Magnetic hydrogel based on xylan, poly (acrylic acid), and maghemite as adsorbent material for methylene blue adsorption: experimental design, kinetic, and isotherm.

A magnetic hydrogel based on xylan (X), poly (acrylic acid), and maghemite (γ-Fe2O3) named HXA-Fe2O3 was synthesized, characterized, and applied as an alternative material to remove methylene blue (MB) from aqueous media by adsorption. Maghemite was synthesized by coprecipitation method and later incorporated in the hydrogel matrix synthesized by free radical polymerization. The characterization studies included FTIR, DSC, XRD, VSM, Zeta Potential, TGA, SEM, TEM, and N2 adsorption isotherms (BET). The physicochemical characterization results confirmed the intended synthesis and showed the compositional, thermal, structural, morphological, textural, and magnetic profile of the materials. The adsorption studies included experimental design, kinetic, and isotherm. A full factorial design was employed considering the factors adsorbent dosage (g L-1), pH, and ionic strength (mmol L-1 of NaCl) for adsorption capacity and removal percentage responses. As ionic strength was not significant, a Doehlert design was employed with adsorbent dosage and pH, indicating the optimal adsorption conditions. The kinetics was well described by the PSO model, while the isotherm obeyed the Sips model. Equilibrium was attained at 60 min, and the maximum experimental adsorption capacity was up to 250.26 mg g-1 at pH 8.5, adsorbent dosage of 0.2 g L-1, and 298 K. These findings show that the magnetic hydrogel produced has great potential to be applied in the adsorption of basic molecules, such as MB.

Development of hydrogels based on xylan and poly (acrylic acid) for melamine adsorption in batch and continuous mode: experimental design, kinetics, isotherms, recyclability, and fixed-bed column.

Two hydrogels were synthesized, characterized, and applied as alternative materials to remove melamine (MEL) from aqueous media by adsorption. For the first time, a complete study of MEL adsorption is presented, including optimization, kinetics, isotherm, reuse, and column studies with these new materials. One hydrogel is based on xylan and poly (acrylic acid) and was named HXy, and the other is based on the same components functionalized with activated carbon and was named HXy-AC. The materials were synthesized by free radical polymerization and characterized by FTIR, XRD, TGA, DSC, SEM, zeta potential, point of zero charge, N2 adsorption isotherms (BET), helium gas pycnometry, Archimedes method, swelling analysis, and stability tests. The characterization results confirmed the intended synthesis and showed the thermal, morphological, textural, structural, and compositional profile, as well as the adsorption characteristics of the materials. The adsorption studies in batch process included experimental design, kinetics, isotherms, and recyclability, and in continuous mode, the studies included fixed-bed column experiments. The full factorial design showed that adsorbent dosage, pH, and ionic strength are significant for adsorption capacity and removal percentage responses. Doehlert design enabled the definition of the values of adsorbent dosage and pH that were most suitable for MEL adsorption into the materials, indicating the optimal adsorption conditions. The kinetics were well described by the pseudo-first-order model, with R2 above 0.9920 for both materials at all concentrations tested. The isotherm obeyed the Langmuir model, with R2 above 0.9939 for both materials at all temperatures tested. Equilibrium was attained at 180 min, and the maximum experimental adsorption capacity was up to 132.46 and 118.96 mg g-1 at pH 7, with adsorbent dosage of 0.5 g L-1, and 298 K for HXy and HXy-AC, respectively. Furthermore, HXy and HXy-AC materials maintained about 58 and 70% of their initial adsorption capacity at the end of five adsorption/desorption cycles, respectively. Breakthrough curves were described by the Yan model and presented a maximum adsorption capacity of 30.2 and 30.4 mg g-1, treating 3.4 and 6.1 L of influent until the breakthrough point of 0.5 mg L-1 with HXy-AC using 2.0 and 4.0 g of material, respectively. These findings show that the hydrogels produced present the potential to be applied in the adsorption of basic molecules, such as MEL.

Drug-excipient compatibility studies in formulation development: A case study with benznidazole and monoglycerides.

Monoglycerides (MGs) such as glycerol monolaurate (GML) and glycerol monostearate (GMS) have been used as excipients in oral formulations because of their emulsifying effect as well as their ability to inhibit the precipitation and intestinal efflux of drugs. Excipient-drug compatibility studies, however, have been underexplored. In this study, benznidazole (BNZ) was selected as a drug model due to the difficulty in improving its solubility and because of the potential impact on public health (it is the only drug currently used to treat Chagas disease). The effect of different processing conditions (maceration, ball milling, and melting) on the physical-chemistry properties of BNZ/MGs mixtures was investigated to guide the rational development of new solid formulations. GML was more effective in improving the solubility of BNZ, which could be due to its more malleable structure, less hydrophobic nature, and greater interaction with BNZ. The formation of hydrogen bonds between the imidazole group of BNZ and the polar region of GML was confirmed by spectroscopy analyses (IR, 1H NMR). The higher the monoglyceride content in the mixture, the higher the BNZ solubility. Regardless of the method of processing the mixture, the drug was found to be crystalline. Polarized light microscopy analysis showed the presence of spherulites. Overall, these findings suggest that preparation methods of BNZ:MGs formulations that involve thermal or/and mechanical treatment have a low impact on the solid properties of the material, and this allows for the production of formulations with reproducible performance.

Immobilized acetylcholinesterase in magnetic nanoparticles for in-line inhibition studies using a capillary electrophoresis system.

Enzyme assays can be performed with the capillary electrophoresis technique (CE) in many approaches, such as the immobilized enzyme micro-reactor. Acetylcholinesterase is a promising enzyme to be used when pursuing such a method, as it has already been explored in the proposal of similar methods of miniaturizing enzyme assays. The present work proposes a novel enzyme micro-reactor, based on the anchorage of the enzyme on magnetic nanoparticles of MnFe2O4, with chitosan and glutaraldehyde as the cross-linker in the capillary by means of an arrange of neodymium magnets. The calculated Km of the enzyme evaluated by this method was 1.12 mmol L-1, comparable to other studies in the literature that utilizes immobilized enzymes. Also, IC50 for neostigmine was assessed in 3 different micro-reactors, with an average of 29.42 ± 3.88 µmol L-1. In terms of the micro-reactor stability, it was possible to perform at least 25 experiments with assembled micro-reactor. The method was applied to hydroalcoholic extracts of 7 plant species. Plinia cauliflora had the best result, with 42.31 ± 6.81% of enzyme inhibition in a concentration of 100 mg L-1.

Advanced Solid Formulations For Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is an opportunistic and endogenous infection caused by a fungus of the Candida genus, which can cause pruritus, dysuria, vulvar edema, fissures and maceration of the vulva. The treatment of vaginal candidiasis is carried out mainly by antifungal agents of azole and polyene classes; however, fungal resistance cases have been often observed. For this reason, new therapeutic agents such as essential oils, probiotics and antimicrobial peptides are being investigated, which can be combined with conventional drugs. Local administration of antimicrobials has also been considered to allow greater control of drug delivery and reduce or avoid undesirable systemic adverse effects. Conventional dosage forms such as creams and ointments result in reduced residence time in the mucosa and non-sustained and variable drug delivery. Therefore, advanced solid formulations such as intravaginal rings, vaginal films, sponges and nanofibers have been purposed. In these systems, polymers in different ratios are combined aiming to achieve a specific drug release profile and high mucoadhesion. Overall, a more porous matrix structure leads to a higher rate of drug release and mucoadhesion. The advantages, limitations and technological aspects of each dosage form are discussed in detail in this review.

Chitosan/genipin modified electrode for voltammetric determination of interleukin-6 as a biomarker of sepsis.

Ultrasensitive electroanalytical monitoring of interleukin-6 levels in serum samples has emerged as a valuable tool for the early diagnosis of inflammatory diseases. Despite its advantages, there is a lack of strategies for the label-free voltammetric determination of cytokines. Here, a novel chitosan/genipin modified fluorine tin oxide electrode was developed providing an in-situ hydrogel formation (FTO/CSG). This platform was applied for the detection of interleukin-6, a major pro-inflammatory cytokine. Transmission electron microscopy (TEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) indicated genipin serves as an efficient green cross-linker to build the immunosensing platform (FTO/CSG/anti-IL-6). EIS showed an increase in charge transfer resistance from 326 to 1360 kΩ after the immobilization of anti-IL-6 antibodies. By square wave voltammetry, this method achieved a detection limit of 0.03 pg mL-1 with a wide linear range of 0.05-1000 pg mL-1. Additionally, it displayed a high selectivity index when tested in the presence of three inflammatory cytokines as interfering proteins: IL-12, IL-1ß, and TNF-α. The sample matrix effect showed a peak current variation lower than 5 %. The novel method was applied for the quantification of IL-6 in serum samples of septic mice. No statistical differences were observed between the standard ELISA and the proposed method using a confidence level of 95 %.

Structure and interaction roles in the release profile of chalcone-loaded liposomes.

The structures and molecular interactions of established synthetic chalcones were correlated with their release profiles from asolectin liposomes. The effects of chalcones on the properties of liposomes were evaluated by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-VIS), horizontal attenuated total reflection Fourier transform infrared (HATR-FTIR), 31P nuclear magnetic resonance (31P NMR), zeta (ζ) potential and differential scanning calorimetry (DSC). The profiles and mechanisms of release were accessed according to the Korsmeyer-Peppas model. Results obtained allowed the establishment of a relationship between the chalcone release profile and 1) the ordering effects of chalcones in different membrane regions, 2) their polar or interfacial location in the lipid layer, 3) the influence of hydroxy and methoxy substituents, 4) their effect on reorientation of lipid choline-phosphate regions. The obtained data may improve the development of chalcone-based systems to be used in the therapy of chronic and acute diseases.

Development and characterization of thermopressed polyvinyl alcohol films for buccal delivery of benznidazole.

Given that oral preparations of benznidazole (BZN) have demonstrated limited efficacy in the treatment of Chagas' disease due to pharmacokinetic or toxicological problems, the development of buccal polymeric films was purposed in this study. These systems ensure high patient acceptability and direct access to the systemic circulation, improving drug bioavailability and toxicological profile. Polymer films were prepared through a thermopressing method by mixing BZN and polyvinyl alcohol (PVAL). In some preparations, propylene glycol (PG) and thymol (TM) were also included as plasticizer and chemical absorption enhancer, respectively. Morphology, X-ray diffraction, spectroscopic, thermal, mechanical, and water uptake properties, as well as ex vivo permeability studies, were performed to characterize the film formulations. BZN remained stable and in an amorphous form over 90 days. The addition of PG and TM improved the mechanical properties of the films, making them soft, flexible and tear-resistant. Also, these additives increased the water sorption rate of the films at 50 and 75% relative humidity and the TM increased the film erosion properties and drug permeability (close to 6×) compared to control. It was hypothesized that the permeability improvement of thymol-based films that follow a drug release profile through erosion is also associated with the inhibition of the crystallization of BNZ when the film is in contact with the buccal mucosa. Once the thymol has previously demonstrated a significant in vivo and in vitro trypanocidal action and even improved film characteristics, these systems may be considered promising for Chagas' disease treatment.

Sensitive simultaneous voltammetric determination of the herbicides diuron and isoproturon at a platinum/chitosan bio-based sensing platform.

Phenylurea herbicides are persistent contaminants, which leads their transport to the surface and ground waters, affecting human and aquatic organisms. Different analytical methods have been reported for the detection of phenylureas; however, several of them are expensive, time-consuming, and require complex pretreatment steps. Here, we show a simple method for the simultaneous electrochemical determination of two phenylurea herbicides by differential pulse adsorptive stripping voltammetry (DPAdSV) using a modified platinum/chitosan electrode. The one-step synthesized platinum/chitosan PtNPs/CS was successfully characterized by TEM, XRPD, and FT-IR, and applied through the sensing platform designated as PtNPs/CS/GCE. This bio-based modified electrode is proposed for the first time for the individual and/or simultaneous electrochemical detection of the phenylurea herbicides diuron and isoproturon compounds extensively used worldwide that present a very similar chemical structure. Electrochemical and interfacial characteristics of the modified electrode were evaluated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). It was found that the oxidation mechanism of diuron and isoproturon occurs in two different pathways, with a peak-to-peak definition of ca. 0.15 V. Under differential pulse adsorptive stripping voltammetry (DPAdSV) optimized conditions, the limit of detection (LOD) was estimated as 7 µg L-1 for isoproturon and 20 µg L-1 for diuron (Ed = +0.8 V; td = 100 s). The proposed method was successfully applied to the determination of both analytes in river water samples, at three different levels, with a recovery range of 90-110%. The employment of the bio-based sensing platform PtNPs/CS/GCE allows a novel and easy analytical method to the multi-component phenylurea herbicides detection.

Development of curcumin-loaded chitosan/pluronic membranes for wound healing applications.

The emergence of new materials with improved antibacterial, anti-inflammatory and healing properties compared to conventional wound dressings has both social and economic appeal. In this study, novel chitosan-based (CTS) membranes containing curcumin (CUR) incorporated in Pluronic (PLU) copolymers were developed and characterized to obtain suitable properties for applications as a wound healing dressing. The mechanical, thermal, swelling, wettability, release and permeation properties were evaluated by DSC, TGA, water contact angle measurements, FTIR, fluorescence and microscopic techniques. Membranes containing PLU and CUR presented wettability close to the ideal range for interaction with cellular components (contact angle ~40-70°), improved mechanical properties, higher thermal stability, high swelling degree (>800%) and CUR release (~60%) compared to samples without PLU addition. A higher retention of CUR in the epidermis than in the dermis layer was observed, which also was confirmed by confocal microscopy. Furthermore, the CTS-PLU membranes loaded with CUR showed to be active against Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 25 and 100 mg mL-1, respectively), the microbial species most present in chronic wounds. Overall, the CTS-PLU-CUR membranes presented suitable properties to act as a new wound healing dressing formulation and in vivo studies should be performed to confirm these benefits.

Understanding the interaction between Soluplus® and biorelevant media components.

Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) is a solubilizing copolymer commonly applied as carrier in solid dispersions of poorly soluble drugs. This polymer is used to increase the apparent solubility of drugs with low aqueous solubility and consequently enhance drug absorption by the human gastrointestinal tract. To select the appropriate carrier to compose solid dispersions, in vitro supersaturation studies were applied as a pre-formulation tool, using different dissolution media. During in vitro supersaturation studies performed for the poorly soluble drug candesartan cilexetil, it was found that Soluplus® may interact with components of the biorelevant medium Fasted State Simulated Intestinal Fluid, lowering the drug apparent solubility. Dynamic Light Scattering and Transmission Electron Microscopy analyses were performed, as well as fluorescence measurements, aiming to characterize the interaction behavior and determine the polarity of the microenvironment. It was evidenced that Soluplus® interacted preferentially with lecithin, forming mixed micelles with a more polar microenvironment, which lowered the candesartan cilexetil solubilization capacity and consequently reduced its apparent solubility in the biorelevant medium. These findings are important to emphasize the key role of the media selection for in vitro solubility-supersaturation studies, where media that could mimic the human gastrointestinal environment are recommended.

The role of the lecithin addition in the properties and cytotoxic activity of chitosan and chondroitin sulfate nanoparticles containing curcumin.

Surfactants have been used as a tool to improve the properties of polymeric nanoparticles (NPs) and to increase the rate of hydrophobic drug release by means of these nanoparticles. In this context, this study evaluated the effect of lecithin on the characteristics of chitosan (CHI) and chondroitin sulfate (CS) nanoparticles, when applied in curcumin (Curc) release. CHI/CS NPs and CHI/CS/Lecithin NPs were prepared by the ionic gelation method, both as standards and containing curcumin. Simultaneous conductimetric and potentiometric titrations were employed to optimize the interaction between the polymers. NPs with hydrodynamic diameter of ∼130 nm and zeta potential of +60 mV were obtained and characterized by HRTEM; their pore size and surface area were also analyzed by BET method, DLS, FTIR, XPS, and fluorescence spectroscopy techniques to assess morphological and surface properties, stability and interaction between polymers and to quantify the loading of drugs. The final characteristics of NPs were directly influenced by lecithin addition, exhibiting enhanced encapsulation efficiency of curcumin (131.8 µg curcumin per mg CHI/CS/Lecithin/Curc NPs). The release of curcumin occurred gradually through a two-stage process: diffusion-controlled dissolution and release of curcumin controlled by dissolution of the polymer. However, the release of curcumin in buffer solution at pH 7.4 was achieved faster in CHI/CS/Lecithin/Curc NPs than in CHI/CS/Curc NPs. in vitro cytotoxic activity evaluation of the curcumin was determined by the MTT assay, observing that free curcumin and curcumin nanoencapsulated in CHI/CS/Curc and CHI/CS/Lecithin/Curc NPs reduced the viability of MCF-7 cells in the 72 h period (by 28.4, 36.0 and 30.7%, P < 0.0001, respectively). These results indicate that CHI/CS/Lecithin NPs have more appropriate characteristics for encapsulation of curcumin.

Dimiristoylphosphatidylcholine/genistein molecular interactions: A physico-chemical approach to anti-glioma drug delivery systems.

Regarding free genistein small delivery to the central nervous system, physico-chemical parameters of dimiristoylphosphatidylcholine liposome-loaded genistein were investigated, as well as its in vitro activity against the DPPH radical and glioma cells. Data obtained by UV-vis spectroscopy, Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, Differential Scanning Calorimetry and Dynamic Light Scattering were used to characterize the liposomal system with respect to motion restriction, hydration degree, trans-gauche isomerization and phase state. In vitro antitumoral effects were monitored through conting and viability assays. Genistein hydroxyl group and lipid hydrogen bonds may have important role in dimiristoylphosphatidylcholine phosphate and choline motion restriction. Genistein-induced choline restriction may be also related to a decrease in the group rotation rate. Genistein: dimiristoylphosphatidylcholine system showed higher molecular package at the acyl chains region compaired to empty liposomes, and it may be related to a decrease in gauche bonds quantity and system size. Lipid acyl chain length seems to influence different genistein effects on membranes, due to the presence of gauche conformers. Genistein: dimiristoylphosphatidylcholine liposome was more efficient as DPPH reducting system than the free-Gen. Liposomal system, at genistein 100 µM, was so efficient as the correspondent free-form genistein, probably showing higher stability to cross the blood-brain barrier. Genistein and the lipid did not show an additive activity against glioma cells. Antioxidant and anti-glioma genistein-loaded liposome potential may be related to the isoflavone location and its restriction effect in the lipid molecular motion. Anti-glioma activity may also be related to a decrease of system size and trans-gauche isomerization.

A new and efficient carboxymethyl-hexanoyl chitosan/dodecyl sulfate nanocarrier for a pyrazoline with antileukemic activity.

We describe herein a chitosan nanocarrier for drug delivery applications obtained through the self-assembly of carboxymethyl-hexanoyl chitosan and dodecyl sulfate (CHC-SDS). Nanocapsules with spherical morphology were obtained in phosphate buffer at pH 7.4. These CHC-SDS nanocapsules showed no toxicity toward Jurkat cells (acute lymphoblastic leukemia) and were used to encapsulate a new pyrazoline (H3TM04) with antileukemia activity. The samples were characterized by dynamic light scattering (DLS) and Laser Doppler Micro-Electrophoresis. The encapsulation efficiency was higher than 96% (293.6 µg mL-1) and the H3TM04-loaded nanocapsules (CHC-SDS-H) had a negative surface charge (-29.8 ±â€¯0.7 mV) and hydrodynamic radius of around 84 nm. For the first time, CHC-SDS-H were formed and the antitumoral cancer activity was proved. The in vitro assays showed the controlled release of H3TM04 from the CHC-SDS-H nanocapsules in phosphate buffer pH 7.4. The H3TM04 release data were described by the power law model, indicating that H3TM04 delivery occurred via an erosion mechanism. The cytotoxicity assays with Jurkat and K-562 cells (acute myeloid leukemia) demonstrated that the CHC-SDS-H nanocapsule decreases the half maximal inhibitory concentration (IC50). The study showed that CHC-SDS nanocapsules represent a promising nanocarrier for pyrazoline derivates that could be applied in leukemia therapy.

Temperature Evaluation of Curcumin Keto-Enolic Kinetics and Its Interaction with Two Pluronic Copolymers.

Curcumin (CUR), a natural hydrophobic polyphenol isolated from Curcuma longa, has been reported to possess two main equilibria in aqueous solutions, diketo/keto-enolic tautomerism and self-aggregation. The thermodynamics of tautomeric equilibrium is well established; however, its kinetic parameters have been sparsely studied. Various efforts have been made to improve CUR solubility in aqueous media. We evaluated how the kinetics of tautomerism and the interaction of CUR with pluronic P123 and F127 copolymers in solution were affected by temperature, using UV-vis and fluorescence spectroscopies. Pluronic particle sizes with and without CUR were acquired by dynamic light scattering. The interaction in the solid state was verified by differential scanning calorimetry (DSC). The equilibrium rate that displaces to the diketo form increased fivefold when the temperature rose from 294 to 314 K with an activation energy of 61.2 kJ mol-1. The CUR solubility increased from 2.58 to 6.77 mg g-1 when incorporated in P123 and from 0.05 to 3.54 mg g-1 when incorporated in F127 with a change in the temperature from 298 to 314 K. This process had a Gibbs free energy of around -1 and -13 kJ mol-1 because of CUR solubilization into the inner core of pluronic micelles. Particle sizes of about 11 nm were obtained for both copolymers containing CUR in an aqueous solution above the critical micelle temperature. DSC measurements showed melting point depression of both CUR and F127. P123 presented no significant variation in the melting point because of its low melting enthalpy. The results indicate that temperature significantly influences CUR kinetic tautomerism and its interaction with both P123 and F127 copolymers. P123 presents a higher interaction in aqueous solution with CUR than F127. Both pluronics could contribute to a safer and more efficient CUR administration in the bloodstream.

Molecular interactions and physico-chemical characterization of quercetin-loaded magnetoliposomes.

The bioflavonoid quercetin may prevent magnetoliposomes oxidation, preserving their stability. In this work, the interaction between quercetin and asolectin-based magnetoliposomes was investigated by monitoring the hydration degree, vibrational, rotational and translational mobility parameters of the system as well as its thermodynamic properties. The efficiency of the encapsulation of maghemite magnetic nanoparticles was detected by high resolution-continuum source flame atomic absorption spectrometry (HR-CS FAAS). The magnetic behavior of the system was studied by vibrating sample magnetometry (VSM) technique. The size and surface charge of magnetoliposomes were detected by dynamic light scattering (DLS) and zeta potential (ζ-potential) measurements. The influence of quercetin on the physico-chemical parameters of the magnetoliposomes was evaluated by Fourier transform infrared spectroscopy (FTIR), 31P and 1H nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. In vitro antioxidant and antitumoral assays were also performed for the magnetoliposomes. An insertion of quercetin into magnetoliposomes reduced the efficiency of the encapsulation of maghemite nanoparticles by 11%, suggesting a significant interaction between flavonoid and nanoparticles in a specific region of the system. Quercetin discreetly decreased the saturation magnetization of magnetoliposomes, but did not affect the superparamagnetic behavior of the system. 31P and 1H NMR results showed that quercetin did not alter the inverted hexagonal system phase state but decreased lipid polar head mobility. The flavonoid also seems to reorient the choline group above the bilayer phosphate membrane plane, as indicated by ζ-potential system values. FTIR, NMR and DSC responses showed that quercetin disordered the carbonyl and the methylene regions of the magnetoliposomes. Quercetin, as the nanoparticles, seems to be located in the polar head regions of magnetoliposomes, ordering it and diminishing the lipid intermolecular communication in the membrane carbonyl and non-polar regions. The lipid peroxidation of the magnetoliposomes was prevented 8-fold by the presence of quercetin in the system. Also, the flavonoid was responsible for a 45% reduction in the viability of glioma cells. Location and interactions between quercetin and magnetoliposomes components were discussed in order to be correlated with the results of biological activity, contributing to the design of more stable and efficient magnetoliposomes to be applied as contrast and antitumoral agents.

Novel magneto-responsive nanoplatforms based on MnFe2O4 nanoparticles layer-by-layer functionalized with chitosan and sodium alginate for magnetic controlled release of curcumin.

Remotely assisted drug delivery by means of magnetic biopolymeric nanoplatforms has been utilized as an important tool to improve the delivery/release of hydrophobic drugs and to address their low cargo capacity. In this work, MnFe2O4 magnetic nanoparticles (MNPs) were synthesized by thermal decomposition, coated with citrate and then functionalized with the layer-by-layer (LbL) assembly of polyelectrolyte multilayers, with chitosan as polycation and sodium alginate as polyanion. Simultaneous conductimetric and potentiometric titrations were employed to optimize the LbL deposition and to enhance the loading capacity of nanoplatforms for curcumin, a hydrophobic drug used in cancer treatment. ~200 nm sized biopolymer platforms with ~12 nm homogeneously embedded MNPs were obtained and characterized by means of XRD, HRTEM, DLS, TGA, FTIR, XPS and fluorescence spectroscopy techniques to access structural, morphological and surface properties, to probe biopolymer functionalization and to quantify drug-loading. Charge reversals (±30 mV) after each deposition confirmed polyelectrolyte adsorption and a stable LbL assembly. Magnetic interparticle interaction was reduced in the biopolymeric structure, hinting at an optimized performance in magnetic hyperthermia for magneto-assisted drug release applications. Curcumin was encapsulated, resulting in an enhanced payload (~100 µg/mg). Nanocytotoxicity assays showed that the biopolymer capping enhanced the biocompatibility of nanoplatforms, maintaining entrapped curcumin. Our results indicate the potential of synthesized nanoplatforms as an alternative way of remotely delivering/releasing curcumin for medical purposes, upon application of an alternating magnetic field, demonstrating improved efficiency and reduced toxicity.

Physico-chemical characterization of asolectin-genistein liposomal system: An approach to analyze its in vitro antioxidant potential and effect in glioma cells viability.

In this study, the interaction between soy isoflavone genistein and asolectin liposomes was investigated by monitoring the effects of isoflavone on lipidic hydration, mobility, location and order. These properties were analyzed by the following techniques: horizontal attenuated total reflection Fourier transform infrared spectroscopy (HATR-FTIR), low-field (1)H nuclear magnetic resonance (NMR), high-field (31)P NMR, zeta potential, differential scanning calorimetry (DSC) and UV-vis spectroscopy. The antioxidant and antitumoral activities of the genistein liposomal system were also studied. The genistein saturation concentration in ASO liposomes corresponded to 484 µM. HATR-FTIR results indicated that genistein influences the dynamics of the lipidic phosphate, choline, carbonyl and acyl chain methylenes groups. At the lipid polar head, HATR-FTIR and (31)P NMR results showed that the isoflavone reduces the hydration degree of the phosphate group, as well as its mobility. Genistein ordered the lipid interfacial carbonyl group, as evidenced by the HATR-FTIR bandwidth analysis. This ordering effect was also observed in the lipidic hydrophobic region, by HATR-FTIR, NMR, DSC and turbidity responses. At the saturation concentration, liposome-loaded genistein inhibits the lipid peroxidation induced by hydroxyl radical in 90.9%. ASO liposome-loaded genistein at 100 µM decreased C6 glioma cell viability by 57% after 72 h of treatment. Results showed an increase of the genistein in vitro activities after its incorporation in liposomes. The data described in this work will contribute to a better understanding of the interaction between genistein and a natural-source membrane and of its influence on isoflavone biological activities. Furthermore, the antitumoral results showed that genistein-based liposomes, which contain natural-sourced lipids, may be promising as a drug delivery system to be used in the glioma therapy.

Physico-chemical characterization and cytotoxicity evaluation of curcumin loaded in chitosan/chondroitin sulfate nanoparticles.

In this study, chitosan (CTS)/chondroitin sulfate (CS) nanoparticles, both pure and curcumin-loaded, were synthesized by ionic gelation. This method is simple and efficient for obtaining nanoparticles with a low polydispersity index (0.151±0.03 to 0.563±0.07) and hydrodynamic diameter in the range of 175.7±2.5 to 710.2±8.9nm, for this study. Samples have a relatively high zeta potential value, a fact that indicates that the colloidal system has good physical and chemical stabilities. The efficiency of the curcumin encapsulation in nanoparticles, which ranged from 62.4±0.61% to 68.3±0.88%, depends on the pH of the chitosan solution. The release of curcumin from the nanoparticles was enabled by a diffusion mechanism, with fast release in a phosphate buffer solution at pH6.8. The assaying of cell viability by the MTT test showed that the presence of both free curcumin and curcumin in the nanoencapsulated form leads to a statistically significant reduction in the viability of A549 cells, by comparison with the control group. The most significant reductions in cell viability of 41.1% and 60.4% (p<0.0001) were observed after 72h, by using 40µmol∙L(-1) free curcumin and curcumin encapsulated in CTS/CS nanoparticles with the chitosan solution at pH6.0, respectively.

Development and evaluation of pH-sensitive sodium alginate/chitosan microparticles containing the antituberculosis drug rifampicin.

This paper describes the encapsulation of a high molecular weight molecule rifampicin (RIF) in sodium alginate/chitosan microparticles, which provided controlled-release when evaluated in vitro. The microparticles were prepared by the coacervation technique. To evaluate and select the best encapsulation method two approaches were applied: coacervation (MCP method 1) and impregnation (MCP method 2). The microparticles obtained were analyzed by DSC, DRIFT, XRD and SEM and also the loading efficiency, swelling degree (SD) and in vitro release were determined. The results obtained showed that the alginate/chitosan microparticles represent an efficient system for the controlled-release of RIF. At acidic pH, the release of 20% of the drug occurred in 2h, and at pH6.8 a rapid increase in the release rate was observed up to 100%. The mechanism involved in the release was Super Case II kinetics since n>1 (n=1.09 and 1.13 for microparticles produced by methods 1 and 2, respectively), indicating that the release was related to diffusion, swelling, relaxation and erosion processes. The dissolution efficiencies were similar for both formulations, and the f2 values of ≥50 indicated the similarity between the two profiles, under the assumption of a maximum allowable difference of 10%.