Biodegradable double cross-linked chitosan hydrogels for drug delivery: Impact of chemistry on rheological and pharmacological performance.

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.

Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release.

In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box⁻Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79⁻81%), and the CTS-NPs composites (29⁻34%).

Loading studies of the anticancer drug camptothecin into dual stimuli-sensitive nanoparticles. Stability scrutiny.

In recent years, the preparation of valuable drug delivery systems (DDS) from self-assembled amphiphilic copolymers has attracted much attention since these nanomaterials provide new opportunities to solve problems such as the lack of solubility in water of lipophilic drugs, improve their bioavailability, prolong their circulation time and decrease the side effects associated with their administration. In the current study two types of biocompatible pH-responsive nanoparticles derived from poly(2-hydroxyethyl methacrylate) (pHEMA) have been used as drug nano-carriers, being one of them core cross-linked to circumvent their instability upon dilution in human fluids. The present paper deals with the optimization of the loading process of the labile, hydrophobic and highly active anticancer drug, Camptothecin (CPT) into the nanoparticles with regard to four independent variables: CPT/polymer ratio, sonication, temperature and loading time. Forty experiments were carried out and a Box-Behnken experimental design was used to evaluate the significance of the independent variables related to encapsulation efficiency and drug retention capacity. The enhanced drug loading and encapsulation efficiency values (58% and >92%, respectively) of CPT were achieved by the core cross-linked NPs in 2 h at 32 °C at CPT/polymer ratio 1.5:1 w/w and 14 min of sonication. The optimized CPT-loaded NPs were studied by dynamic light scattering and scanning electron microscopy, and an increase in size of the loaded-NP compared to the unloaded counterparts was found. Other twenty experiments were conducted to study the enability to retain CPT into the conjugates at different ionic strength values and times. The stability studies demonstrated that the core cross-linked nanocarriers displayed an excellent drug retention capacity (>90%) at 25 °C for 15 days in every ionic-strength environments whereas the non-cross-linked ones were more stable at physiological ionic strength. The optimized systems proved to be a major step forward to encapsulate and retain CPT in the NP nuclei, what makes them ideal devices to control the delivery of CPT upon the triggered acidic conditions of solid tumors.

Evaluation of heavy metals and arsenic speciation discharged by the industrial activity on the Tinto-Odiel estuary, SW Spain.

This study reports the annual amount of heavy metals discharged by industrial activity into the estuary of the Ría of Huelva (SW Spain). The findings showed that the discharged metals found in highest amounts were Fe (11 t y⁻¹), Zn (3.4 t y⁻¹) and Mo (0.88 t y⁻¹). There were other metals with high pollutant charge, such as Ti (232 kg y⁻¹), As (228 kg y⁻¹), Ni (195 kg y⁻¹), Pb (100 kg y⁻¹), Cr (39 kg y⁻¹) and Cd (33 kg y⁻¹). These results were compared with pollutants transported via the Tinto and Odiel rivers from abandoned mining activities in the Iberian Pyrite Belt (IPB), and it was deduced that the amounts spilled exclusively by industries were less than 1% in relation to the total discharge. Hence, the treatment of residues from the IPB should be the priority goal to improve water quality in the estuary.

Effect of the previous composting on volatiles production during biomass pyrolysis.

Composting is a biological process of decomposition of organic materials in an aerobic environment, which modifies the chemical composition and the thermal behavior of biomass. During composting, fungi and bacteria promote the decomposition of hemicellulosic and cellulosic fractions, increasing the lignin proportion. Its product, compost, is usually used as an amendment to soil; however, its physicochemical characteristics turn it into an interesting feedstock in pyrolysis or gasification facilities. The changes that composting produces on biomass pyrolysis can be explained using an autocatalytic kinetic model (Prout-Tompkins). Thus, by means of a similar set of kinetic parameters for both the biomass and compost, it is possible to simulate the thermogravimetric analysis data (TG and DTG curves) of the materials as a sum of thermal degradations of its main pseudocomponents, hemicellulose, cellulose, lignin, and extractives. TG analysis coupled to mass spectrometry (MS) allows monitoring of the gas production during pyrolysis. Water and carbon oxide MS profiles can be simulated by an optimized linear combination of previously calculated DTG curves of pseudocomponents; however, in order to simulate the hydrogen MS signal, it is necessary to consider the char obtained in the course of the volatilization process. During pyrolysis, hydrogen production has two origins, volatilization of biomass pseudocomponents and charring. The last mechanism explains approximately 75% of the hydrogen obtained from compost. The pseudocomponent that produces more hydrogen by weight unit is lignin, showing a specific hydrogen production much higher than carbohydrates (3:1:8 for hemicellulose/cellulose/lignin). This fact, together with the greater lignin content in compost, explains the positive effect of composting on hydrogen production.