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The number of the cyclodextrin-containing drug formulations on the market has been continuously growing since the first drug (prostaglandin E1 formulated with α-cyclodextrin) was launched in Japan in 1976. We have collected a list of drugs from various sources available on the internet to find 130 approved pharmaceutical ingredients formulated with either parent cyclodextrins or their hydroxypropyl, sulfobutyl, random methylated or sulfolipo derivatives. We have sorted the drug products according to the cavity size of the cyclodextrins, the administration route and dosage forms.

A tanulmány célja a duális és a hagyományos képzésben részt vevő hallgatók szakmai gyakorlatának vizsgálata. A kínálati oldalról (hallgatók) online kérdőíven, a keresleti oldalról (vállalatok) néhány vállalat HR-vezetőjével készített interjún keresztül gyűjtöttünk információt. Eredményeink azt mutatják, hogy a megkérdezett hallgatók többsége ismeri a duális képzést. A duális képzésben részt vevő hallgatók legfőbb motivációs tényezője rövid távon a szakmai gyakorlat megszerzése és a rendszeres jövedelem megléte. Hosszú távú céljaik között a professzionális szakmai ismeretek megszerzése és a jól fizető munka szerepel, míg a hagyományos képzésen tanulóknál a professzionális szakmai ismeretek megszerzése mellett egy jó csapatba kerülést tartották fontosnak. A megkérdezett vállalatok a duális képzésben tanulók szakmai gyakorlatához számos előnyt soroltak, úgymint a jobb mintaterv, a világos határidők és feltételek és a mélyebb szakmai tapasztalatszerzés.

Game theory has become an essential tool in the analysis of supply chains with multiple players who often have different interests. In this study, we use the game theory to examine the possibility of decision optimization and achieving equilibrium in the operation of the supply chain. Our goal is to determine the optimal agreement between the wholesaler and the retailer(s) to minimize the total cost in the supply chain in the given situation. The research method used in the study enriches the literature on the topic by linking the minimization of costs not to abstract evaluation metrics but to the stock order item size often calculated in real business as well. This facilitates the interpretation of the strategies and decision motivations used by the members of the supply chain.

Most of the organic compounds contaminating the environment can form inclusion complexes with cyclodextrins resulting in enhanced solubility (a benefit in soil remediation) or just the opposite: reduced mobility by sorption (a benefit in wastewater treatment). Combining biotechnologies with cyclodextrin, a renewable and biodegradable material, green environmental technologies of high efficiency were developed. For instance, the cyclodextrin-enabled soil washing/flushing technologies combined with bioremediation have been demonstrated in full-scale field experiments. The efficiency of tertiary wastewater treatment by sorption of non-biodegradable xenobiotics, such as residual pharmaceutics, was proved. The biofilm formation in fouling processes can be prevented or reduced either by applying cyclodextrin-based coatings or by manipulation of quorum sensing (bacterial communication) via capturing signal molecules.

International audience; The rise of emerging contaminants in waters challenges the scientific community and water treatment stakeholders to design remediation techniques that are simple, practical, inexpensive, effective, and environmentally friendly. Emerging contaminants include antibiotics, hormones, illicit drugs, endocrine disruptors, cosmetics, personal care products, pesticides, surfactants, industrial products, microplastics, nanoparticles, and nanomaterials. Removing those contaminants is not easy because classical wastewater treatment systems are not designed to handle emerging contaminants, and contaminants often occur as traces in complex organo-mineral mixtures. Here, we review advanced treatments for the removal of emerging contaminants in wastewater, with focus on adsorption-oriented processes using non-conventional adsorbents such as cyclo-dextrin polymers, metal-organic frameworks, molecularly imprinted polymers, chitosan, and nanocellulose. We describe biological-based technologies for the degradation and removal of emerging contaminants. Then, we present advanced oxidation processes as the most promising strategies because of their simplicity and efficiency.

Manapság a szervezeten belüli és szervezetek közötti munkaerőmozgások korát éljük. A vállalatok számára azonban nem jelent problémát az, hogy a távozó munkaerő helyére gyorsan találjanak naprakész ismeretekkel rendelkező új munkatársakat. A fejlett technológiai újítások révén piacvezető pozíciójáról sem kell lemondani egyetlen cégnek sem. Azonban, ha a vállalatnál felhalmozódott tudásának megtartására nem fektet különösebb hangsúlyt, különösen a kulcsemberek tekintetében, akkor piaci pozíciója veszélybe kerülhet. Ez fokozottan igaz akkor, amikor a távozó munkatárs tapasztalatáról, implicit vagy tacit tudásáról van szó, mivel ez jelenti az egyetlen olyan fenntartható versenyelőnyt, mely az üzleti élet többi szereplőjétől valóban megkülönbözteti a vállalatot. Jelen tanulmányban egy nagyobb témakört felölelő kutatás részeként lefolytatott részkutatást mutatnak be a szerzők. A vizsgálat középpontjában az átadható tudás módszertani kérdései és a tudás átadását támogató eszközök vizsgálata állt. A tanulmány célja azon eszközök azonosítása, csoportosítása, amellyel a tacit tudás átadásának fenntarthatósága bizonyíthatóan hosszú távon beépíthető a mai magyarországi vállalatok életébe.

Our paper explores the impacts and sustainability of remote and online education framework introduced as a result of the COVID-19 epidemic in the case of two subjects (Macroeconomics and International Economics) taught at the Faculty of Commerce, Hospitality and Tourism, Budapest Business School. In our study we focused on specific aspects of shifting from traditional in-class learning to online education at our university. The most important pillars of the shift were the online implementation of all lessons, communication and examinations. We analyzed the measures of the education change, the effects of the change on the final results of the students and introduced the experiences of our students and teachers in this period, reflecting on the principles of sustainability. The primary data required for the analysis were diaries maintained by teachers and information available through the electronic study systems supporting online learning (CooSpace, Neptun), as well as student and teacher questionnaires and teacher interviews. The results for both subjects show that, despite the unmodified difficulty level of the exam questions, student performance improved during the remote learning period, that is, the learning process complies with the principles of sustainability. The implications of the study are therefore as follows: the coronavirus changed the educational framework of our university; the performance of students improved on both subjects; preparation time for teachers has increased, exam preparation time for students has also increased; consequently, online solutions used in distance learning period have changed the attitudes of the students and teachers as well. In the absence of personal feedback opportunities, regular monitoring tools were positively received by students, however, digital inequalities and previously less common tasks were more challenging for them. The experiences of the first semester affected by the epidemic were and can be utilized in later semesters as well.

A WHO 2016-os Egészségjelentése alapján a dohányzás a második legjelentősebb egészségkockázatú viselkedés. Az Egészségügyi Világszervezet előrejelzései szerint 2025-2050 között előreláthatóan évi tíz millió ember hal majd meg dohányzás következtében. Ezért nem véletlen, hogy szakirodalom széles körben foglalkozik ezzel a jelenséggel. A megközelítések azonban zömében egészségügyi, pszichológia, morális vagy kriminológiai szempontból vizsgálják a kérdést. A különböző szenvedélybetegségek (addiktológiai kórképek) az egyénnek, valamint mikro-, és makrokörnyezetének komoly gazdasági és társadalmi gondot okoznak, mint például az érintett személyek gyógykezelése, a munkaképesség csökkenése, vagy a szenvedélybetegségekkel összefüggő családi tragédiák. Tanulmányunkban a dohánytermékek fogyasztásának hatásait elsősorban közgazdasági szempontból kívánjuk górcső alá venni. Célunk, hogy az említett területeken megkíséreljük feltárni ezeknek a termékcsoportoknak a termelésével, forgalmazásával, illetve fogyasztásával kapcsolatosan felmerülő társadalmi, gazdasági károkat és hasznokat. Ez utóbbiakat ritkán említik (vagy egyáltalán nem említik), pedig számos személy, vállalkozás, sőt maga a társadalom számára a szenvedélybetegségek nemcsak áldozati, hanem haszonelemeket is tartalmaznak. A cikk első részében azokat a közgazdasági elméleteket és ezekre épülő kérdéseket, felvetéseket mutatjuk be, amelyek köré e vizsgálatot fel kívánjuk építeni. Ezután az elérhető statisztikai adatok és a különböző szekunder kutatások alapján megpróbáljuk feltárni a dohánytermékekre vonatkozóan a fogyasztásukból származó társadalmi, gazdasági hasznokat és károkat/költségeket.

Cyclodextrins, natural oligosaccharides obtained from starch by enzymatic degradation, have been discovered 130 years ago by the pioneering work of the French pharmacist and chemist Antoine Villiers. These molecules still fascinate researchers and industrials because they are remarkable macrocyclic molecules with major impacts in chemistry, biology and health science. When we look at cyclodextrin chemistry today and reflect on how it has developed over the last five decades, no other scientist has been more determining, focused and inspiring than Professor Jozsef Szejtli. Indeed, among the list of prestigious researchers who have contributed to the development of cyclodextrins, Professor Szejtli played a fundamental role as an eminent scientist and a visionary. Since the mid-1950s, he has devoted his life to cyclodextrins, publishing more than 500 publications, including 106 patent applications. Professor Szejtli is internationally recognized for his outstanding contribution to the cyclodextrin science and considered to be the “Godfather of Cyclodextrins.” This paper is a tribute to his scientific oeuvre. After a brief overview of his personal life, some important works published by Professor Szejtli in more than fifty years of career were highlighted. For example, he was the first to synthesize the 14C labeled glucose-based β-cyclodextrin and published his oral metabolism. He was also the first to describe the acid hydrolysis of β-cyclodextrin and discovered that β-cyclodextrin formed inclusion complexes with hydrochloric acid. Professor Szejtli is the founder of International Cyclodextrin Symposia, the first of which was held in 1981 in Budapest.

Lately, economists and policymakers have been paying even closer attention to the hidden economy. Indeed, it makes a difference to the economy how much money goes into the state coffers. To uncover the hidden economy, however, it is necessary to be familiar with its nature and manifestations. In this paper, with the aid of previous research and literature, we attempt to illustrate the characteristics of the hidden economy in Hungary before and after the regime change and to map out the steps that have been taken to uncover it. This publication was preceded by a systematic literature review on the definition, causes, and effects of the hidden economy, consisting of the collection of both data and literature related to the domestic hidden economy. The following summarizes the results from the synthesis of literature: The Hungarian hidden economy existed even before the regime change and took a variety of different forms. These include tips, bribes, informal payments, unauthorized work and patchwork, moonlighting, unauthorized rental of real estate, use of the social property for personal gain, gains from the infringement of customs and exchange law, tax fraud by craftsmen and retailers, theft of public property, and corruption. Since 1990, not only have the dynamics of the hidden economy strengthened, but its types of activities have changed significantly as well. These include, but are not limited to: omitting a portion of revenue from the register; recognizing non-incurred material production costs among expenditures; including an excessive portion of personal household maintenance costs among production costs; organizing business and study trips abroad; finder’s fee; end-of-year depreciation or ‘transfer’ of inventories; wages of registered employees paid out of pocket; employment of unreported employees; parallel company formation; the economic activity of unincorporated individuals and the income generated thereby. The following are among the concrete steps taken in recent years to uncover the Hungarian hidden economy: the temporary employment booklet; the simplified entrepreneurial tax; the Electronic Trade and Transport Control System; online cash registers; the connection of vending machines to the tax office., peer-reviewed

Tanulmanyunkban a rejtett gazdasag szisztematikus szakirodalmi attekinteset kisereltuk meg kozel szaz magyarorszagi es nemzetkozi mű feldolgozasa alapjan. A tanulmany harom terulet vizsgalatat tűzte ki celul: fogalmi megkozelitesek, a rejtett gazdasag kialakulasanak okai es a rejtett gazdasag hatasai. Modszerunk egy adott terulet szakirodalmanak szisztematikus, teljes korű feldolgozasa volt. Elmondhato, hogy a kozel negyven elnevezes es a szamtalan fogalmi meghatarozas nem teszi lehetőve egy egyseges definicio megalkotasat, ennek oka elsősorban az, hogy egy konkret orszag tobbeves attekintesekor sem biztos, hogy ugyanazok a terminusok ugyanazokat az elemeket tartalmazzak. A rejtett gazdasag okai kozott leggyakrabban az ado- es jarulekrendszer, az allami burokracia kiterjedtsege es hatekonysaga, valamint a szabalyozasi kornyezet szerepelt. A rejtett gazdasag okai es hatasai szorosan osszefuggnek, osszetett hatast gyakorolva egymasra. Journal of Economic Literature (JEL) kod: E26.

As remdesivir, the first FDA-approved drug for SARS-CoV-2 infection, can be used only for hospitalized patients due to intravenous administration, there is an urgent need of effective oral antiviral formulations to be used at early stage of infection in an outpatient setting. The present paper reports on the comparative pharmacokinetics of the electrospun nanofiber remdesivir/sulfobutyl ether beta-cyclodextrin formulation after intravenous and buccal administration. It was postulated that oral transmucosal administration avoids remdesivir from metabolic transformation and intact remdesivir can be detected in plasma, but only the active metabolite GS-441524 could be experimentally detected at a significantly lower plasma level, than that provided by the intravenous route. In buccally treated animals, the metabolite GS-441524 appeared only at 1 h after treatment, while in intravenously treated animals, GS-441524 was possible to quantify even at the first time-point of blood collection. Further optimization of formulation is required to improve pharmacokinetics of remdesivir-sulfobutyl ether beta-cyclodextrin formulation upon buccal administration.

International audience; Water pollution by emerging contaminants has become a major source of concern and a priority for society and public authorities. Emerging contaminants are a group of natural and synthetic chemicals and biological agents that are not routinely monitored or regulated in the environment and may have known or suspected adverse effects on the environment and human health. The list of these substances is particularly long and includes pharmaceuticals, personal care products and cosmetics, pesticides, surfactants, industrial products and additives, nanoparticles and nanomaterials, and pathogens. Many emerging contaminants are released continuously into the environment and can cause chronic toxicity even at low concentrations, endocrine disruption in humans and aquatic life, and the development of antibiotic resistant bacteria. It is therefore necessary to mobilize efforts to protect human health and biodiversity.Two of the main sources of emerging contaminants are wastewater treatment discharges and agricultural practices. However, conventional wastewater treatment plants have not been designed to remove such contaminants. It is therefore important to develop effective treatment methods capable of eliminating the parent emerging molecules and their metabolites. This is a difficult and challenging task because most of emerging contaminants are recalcitrant substances. The methods must also target not only water chemicals but also water microbiols in order to reduce and eliminate the toxicity and impact of the treated wastewater. During the past two decades, several physical, chemical and biological technologies have been proposed for emerging contaminant removal. Each technology has its own advantages and constraints not only in terms of cost, but also in terms of efficiency, feasibility, and environmental impact. However, among the various treatment processes currently cited for wastewater treatment, only few are commonly employed by the industrial sector for technological and economic reasons. Extensive research on this topic highlights the growing interest of scientists in developing treatment systems that are increasingly effective in removing mixtures of trace pollutants, simple to implement from a technological point of view, economically viable and environmentally friendly, with little or no impact on the environment.The objective of this chapter is to present the recent state of knowledge on the advanced treatments proposed for the removal of emerging contaminants in wastewater when they are present in trace amounts in wastewater. After generalconsiderations on wastewater treatment plant, the first part is focused on adsorption-oriented processes using conventional (activated carbon, clays) or non-conventional (cyclodextrin polymers, metal-organic frameworks, molecularly imprinted polymers, chitosan, nanocellulose) adsorbents. Biosorbents such as cyclodextrin bead polymers have great potential in environmental applications although they are still at the laboratory study stage. The second part presents examples of biological-based technologies for the degradation and elimination of emerging contaminants. Selected biological approaches include constructed wetlands, biomembrane reactors, strategies based on the use of algae, fungi and bacteria, and enzymatic degradation. The third part briefly presents the membrane filtration strategy that is already used as a tertiary treatment. The final part is focused on advanced oxidation processes that also represent one of the most promising strategies because of their simplicity and efficiency.

Off-flavors and off-taste are taints in food products caused by the presence of undesirable compounds originated from the raw material or from changes during processing and storage in consequence of excessive heating, exposure to sunlight, microbial activity, etc. Cyclodextrins not only protect the encapsulated components from the deteriorating effect of oxygen, light and temperature in this way preventing the formation of off-taste and off-flavor, but they can be also used to remove the components of unpleasant taste or odor, such as bitter substances from orange and grapefruit juices, off-flavors from old rice, bitterness of over-roasted coffee, fishy taste of omega-3 fatty acids and beany odor and taste from soybean products. The bitter taste and astringency of protein hydrolysates can be completely masked. Fat-containing foods can be preserved from both oxidative and microbial rancidity via complexation of fatty acids with cyclodextrin or by applying antioxidant and/or antimicrobial agents encapsulated by cyclodextrin. In this chapter we show the methods used for characterization of off-flavor and off-taste, explore the possible causes of malodor and disagreeable taste, and demonstrate how cyclodextrin can help via several examples.

Cyclodextrins are widely used excipients for increasing water-solubility, delivery and bioavailability of lipophilic drugs. By using fluorescent cyclodextrin derivatives, we showed previously that cyclodextrins are able to enter Caco-2 intestinal cells by endocytosis, but the influence of different fluorescent labeling on the same cyclodextrin derivative has not been studied. The consequences of the cellular internalization of cyclodextrins have not been revealed yet either. The aims of this study were to compare the cellular internalization of fluorescein- and rhodamine-labeled (2-hydroxypropyl)-, (HPBCD) and randommethyl-&beta, cyclodextrins (RAMEB) and to investigate the intracellular effects of these derivatives on Caco-2 cells. Stimulation of the NF-kappa B pathway and autophagy and localization of these derivatives in lysosomes were tested. The endocytosis of these derivatives was examined by fluorescence microscopy and flow cytometry. Both fluorescein- and rhodamine-labeled derivatives entered the cells, therefore the type of the fluorescent labeling did not influence their internalization. Cyclodextrin pretreatment did not activate the translocation of the p65 subunit of the NF-kappa B heterodimer into the cell nuclei from the cytoplasm. After HPBCD or RAMEB treatment, formation of the autophagosomes did not increase compared to the control sample and at the same time these derivatives could be detected in lysosomes after internalization.

International audience; Cyclodextrins are a group of cyclic oligosaccharides obtained by enzymatic degradation of starch. They are remarkable macrocyclic molecules that have led major theoretical and practical advances in chemistry, biology, biochemistry, health science, and agriculture. Their molecular structure is composed of a hydrophobic cavity that can encapsulate other compounds to form inclusion complexes through host-guest interactions. This unique feature is at the origin of many applications. Cyclodextrins and their derivatives have a wide variety of practical applications in almost all sectors of the industry, including pharmacy, medicine, foods, cosmetics, chromatography, catalysis, biotechnology, and the textile industry. Villiers published the first reference to cyclodextrins in 1891, and since then, these molecules have continued to fascinate academia and industry. Currently, more than 2000 publications on cyclodextrins are published each year. On the occasion of the 130th anniversary of their discovery, in this review, we present an historical overview of the development and applications of cyclodextrins. First, we present the discovery and first chemical studies on cyclodextrins. Then, the main results obtained during the 1911-1970 exploration period are discussed. A third part presents the historical landmarks in the development of cyclodextrins from 1970 to the present day.

In contrary to traditional packaging which serves merely as passive barrier designed to delay adverse effects of the environment on packaged item, active food packaging aims to protect the product against oxidation, moisture, light and microbiological contamination during transport, storage, sale and use. Active packaging may contain various functional additives such as antioxidants, antibacterial, antifungal and ripening agents to reduce food degradation and extend shelf life. These additives might be unstable and get released too fast. Cyclodextrins can help to improve these properties via inclusion complex formation. This chapter intends to give an overview on application of cyclodextrins and their complexes in active packaging to show the usefulness of these cyclic carbohydrates in many roles improving the performance of packaging. Packaging may contain “empty” cyclodextrins capable of entrapping migrating compounds, reducing release of plasticizers and other harmful compounds, scavenging odor and removing unwanted components. The other types of packaging contain cyclodextrins “filled” with actives (these are inclusion complexes) providing protection for the encapsulated preservatives from loss on heat during preparation and ensuring controlled-release for a long time. The trigger for release is humidity, making these materials especially useful for packaging moisture-containing food items. Flavor-releasing films, antimicrobial and antioxidant packaging represent the main fields of applications of cyclodextrin complexes incorporated into packaging.

The limited bioavailability of the highly hydrophobic natural compound, curcumin with wide range of beneficial bioactivity is still a challenge. Self-association type systems of polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymers (Pluronic) were applied to enhance the aqueous solubility of curcumin. Comparison of four Pluronics (94, 105, 127,108) with different compositions led to the conclusion that solubilization capacity is maximum for Pluronic 105 with intermediate polarity (hydrophilic/lipophilic balance (HLB) = 15) possessing the optimum balance between capacity of hydrophobic core of the micelle and hydrophilic stabilizing shell of the associate. Curcumin concentration in aqueous solution was managed to increase 105 times up to 1&ndash, 3 g/L applying Pluronic at 0.01 mol/L. Formation of a host&ndash, guest complex of cyclodextrin as another way of increasing the curcumin solubility was also tested. Comparing the(2-hydroxypropyl)-&alpha, &beta, and &gamma, cyclodextrins (CD) with 6, 7 and 8 sugar units and their polymers (poly-&alpha, CD, poly-&beta, CD, poly-&gamma, CD) the &gamma, CD with the largest cavity found to be the most effective in curcumin encapsulation approaching the g/L range of concentration. The polymer type of the CDs presented prolonged and pH dependent release of curcumin in the gastrointestinal (GI) system modelled by simulated liquids. This retarding effect of polyCD was also shown and can be used for tuning in the combined system of Pluronic micelle and polyCD where the curcumin release was slower than from the micelle.

We report herein on a novel water-soluble β-cyclodextrin-branched polymer covalently integrating a fluorescein moiety and a nitric oxide (NO) photodonor within its macromolecular skeleton. Photoexcitation with visible light induces the parallel activation of the two chromophores, which results in the green fluorescence emission suitable for imaging accompanied by NO release for therapy. In fact, this polymer internalizes in squamous carcinoma cancer cells in vitro, visualized by fluorescence microscopy, and induces cell mortality as result of the NO photo-decaging. The non-covalent drug delivery capability of this new material is also demonstrated using a hydrophobic photosensitizer for photodynamic therapy as a probe.

Two β-cyclodextrin derivatives randomly appended on the primary face with both the nitric oxide (NO) photodonor 4-nitro-3-(trifluoromethyl)aniline and a mannose or α(1→2)mannobioside residue are reported to construct targeted NO photoreleasing nanocarriers. 2D ROESY and PGSE NMR suggested supramolecular homodimerization in water by inclusion of the nitroaniline group into the facing macrocycle cavities. Isothermal titration calorimetry on their concanavalin A lectin binding showed an exothermic binding event to the lectin and an endothermic process during the dilution of the conjugates. Both α(1→2)mannobioside and the nitroaniline moieties significantly enhanced the binding to the lectin. These effects might arise from a better fit within the carbohydrate-recognition site in the former case and a multivalent effect caused by homodimerization in the latter. Direct detection of NO by amperometric technique shows that both β-cyclodextrin derivatives release this radical upon excitation with visible light with higher efficiency than the unfunctionalized NO photodonor.

Steroids are abundant in living organisms and are responsible for various biological functions. They are good candidates for inclusion complexes formation with cyclodextrins; therefore, plenty of literature describes these complexes and their application in various fields. There are, however, hardly any reviews summarizing this tremendous amount of information. Here, we review steroid drugs in relation to their complexation with cyclodextrins, highlighting the effect of cyclodextrin–steroid interaction on the solubility, stability and bioavailability of the entrapped steroid drugs. We have collected data on the changes in the pharmacokinetics of cyclodextrin-formulated steroid drugs designed for various routes of administration. We show some cyclodextrin-enabled steroid formulations introduced to the market. Sugammadex, the first cyclodextrin derivative approved as active pharmaceutical ingredient, which revolutionized anesthesia, is also discussed. Several examples demonstrate the catalysis and inhibition of various biotransformation reactions of steroids by cyclodextrin complexation used in biotechnology. The laboratory- and pilot-scale experiments for environmental application of cyclodextrin–steroid interaction are based on cyclodextrin-containing sorbents for capturing residual steroid drugs, such as contraceptives from purified wastewater.

Clofazimine (CLZ) is an antibiotic with a promising behavior against Gram-positive bacteria; however, the drug is completely insoluble in water and accumulates in fat tissues. We explored nanocarriers, labeled and not labeled with rhodamine, consisting of negatively charged sulfobutylether-beta-cyclodextrins for CLZ loading. A new oligomeric carrier was obtained cross-linking beta CyD with epichlorohydrin followed by sulfonation in a strongly alkaline aqueous medium. The oligomeric carrier has a MW of 53 kDa and forms small nanoparticles of a few tens of nm. With aqueous solutions containing a 25 mg/mL oligomeric carrier, we loaded up to 0.5 mg/mL of drug. The oligomers exhibited a 10-fold better loading capacity compared to monomers and formed nanoparticles with a size in the 20-60 nm range after drug loading. Circular dichroism confirmed encapsulation of the CLZ in the nanocarriers. All carriers with or without CLZ are not cytotoxic up to 1 mu M, while CLZ alone is highly cytotoxic at the same concentration. The drug has IC50 values below 100 nM against S. epidermidis. The same holds true also for clinical isolates of S. epidermidis, some displaying MDR So, the selectivity index significantly increased for CLZ/carrier systems compared to the drug alone. Taken all together, our results open new avenues for the clinical application of this antibiotic.

Benzylpenicillin is characterized by instability in aqueous media, low oral bioavailability, and short biological half-life. Since their degradation products can cause allergic reactions, β-lactam antibiotics are supplied as a powder for injection and require special precaution when stored and re-constituted in water. An efficient method for β-lactam stabilization in the aqueous environment could reduce allergic side effects and facilitate their handling. Previously we proposed that complexation with cyclodextrins (CDs) is a way to achieve this goal. The purpose of the present study was to investigate the effect of methylation of CD on the chemical stability of benzylpenicillin. Kinetic studies revealed that degree of methylation of the CD molecule determines whether the CD has destabilizing or stabilizing effect on the β-lactam. The fully methylated βCD derivative Trimeb stabilizes benzylpenicillin while partial methylation of βCD only decreases to some extent the catalytic effect of native βCD. The complexes of all investigated CDs were also studied by DSC, FT-IR and NMR spectroscopy.

Meropenem is a carbapenem antibiotic with ultrabroad spectrum of activity and active against bacterial strains resistant to other antibiotics. The drug is characterized by fast renal elimination and high instability in aqueous solution where it undergoes β-lactam ring opening with consequent loss of biological activity. The purpose of this study was to develop cyclodextrin (CD) based nanoparticles (NPs) for increased meropenem bioavailability and stability in aqueous solutions. Self-assembly nanoparticles are formed by carboxymethylcellulose (CMC) and quaternary amino βCD polymer (QAβCDp), NPs of CMC-QAβCDp with relatively narrow size distribution profile are spontaneously formed in aqueous solution. The NPs were characterized by UV-VIS spectroscopy, DLS size measurements, Zeta potential and NMR spectroscopy. The kinetic stability studies revealed that meropenem loaded NPs can slow down the β-lactam antibiotic hydrolysis at room temperature by nearly 30% while at 4 °C the hydrolysis is 63% slower. The NPs with mean hydrodynamic diameter of about 135 nm displayed size stability during three-month storage at 4 °C. Incorporation of meropenem into the NPs increased the drug permeation through semi-permeable membranes suggesting that the NPs could have positive effect on meropenem permeation through biological membranes.

Ethionamide (ETH) is a second line antitubercular drug suffering from poor solubility in water and strong tendency to crystallize. These drawbacks were addressed by loading ETH in β-cyclodextrin (βCyD)-based carriers. The drug was incorporated in a molecular state avoiding crystallization even for long-term storage and obtaining a tenfold increased solubility up to 25 mM. The binding of ETH to polymeric βCyD nanoparticles (pβCyD NPs) was investigated in neutral aqueous medium by means of solubility phase diagrams, circular dichroism (CD) and UV–vis absorption and compared with the corresponding βCyD monomer. The binding constants and the absolute CD spectra of the drug complexes were determined by global analysis of multiwavelength data from spectroscopic titrations. The spectroscopic and photophysical properties of the complexes evidenced an alcohol-like environment for ETH included in the cavity. Additionally, ETH was found to be located not only in βCyD cavities, but also in confined microdomains inside the crosslinked NPs. This double modality of complexation together with a slightly higher binding constant makes the utilization of pβCyD NPs preferable over the monomeric βCyDs. In order to pave the way to future in vitro experiments, fluorescein labeled pβCyDs were synthesized. Interestingly the FITC labeling did not hamper the encapsulation of ETH and the drug improved the fluorescent signal of FITC molecules. The βCyD-based carriers appeared as versatile “green” systems for efficient incorporation and future delivery of ETH.

Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole - small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP. Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and α-CD proved to be very effective (60-100% retained drug amount). Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine.

Background Metal-organic framework nanoparticles (nanoMOFs) are biodegradable highly porous materials with a remarkable ability to load therapeutic agents with a wide range of physico-chemical properties. Engineering the nanoMOFs surface may provide nanoparticles with higher stability, controlled release, and targeting abilities. Designing postsynthetic, non-covalent self-assembling shells for nanoMOFs is especially appealing due to their simplicity, versatility, absence of toxic byproducts and minimum impact on the original host-guest ability. Methods In this study, several β-cyclodextrin-based monomers and polymers appended with mannose or rhodamine were randomly phosphorylated, and tested as self-assembling coating building blocks for iron trimesate MIL-100(Fe) nanoMOFs. The shell formation and stability were studied by isothermal titration calorimetry (ITC), spectrofluorometry and confocal imaging. The effect of the coating on tritium-labeled AZT-PT drug release was estimated by scintillation counting. Results Shell formation was conveniently achieved by soaking the nanoparticles in self-assembling agent aqueous solutions. The grafted phosphate moieties enabled a firm anchorage of the coating to the nanoMOFs. Coating stability was directly related to the density of grafted phosphate groups, and did not alter nanoMOFs morphology or drug release kinetics. Conclusion An easy, fast and reproducible non-covalent functionalization of MIL-100(Fe) nanoMOFs surface based on the interaction between phosphate groups appended to β-cyclodextrin derivatives and iron(III) atoms is presented. General significance This study proved that discrete and polymeric phosphate β-cyclodextrin derivatives can conform non-covalent shells on iron(III)-based nanoMOFs. The flexibility of the β-cyclodextrin to be decorated with different motifs open the way towards nanoMOFs modifications for drug delivery, catalysis, separation, imaging and sensing. This article is part of a Special Issue entitled “Recent Advances in Bionanomaterials” Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.

The research on cyclodextrin started at the beginning of the 1970s at Cyclodextrin Research Laboratory of Chinoin Pharmaceutical and Chemical Works Co. Ltd. in Hungary. Professor Jozsef Szejtli, the leading scientist of the field, soon recognized the importance of production. According to his estimations, market demands were likely to reach 1000–2000 tons per year. In early times, cyclodextrins were available on the market only as fine chemicals in few gram quantities. Cyclodextrins were produced by enzymatic degradation and subsequent cyclization of starch, forming a mixture of acyclic and cyclic dextrins. The converting enzyme, cyclodextrin glucosyltransferase, could be found in some strains of soil microorganisms. The industrial scale production of enzyme possessing high cyclizing activity was an essential demand for the high capacity cyclodextrin production. It was also aimed to develop an appropriate starch conversion technology capable to produce alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin at high yields by the means of processed enzyme.

Cyclodextrins are cyclic oligosaccharides obtained by enzymatic degradation of starch. They are remarkable macrocyclic molecules that have led major theoretical and practical advances in chemistry, biology, biochemistry, health science, and agriculture. Their molecular structure is composed of a hydrophobic cavity that can encapsulate other substances to form inclusion complexes through host-guest interactions. This unique feature is at the origin of many applications. Cyclodextrins and their derivatives have a wide variety of practical applications in almost all sectors of the industry, including pharmacy, medicine, foods, cosmetics, chromatography, catalysis, biotechnology, and the textile industry.

Cyclodextrins, natural oligosaccharides obtained from starch by enzymatic degradation, have been discovered more than 129 years ago by the pioneering work of the French pharmacist and chemist Antoine Villiers. These molecules still fascinate researchers and industrials because they are remarkable macrocyclic molecules with major impacts in chemistry, biology, and health science.