Enhancing Vitamin D3 Efficacy: Insights from Complexation with Cyclodextrin Nanosponges and Its Impact on Gut-Brain Axes in Physiology and IBS Syndrome.

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (ßNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut-brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut-brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.

Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects.

Iron overload in many brain regions is a common feature of aging and most neurodegenerative diseases. In this review, the causes, mechanisms, mathematical models, and possible therapies are summarized. Indeed, physiological and pathological conditions can be investigated using compartmental models mimicking iron trafficking across the blood-brain barrier and the Cerebrospinal Fluid-Brain exchange membranes located in the choroid plexus. In silico models can investigate the alteration of iron homeostasis and simulate iron concentration in the brain environment, as well as the effects of intracerebral iron chelation, determining potential doses and timing to recover the physiological state. Novel formulations of non-toxic nanovectors with chelating capacity are already tested in organotypic brain models and could be available to move from in silico to in vivo experiments.

The Difficulties in Emotion Regulation Scale-Dyadic version: A new tool for the evaluation of the dyadic dysregulation in couple relationships.

A new measure for assessing an individual's perception of the dyadic difficulties in emotion regulation with a romantic partner is tested. The Difficulties in Emotion Regulation Scale-Dyadic (DERS-D) was obtained by adapting some items of the previous Difficulties in Emotion Regulation Scale (DERS) to the dyadic context. The scale was administered both to a sample of university students (N = 835) to explore its factorial structure and to a convenience sample (N = 833) together with the DERS, the DERS-Positive, the Emotion Beliefs Questionnaire (EBQ), and the Emotion Regulation Questionnaire (ERQ) to confirm the factorial structure and to explore its construct validity. Results highlight that DERS-D measures two distinct features, namely the lack of dyadic awareness and the lack of dyadic clarity, and that configural invariance across genders was met. DERS-D subscales' internal consistency was high. The correlations between the DERS-D and the other measures demonstrated its construct and criterion validity. The promising nature of these results is discussed in light of the potential clinical and empirical uses of the DERS-D.

Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-ß protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

A New Blend of Litsea cubeba, Pinus mugo, and Cymbopogon winterianus Essential Oil Active as an Anti-tyrosinase Ingredient in Topical Formulations.

Tyrosinase is a target enzyme to be inhibited in order to reduce excessive melanin production and prevent typical age-related skin disorders. Essential oils are complex mixtures of volatile compounds, belonging mainly to monoterpenoids and sesquiterpenoids, which have been relatively little studied as tyrosinase inhibitors. Among the monoterpenoids, citral (a mixture of neral and geranial) is a fragrance compound in several essential oils that has shown interesting tyrosinase inhibitory activity. Although citral is listed as an allergen among the 26 fragrances in Annex III of the Cosmetics Directive 2003/15/EC, it can be safely used for the formulation of topical products in amounts that are not expected to cause skin sensitization, as shown by various commercially available products.The aim of this work was to evaluate two different formulations (oil/water emulsion, oily solution) containing a new combination of essential oils (Litsea cubeba, Pinus mugo, Cymbopogon winterianus) applied to the skin both in nonocclusive and partially occlusive modes. The blend is designed to reduce the concentration of citral to avoid potential skin reactions while taking advantage of the inhibitory activity of citral. Specifically, the amount of citral and other bioactive compounds (myrcene, citronellal) delivered through the skin was studied as a function of formulation and mode of application.The results show that an oil/water emulsion is preferable because it releases the bioactive compounds rapidly and minimizes their evaporative loss. In addition, semi-occluded conditions are required to prevent evaporation, resulting in higher availability of the bioactive compounds in viable skin.

Encapsulation in Oxygen-Loaded Nanobubbles Enhances the Antimicrobial Effectiveness of Photoactivated Curcumin.

In both healthcare and agriculture, antibiotic resistance is an alarming issue. Biocompatible and biodegradable ingredients (e.g., curcumin) are given priority in "green" criteria supported by the Next Generation EU platform. The solubility and stability of curcumin would be significantly improved if it were enclosed in nanobubbles (NB), and photoactivation with the correct wavelength of light can increase its antibacterial efficacy. A continuous release of curcumin over a prolonged period was provided by using innovative chitosan-shelled carriers, i.e., curcumin-containing nanobubbles (Curc-CS-NBs) and oxygen-loaded curcumin-containing nanobubbles (Curc-Oxy-CS-NBs). The results demonstrated that after photoactivation, both types of NBs exhibited increased effectiveness. For Staphylococcus aureus, the minimum inhibitory concentration (MIC) for Curc-CS-NBs remained at 46 µg/mL following photodynamic activation, whereas it drastically dropped to 12 µg/mL for Curc-Oxy-CS-NBs. Enterococcus faecalis shows a decreased MIC for Curc-CS-NB and Curc-Oxy-CS-NB (23 and 46 µg/mL, respectively). All bacterial strains were more effectively killed by NBs that had both oxygen and LED irradiation. A combination of Curc-Oxy-CS-NB and photodynamic stimulation led to a killing of microorganisms due to ROS-induced bacterial membrane leakage. This approach was particularly effective against Escherichia coli. In conclusion, this work shows that Curc-CS-NBs and Curc-Oxy-CS-exhibit extremely powerful antibacterial properties and represent a potential strategy to prevent antibiotic resistance and encourage the use of eco-friendly substitutes in agriculture and healthcare.

Enhanced Anti-Herpetic Activity of Valacyclovir Loaded in Sulfobutyl-ether-ß-cyclodextrin-decorated Chitosan Nanodroplets.

Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether ß-cyclodextrin (SBEßCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEßCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments.

Hard-Shelled Glycol Chitosan Nanoparticles for Dual MRI/US Detection of Drug Delivery/Release: A Proof-of-Concept Study.

This paper describes a novel nanoformulation for dual MRI/US in vivo monitoring of drug delivery/release. The nanosystem was made of a perfluoropentane core coated with phospholipids stabilized by glycol chitosan crosslinked with triphosphate ions, and it was co-loaded with the prodrug prednisolone phosphate (PLP) and the structurally similar MRI agent Gd-DTPAMA-CHOL. Importantly, the in vitro release of PLP and Gd-DTPAMA-CHOL from the nanocarrier showed similar profiles, validating the potential impact of the MRI agent as an imaging reporter for the drug release. On the other hand, the nanobubbles were also detectable by US imaging both in vitro and in vivo. Therefore, the temporal evolution of both MRI and US contrast after the administration of the proposed nanosystem could report on the delivery and the release kinetics of the transported drug in a given lesion.

Oxygen Nanocarriers for Improving Cardioplegic Solution Performance: Physico-Chemical Characterization.

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure.

Targeted chitosan nanobubbles as a strategy to down-regulate microRNA-17 into B-cell lymphoma models.

Introduction: MicroRNAs represent interesting targets for new therapies because their altered expression influences tumor development and progression. miR-17 is a prototype of onco-miRNA, known to be overexpressed in B-cell non-Hodgkin lymphoma (B-NHL) with peculiar clinic-biological features. AntagomiR molecules have been largely studied to repress the regulatory functions of up-regulated onco-miRNAs, but their clinical use is mainly limited by their rapid degradation, kidney elimination and poor cellular uptake when injected as naked oligonucleotides. Methods: To overcome these problems, we exploited CD20 targeted chitosan nanobubbles (NBs) for a preferential and safe delivery of antagomiR17 to B-NHL cells. Results: Positively charged 400 nm-sized nanobubbles (NBs) represent a stable and effective nanoplatform for antagomiR encapsulation and specific release into B-NHL cells. NBs rapidly accumulated in tumor microenvironment, but only those conjugated with a targeting system (antiCD20 antibodies) were internalized into B-NHL cells, releasing antagomiR17 in the cytoplasm, both in vitro and in vivo. The result is the down-regulation of miR-17 level and the reduction in tumor burden in a human-mouse B-NHL model, without any documented side effects. Discussion: Anti-CD20 targeted NBs investigated in this study showed physico-chemical and stability properties suitable for antagomiR17 delivery in vivo and represent a useful nanoplatform to address B-cell malignancies or other cancers through the modification of their surface with specific targeting antibodies.

Combining Blue Light and Yellow Curcumin to Obtain a "Green" Tool for Berry Preservation against Bacterial Contamination: A Preliminary Investigation.

Background: According to recent studies, tens of millions of tons of fruit are wasted each year in Europe in primary production and home/service consumption. Among fruits, berries are most critical because they have a shorter shelf life and a softer, more delicate, and often edible skin. Curcumin is a natural polyphenolic compound extracted from the spice turmeric (Curcuma longa L.) which exhibits antioxidant, photophysical, and antimicrobial properties that can be further enhanced by photodynamic inactivation of pathogens when irradiated with blue or ultraviolet light. Materials and methods: Multiple experiments were performed in which berry samples were sprayed with a complex of ß-cyclodextrin containing 0.5 or 1 mg/mL of curcumin. Photodynamic inactivation was induced by irradiation with blue LED light. Antimicrobial effectiveness was assessed with microbiological assays. The expected effects of oxidation, curcumin solution deterioration, and alteration of the volatile compounds were investigated as well. Results: The treatment with photoactivated curcumin solutions reduced the bacterial load (3.1 vs. 2.5 colony forming units/mL (UFC/ml) in the control and treated groups; p-value = 0.01), without altering the fruit organoleptic and antioxidant properties. Conclusions: The explored method is a promising approach to extend berries' shelf life in an easy and green way. However, further investigations of the preservation and general properties of treated berries are still needed.

Current Status and Trends in Nucleic Acids for Cancer Therapy: A Focus on Polysaccharide-Based Nanomedicines.

The efficacious delivery of therapeutic nucleic acids to cancer still remains an open issue. Through the years, several strategies are developed for the encapsulation of genetic molecules exploiting different materials, such as viral vectors, lipid nanoparticles (LNPs), and polymeric nanoparticles (NPs). Indeed, the rapid approval by regulatory authorities and the wide use of LNPs complexing the mRNA coding for the spark protein for COVID-19 vaccination paved the way for the initiation of several clinical trials exploiting lipid nanoparticles for cancer therapy. Nevertheless, polymers still represent a valuable alternative to lipid-based formulations, due to the low cost and the chemical flexibility that allows for the conjugation of targeting ligands. This review will analyze the status of the ongoing clinical trials for cancer therapy, including vaccination and immunotherapy approaches, exploiting polymeric materials. Among those nanosized carriers, sugar-based backbones are an interesting category. A cyclodextrin-based carrier (CALAA-01) is the first polymeric material to enter a clinical trial complexed with siRNA for cancer therapy, and chitosan is one of the most characterized non-viral vectors able to complex genetic material. Finally, the recent advances in the use of sugar-based polymers (oligo- and polysaccharides) for the complexation of nucleic acids in advanced preclinical stage will be discussed.

Developing New Cyclodextrin-Based Nanosponges Complexes to Improve Vitamin D Absorption in an In Vitro Study.

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, ßNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The ßNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.

Design, Characterization, and Biological Activities of Erythromycin-Loaded Nanodroplets to Counteract Infected Chronic Wounds Due to Streptococcus pyogenes.

Streptococcus pyogenes causes a wide spectrum of diseases varying from mild to life threatening, despite antibiotic treatment. Nanoparticle application could facilitate the foreign pathogen fight by increasing the antimicrobial effectiveness and reducing their adverse effects. Here, we designed and produced erythromycin-loaded chitosan nanodroplets (Ery-NDs), both oxygen-free and oxygen-loaded. All ND formulations were characterized for physico-chemical parameters, drug release kinetics, and tested for biocompatibility with human keratinocytes and for their antibacterial properties or interactions with S. pyogenes. All tested NDs possessed spherical shape, small average diameter, and positive Z potential. A prolonged Ery release kinetic from Ery-NDs was demonstrated, as well as a favorable biocompatibility on human keratinocytes. Confocal microscopy images showed ND uptake and internalization by S. pyogenes starting from 3 h of incubation up to 24 h. According to cell counts, NDs displayed long-term antimicrobial efficacy against streptococci significantly counteracting their proliferation up to 24 h, thanks to the known chitosan antimicrobial properties. Intriguingly, Ery-NDs were generally more effective (104-103 log10 CFU/mL), than free-erythromycin (105 log10 CFU/mL), in the direct killing of streptococci, probably due to Ery-NDs adsorption by bacteria and prolonged release kinetics of erythromycin inside S. pyogenes cells. Based on these findings, NDs and proper Ery-NDs appear to be the most promising and skin-friendly approaches for the topical treatment of streptococcal skin infections allowing wound healing during hypoxia.

Oral supplementation of solvent-free kynurenic acid/cyclodextrin nanosponges complexes increased its bioavailability.

Many nutraceuticals present problems due to their poor water solubility or stability, which prevents the final bioactivity achievement. For that reason, the oral administration of KYNA complexed with HPß-CD and ßNS-CDI nanosponges was evaluated in mice. The solvent-free technology was used to prepare the complexes in a complete comparison between kneading in ball milling and classical inclusion complex preparation. The solvent-free ones showed higher strength and efficiency with ball milling, considerably reducing time. A 50 mg KYNA/kg/day dosage was orally administered in formulations showing a higher bioavailability when the nutraceutical was complexed with ßNS-CDI compared to HPß-CD and free KYNA, respectively. Several antioxidant statuses demonstrated a higher global antioxidant level perfectly related to bioavailability. Finally, the formulation of KYNA reduced the temporal oxidative stress damage in the kidney and liver, making ßNS-CDI the best formulation. These results suggest an important future application of cyclodextrin-based nanosponges for the oral delivery of nutraceuticals and their stabilization.

Plasminogen activator-coated nanobubbles targeting cellbound ß2-glycoprotein I as a novel thrombus-specific thrombolytic strategy.

ß2-glycoprotein I (ß2-GPI) is a serum protein widely recognized as the main target of antibodies present in patients with antiphospholipid syndrome (APS). ß2-GPI binds to activated endothelial cells, platelets and leukocytes, key players in thrombus formation. We developed a new targeted thrombolytic agent consisting of nanobubbles (NB) coated with recombinant tissue plasminogen activator (rtPA) and a recombinant antibody specific for cell-bound ß2-GPI. The therapeutic efficacy of targeted NB was evaluated in vitro, using platelet-rich blood clots, and in vivo in three different animal models: i) thrombosis developed in a rat model of APS; ii) ferric chloride-induced mesenteric thrombosis in rats, and iii) thrombotic microangiopathy in a mouse model of atypical hemolytic uremic syndrome (C3-gain-of-function mice). Targeted NB bound preferentially to platelets and leukocytes within thrombi and to endothelial cells through ß2-GPI expressed on activated cells. In vitro, rtPA-targeted NB (rtPA-tNB) induced greater lysis of platelet-rich blood clots than untargeted NB. In a rat model of APS, administration of rtPA-tNB caused rapid dissolution of thrombi and, unlike soluble rtPA that induced transient thrombolysis, prevented new thrombus formation. In a rat model of ferric chloride triggered thrombosis, rtPA-tNB, but not untargeted NB and free rtPA, induced rapid and persistent recanalization of occluded vessels. Finally, treatment of C3-gain-of-function mice with rtPA-tNB, that target ß2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NB. Our findings suggest that targeting cell-bound ß2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APS-unrelated thrombotic conditions.

Hyper-Branched Cyclodextrin-Based Polymers as Anticoagulant Agents: In Vitro and In Vivo Studies.

This study tested the anticoagulant effect of cyclodextrin (CD) hyper-branched-based polymers (HBCD-Pols). These polymers were synthesized and tested for their coagulant characteristics in vitro and in vivo. Due to their polymeric structure and anionic nature, the polymers can chelate Ca2+, reducing the free quantity in blood. HBCD-Pol increased the blood clotting time, PT, and aPTT 3.5 times over the control, showing a better effect than even ethylenediaminetetraacetic acid (EDTA), as occured with recalcification time as well. A titration of HBCD-Pol and EDTA showed exciting differences in the ability to complex Ca2+ between both materials. Before executing in vivo studies, a hemocompatibility study was carried out with less than 5% red blood cell hemolysis. The fibrinogen consumption and bleeding time were analyzed in vivo. The fibrinogen was considerably decreased in the presence of HBCD-Pol in a higher grade than EDTA, while the bleeding time was longer with HBCD-Pols. The results demonstrate that the anticoagulant effect of this HBCD-Pol opens novel therapy possibilities due to the possible transport of drugs in this carrier. This would give combinatorial effects and a potential novel anticoagulant therapy with HBCD-Pol per se.

Medium-high frequency sonication dominates spherical-SiO2 nanoparticle size.

Spherical SiO2 nanoparticles (SSNs) have been inventively synthesized using the Stöber method with sonication at medium-high frequencies (80, 120, and 500 kHz), aiming to control SSN size and shorten reaction time. Compared to the conventional method, such sonication allowed the Stöber reaction complete in 20-60 min with a low molar ratio of NH4OH/tetraethyl orthosilicate (0.84). The hydrodynamic diameters of 63-117 nm of SSNs were obtained under sonication with 80, 120, and 500 kHz of ultrasonic frequencies. Moreover, the SSNs obtained were smaller at 120 kHz than at 80 kHz in a multi-frequencies ultrasonic reactor, and the SSN size decreased with increasing ultrasonic power at 20 °C, designating the sonochemical unique character, namely, the SSN-size control is associated with the number of microbubbles originated by sonication. With another 500 kHz ultrasonic bath, the optimal system temperature for producing smaller SSNs was proven to be 20 °C. Also, the SSN size decreased with increasing ultrasonic power. The smallest SSNs (63 nm, hydrodynamic diameter by QELS, or 21 nm by FESEM) were obtained by sonication at 207 W for 20 min at 20 °C. Furthermore, the SSN size increased slightly with increasing sonication time and volume, favoring the scale-up of SSNs preparation. The mechanisms of controlling the SSN size were further discussed by the radical's role and effects of ammonia and ethanol concentration.

L-Arginine-Derived Polyamidoamine Oligomers Bearing at Both Ends ß-Cyclodextrin Units as pH-Sensitive Curcumin Carriers.

The aza-Michael polyaddition of L-arginine and N,N'-methylene-bis-acrylamide gives the biocompatible and easily cell-internalized polyamidoamine ARGO7. By controlled synthesis, two ARGO7 oligomers, namely a trimer and a pentamer, bearing acrylamide terminal units, were obtained as precursors of the ß-cyclodextrin-end-terminated oligomers P3 and P5, which have been shown to encapsulate curcumin at both pH 7.4 and 4.5. After lyophilization, P3- and P5-curcumin complexes gave stable water solutions. The apparent solubility of encapsulated curcumin was in the range 20-51 µg mL-1, that is, three orders of magnitude higher than the water solubility of free curcumin (0.011 µg mL-1). The drug release profiles showed induction periods both at pH levels 4.5 and 7.4, suggesting a diffusive release mechanism, as confirmed by kinetic studies. The release rate of curcumin was higher at pH 7.4 than at pH 4.5 and, in both cases, it was higher for the P5 complex. Encapsulated curcumin was more photostable than the free drug. Molecular mechanics and molecular dynamics simulations explain at atomistic level the formation of aggregates due to favorable van der Waals interactions. The drug molecules interact with the external surface of carriers or form inclusion complexes with the ß-cyclodextrin cavities. The aggregate stability is higher at pH 4.5.

Dextrin-Based Nanohydrogels for Rokitamycin Prolonged Topical Delivery.

Macrolides are widely used antibiotics with a broad spectrum of activity. The development of drug carriers to deliver this type of antibiotics has attracted much research. The present study aims at developing new swellable dextrin-based nanohydrogels for the topical delivery of rokitamycin, as model macrolide. Rokitamycin is a synthetic analogous of macrolides with advantageous characteristics as far as bacterial uptake and post-antibiotic effect are concerned. It is also indicated for the treatment of severe infections caused by Acanthamoeba and for topical infections. The nanohydrogels have been prepared from two types of cross-linked polymers obtained by using ß-cyclodextrin or Linecaps® was provided by the Roquette Italia SPA (Cassano Spinola, Al, Italy) as building blocks. The cross-linked polymers have been then formulated into aqueous nanosuspensions refined and tuned to achieve the incorporation of the drug. Cross-linked ß-cyclodextrin (ß-CD) and Linecaps® (LC) polymers formed dextrin-based nanohydrogels with high swelling degree and mucoadhesion capability. Rokitamycin was loaded into the nanohydrogels displaying an average size around 200 nm with negative surface charge. In vitro kinetic profiles of free and loaded drug in nanohydrogels were compared at two pH levels. Interestingly, a sustained and controlled release was obtained at skin pH level due to the high degree of swelling and a pH responsiveness possibly. The results collected suggest that these nanohydrogels are promising for the delivery of rokitamycin and may pave the way for the topical delivery of other macrolide antibiotics.