Cyclodextrins are cyclic oligosaccharides that have received special attention due to their cavity-based structural architecture that imbues them with outstanding properties, primarily related to ...their capacity to host various guest molecules, from low-molecular-mass compounds to polymers. Cyclodextrin derivatization has been always accompanied by the development of characterization methods, able to unfold complicated structures with increasing precision. One of the important leaps forward is represented by mass spectrometry techniques with soft ionization, mainly matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). In this context, esterified cyclodextrins (ECDs) benefited also from the formidable input of structural knowledge, thus allowing the understanding of the structural impact of reaction parameters on the obtained products, especially for the ring-opening oligomerization of cyclic esters. The current review envisages the common mass spectrometry approaches such as direct MALDI MS or ESI MS analysis, hyphenated liquid chromatography-mass spectrometry, and tandem mass spectrometry, employed for unraveling the structural features and particular processes associated with ECDs. Thus, the accurate description of complex architectures, advances in the gas phase fragmentation processes, assessment of secondary reactions, and reaction kinetics are discussed in addition to typical molecular mass measurements.
The reaction of diols with isocyanates, leading to mono-functional and di-functional prepolymers may be investigated using various characterization methods which show the overall conversion of ...isocyanate monomers. On the other hand, matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) polymer characterization can be employed to identify the monomer units, the end-group functionalities, molecular weight averages, and to determine the copolymer sequence. Herein, we focus on prepolymer synthesis using isophorone diisocyanate (IPDI), a widely used diisocyanate for prepolymers preparation, especially in waterborne polyurethane materials. Thus, the reaction between polyethylene glycol diol and IPDI was in-depth investigated by mass spectrometry to determine the influence of the reaction parameters on the prepolymer's structure. The relative content of the different functional oligomer species at given reaction times was determined in the reaction mixture. More specifically, the offline analysis revealed the influence of reaction parameters such as reaction temperature, the concentration of reactants, and the amount of dibutyltin dilaurate catalyst. The established MALDI MS analysis involved measurements of samples, first, directly collected from the reaction mixture and secondly, following derivatization with methanol. The obtained results revealed the effects of reaction parameters on the functionalization reaction with isocyanates, allowing to achieve a better reaction control.
Herein, we report the synthesis of inclusion complexes (ICs) based on 3,4-ethylenedioxythiophene (EDOT) with permethylated β-cyclodextrins (TMe-βCD) and permethylated γ-cyclodextrins (TMe-γCD) host ...molecules. To prove the synthesis of such ICs, molecular docking simulation, UV-vis titrations in water,
H-NMR, and H-H ROESY, as well as matrix-assisted laser desorption ionization mass spectroscopy (MALDI TOF MS) and thermogravimetric analysis (TGA) were carried out on each of the EDOT∙TMe-βCD and EDOT∙TMe-γCD samples. The results of computational investigations reveal the occurrence of hydrophobic interactions, which contribute to the insertion of the EDOT guest inside the macrocyclic cavities and a better binding of the neutral EDOT to TMe-βCD. The H-H ROESY spectra show correlation peaks between H-3 and H-5 of hosts and the protons of the guest EDOT, suggesting that the EDOT molecule is included inside the cavities. The MALDI TOF MS analysis of the EDOT∙TMe-βCD solutions clearly reveals the presence of MS peaks corresponding to sodium adducts of the species associated with the complex formation. The IC preparation shows remarkable improvements in the physical properties of EDOT, rendering it a plausible alternative to increasing its aqueous solubility and thermal stability.
Nanotechnology is the science of creating materials at the nanoscale by using various devices, structures, and systems that are often inspired by nature. Micro- and nanoparticles (MPs, NPs) are ...examples of such materials that have unique properties and can be used as carriers for delivering drugs for different biomedical applications. Chitosan (CS) is a natural polysaccharide that has been widely studied, but it has a problem with low water solubility at neutral or basic pH, which limits its processability. The goal of this work was to use a chemically modified CS with poly(ethylene glycol) methyl ether acrylate (PEGA) to prepare CS micronic and submicronic particles (MPs/NPs) that can deliver different types of antibiotics, respectively, levofloxacin (LEV) and Ciprofloxacin (CIP). The particle preparation procedure employed a double crosslinking method, ionic followed by a covalent, in a water/oil emulsion. The studied process parameters were the precursor concentration, stirring speeds, and amount of ionic crosslinking agent. MPs/NPs were characterized by FT-IR, SEM, light scattering granulometry, and Zeta potential. MPs/NPs were also tested for their water uptake capacity in acidic and neutral pH conditions, and the results showed that they had a pH-dependent behavior. The MPs/NPs were then used to encapsulate two separate drugs, LEV and CIP, and they showed excellent drug loading and release capacity. The MPs/NPs were also found to be safe for cells and blood, which demonstrated their potential as suitable drug delivery systems for biomedical applications.
Cyclodextrins have previously been proven to be active in the catalysis of cyclic ester ring-opening reactions, hypothetically in a similar way to lipase-catalyzed reactions. However, the way they ...act remains unclear. Here, we focus on β-cyclodextrin's involvement in the synthesis and characterization of β-cyclodextrin-oligocaprolactone (CDCL) products obtained via the organo-catalyzed ring-opening of ε-caprolactone. Previously, bulk or supercritical carbon dioxide polymerizations has led to inhomogeneous products. Our approach consists of solution polymerization (dimethyl sulfoxide and dimethylformamide) to obtain homogeneous CDCL derivatives with four monomer units on average. Oligomerization kinetics, performed by a matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) optimized method in tandem with
H NMR, revealed that monomer conversion occurs in two stages: first, the monomer is rapidly attached to the secondary OH groups of β-cyclodextrin and, secondly, the monomer conversion is slower with attachment to the primary OH groups. MALDI MS was further employed for the measurement of the ring-opening kinetics to establish the influence of the solvents as well as the effect of organocatalysts (4-dimethylaminopyridine and (-)-sparteine). Additionally, the mass spectrometry structural evaluation was further enhanced by fragmentation studies which confirmed the attachment of oligoesters to the cyclodextrin and the cleavage of dimethylformamide amide bonds during the ring-opening process.
Cyclodextrins (CDs) were used in the present study for the ring-opening oligomerization (ROO) of l-lactide (LA) in order to synthesize biodegradable products with possible applications in ...pharmaceutical and medical fields. The practical importance of ROO reactions may reside in the possibility of synthesizing novel CD derivatives with high purity due to the dual role played by CDs, the role of the initiator through the hydroxylic groups, and the role of the catalyst by monomer inclusion in the CD cavity. The analyzed compounds were CDs modified with oligolactides obtained through ROO reactions of l-lactide in dimethylformamide. The resulting CD isomeric mixtures were investigated using classical characterization techniques such as gel permeation chromatography and nuclear magnetic resonance. Moreover, advanced mass spectrometry (MS) techniques were employed for the determination of the average number of monomer units attached to the cyclodextrin and the architecture of the derivatives (if the monomer units were attached as a single chain or as multiple chains). Thus, fragmentation studies effectuated on two different instruments (ESI Q-TOF and MALDI TOF) allowed us to correlate the size of the oligolactide chains attached to the CD with the observed fragmentation patterns.
The influence of the hydroxyl groups (OH) type on the polyaddition processes of isocyanates represents a critical approach for the design of multicomponent polyurethane systems. Herein, to prove the ...effect of hydroxyl nature on both the isocyanate-OH polyaddition reactions and the structure/properties of the resulting networks, two structurally different cyclodextrins in terms of the primary and secondary groups’ ratio were analyzed, namely native β-cyclodextrin (CD) and its derivative esterified to the primary hydroxyl groups with oligolactide chains (CDLA). Thus, polyurethane hydrogels were prepared via the polyaddition of CD or CDLA to isophorone diisocyanate polyethylene glycol-based prepolymers (PEG-(NCO)2). The degradable character of the materials was induced by intercalating oligolactide short sequences into the polymer chains composing the polymer network. In order to establish the influence of the OH type, the synthesis of polyurethane hydrogels was analyzed by a rheological investigation of the overall system reactivity. Materials properties such as swelling behavior, thermal properties and hydrolytic degradation were influenced by the reaction feed. Specifically, the presence of primary OH groups leads to more compact networks with similar water uptake, disregarding the CD content, while the predominance of secondary OH groups together with the presence of oligolactide spacers leads to the fine tuning of the water swelling properties.
Chitosan (CS) crosslinking has been thoroughly investigated, but the chemical reactions leading to submicronic hydrogel formulations pose problems due to various physical/chemical interactions that ...limit chitosan processability. The current study employs the chemical modification of chitosan by Michael addition of poly (ethylene glycol) methyl ether acrylate (PEGA) to the amine groups to further prepare chitosan particulate hydrogels (CPH). Thus, modified CS is subjected to a double crosslinking, ionic and covalent, in water/oil emulsion. The studied process parameters are polymer concentration, stirring speed, and quantity of ionic crosslinker. The CPH were structurally and morphologically characterized through infrared spectroscopy, scanning electron microscopy, light scattering granulometry, and zeta potential, showing that modified CS allows better control of dimensional properties and morphology as compared with neat CS. Swelling properties were studied in acidic and neutral pH conditions, showing that pH-dependent behavior was maintained after grafting and double crosslinking. The applicability of the prepared materials was further tested for drug loading and in vitro delivery of levofloxacin (LEV), showing excellent capacity. CPH were found to be cyto- and hemocompatible demonstrating their potential for effective use as a controlled release system for different biomedical applications.
The materials used for the preparation of electrospun mats exhibit a large variety. Among them, cyclodextrins (CDs) and their derivatives have received thorough attention. Herein, we focus on the ...preparation of electrospun fibers based on biodegradable cyclodextrin-oligolactide (CDLA) derivatives, which may be qualified as polymer-free cyclodextrin. CDLA was prepared by ring opening of L-lactide initiated by the β-cyclodextrin. A clear structural image of the high-purity CDLA product was proved by MALDI MS. Preparation of the electrospun mats was optimized by taking into consideration the electrospinning parameters such as applied voltage, needle-to-collector distance, flow rate, the concentration of cyclodextrin solutions, and solvent type. The obtained electrospun fibers were morphologically characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). SEM allowed the optimization of the electrospinning process to obtain beadless fibers with submicronic diameters. Further analysis by TEM and SAXS revealed the inner structural features of the CDLA-based filaments. Our results showed that the high purity CDLA materials, structurally well-defined at the molecular level, are suitable for the preparation of electrospun mats by using dimethylformamide or a water/acetonitrile mixture as electrospinning solvents, similar to lower molecular weight commercial cyclodextrin derivatives.
The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and ...pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.
PDF
