tion of NADES higher than 0.5. Crystallization is totally suppressed for NADES fraction higher than 0.7.NADES/water mixtures cytotoxicity was evaluated in vitro, revealing that they are less toxic as compared withthe commonly used cryoprotective additives as dimethyl sulfoxide (DMSO). Additionally, cell viability testswith cell lines cryopreserved using DMSO and both the prepared NADES showed comparable viability.This work combines thermophysical data on NADES and evaluates itâ s in vitro performance, providing cues fortheir use in cryopreservation applications.European Union Horizon 2020 Program under the agreement number ERC-2016-CoG 725034 (ERC Consolidator Grant Des.solve). This research was also funded by PTDC/EQU-EQU/29851/2017. A. Paiva acknowledges the financial support from project IF/01146/2015 attributed within the 2015 FCT researcher program. This work was supported by the Associate Laboratory for Green Chemistry - LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020

Evidence of Strong Guest–Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41

Funding Information: This research was funded by the Associate Laboratory for Green Chemistry LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2019) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER—007265). This research was funded by the Interreg 2 Seas program 2014–2020, and co-funded by the European Regional Development Fund (FEDER) under subsidy contract 2S01-059_IMODE and 2S07-033_ Site Drug. This research was funded by the Program PHC PESSOA 2018 project nbr 4340/40868R. This research was funded by National Funds through FCT—Portuguese Foundation for Science and Technology, reference UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UIDB/50025/2020-2023, and PTNMR (ROTEIRO/0031/2013; PINFRA/22161/2016), co-financed by ERDF through COMPETE 2020, Portugal, POCI and PORL and FCT through PIDDAC (POCI-01-0145-FEDER-007688). M.C.C. acknowledges PTNMR&i3N for the researcher contract. T. Cordeiro acknowledges Fundação para a Ciência e a Tecnologia (FCT) for the scholarship SFRH/BD/114653/2016. I. Matos acknowledges FCT for the Investigator FCT contract IF/01242/2014/CP1224/CT0008. Publisher Copyright: © 2023 by the authors.A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.publishersversionpublishe

Interplay between Structure and Dynamics in Chitosan Films Investigated with Solid-State NMR, Dynamic Mechanical Analysis, and X-ray Diffraction

Modern solid-state NMR techniques, combined with X-ray diffraction, revealed the molecular origin of the difference in mechanical properties of self-associated chitosan films. Films cast from acidic aqueous solutions were compared before and after neutralization, and the role of the counterion (acetate vs Cl⁻) was investigated. There is a competition between local structure and long-range order. Hydrogen bonding gives good mechanical strength to neutralized films, which lack long-range organization. The long-range structure is better defined in films cast from acidic solutions in which strong electrostatic interactions cause rotational distortion around the chitosan chains. Plasticization by acetate counterions enhances long-range molecular organization and film flexibility. In contrast, Cl⁻ counterions act as a defect and impair the long-range organization by immobilizing hydration water. Molecular motion and proton exchange are restricted, resulting in brittle films despite the high moisture content

Molecular Mobility and Strategies for Stabilization of Pharmaceutical Drugs

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Combining dielectric and thermal characterization techniques for studying the molecular dynamics of a pharmaceutical drug: S-ibuprofen

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Dielectric and thermal characterization of S-ibuprofen

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Characterization of the crystalline/amorphous phases of SIMVASTATIN: contribution from TSDC and DRS techniques

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Confinement effects on the dynamic behavior of poly(d,l‑lactic acid) upon incorporation in α‑cyclodextrin

Inclusion complexes (ICs) composed of α-cyclodextrin (α-CD) and poly(D,L-lactic acid) (PDLLA), with 10/24 (IC1) and 15/46 (IC2) (% w/ w) of PDLLA incorporated/initial PDLLA weight percentage, were prepared and characterized mainly by dielectric relaxation spectroscopy (DRS). Bulk PDLLA was also analyzed for comparison. DRS was revealed to be a suitable tool to distinguish the dynamical response of the PDLLA regions constrained in between α-CD channels from the fraction incorporated inside channels. While the cooperative α-process undergoes a dramatic depletion shifting to higher temperatures (∼4.5 °C) for the PDLLA interchannels portion, it is suppressed for PDLLA chains inside pores. It was demonstrated that the broad secondary relaxation of bulk PDLLA is the Johari−Goldstein process (βJGprocess). The detection of its analogue in the ICs at higher frequencies, to a greater extent in IC1, is interpreted as a true confinement effect where the dimensions of the α-CD channels interfere with the length scale of the βJG-process. The limit predicted in the framework of the coupling model, where the α-relaxation transforms in the βJG-process, seems to be reached in the ICs. Furthermore, it was found that the length scale of the additional γ process only detected in the ICs is inferior to inter- or intrachannel dimensions.Portuguese Foundation for Science and Technology (FCT) for financial support through the PTDC/FIS/115048/2009 project. M. T. Viciosa also thanks FCT for the postdoctoral grant SFRH/BPD/39691/2007

Use of SBA-15 silica matrices to stabilize an ionic liquid/API for drug delivery applications

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