Simultaneous Formation of Polyhydroxyurethanes and Multicomponent Semi-IPN Hydrogels.

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. Monomer E-based PHU exhibited higher Mw¯ than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

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.

In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations.

The extensive use of oral dosage forms for the treatment of diseases may be linked to deficient pharmacokinetic properties. In some cases the drug is barely soluble; in others, the rapid transit of the formulation through the gastrointestinal tract (GIT) makes it difficult to achieve therapeutic levels in the organism; moreover, some drugs must act locally due to a gastric pathology, but the time they remain in the stomach is short. The use of formulations capable of improving all these parameters, as well as increasing the resident time in the stomach, has been the target of numerous research works, with low-density systems being the most promising and widely explored, however, there is further scope to improve these systems. There are a vast variety of polymeric materials used in low-density gastroretentive systems and a number of methods to improve the bioavailability of the drugs. This works aims to expedite the development of breakthrough approaches by providing an in-depth understanding of the polymeric materials currently used, both natural and synthetic, their properties, advantages, and drawbacks.

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.

Validation of Smart Nanoparticles as Controlled Drug Delivery Systems: Loading and pH-Dependent Release of Pilocarpine.

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%-DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.

Reversible pH-Sensitive Chitosan-Based Hydrogels. Influence of Dispersion Composition on Rheological Properties and Sustained Drug Delivery.

The present work deals with the synthesis of micro-structured biomaterials based on chitosan (CTS) for their applications as biocompatible carriers of drugs and bioactive compounds. Twelve dispersions were prepared by means of functional cross-linking with tricarballylic acid (TCA); they were characterized by Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MTDSC) and scanning electron microscopy (SEM), and their rheological properties were studied. To the best of the authors' knowledge, no study has been carried out on the influence of CTS concentration, degree of cross-linking and drug loading on chitosan hydrogels for drug delivery systems (DDS) and is investigated herein for the first time. The influence of dispersion composition (polymer concentration and degree of cross-linking) revealed to exert a marked impact on its rheological properties, going from liquid-like to viscoelastic gels. The release profiles of a model drug, diclofenac sodium (DCNa), as well as their relationships with polymer concentration, drug loading and degree of cross-linking were evaluated. Similar to the findings on rheological properties, a wide range of release profiles was encountered. These formulations were found to display a well-controlled drug release strongly dependent on the formulation composition. Cumulative drug release under physiological conditions for 96 h ranged from 8% to 67%. For comparative purpose, Voltaren emulgel® from Novartis Pharmaceuticals was also investigated and the latter was the formulation with the highest cumulative drug release (85%). Some formulations showed similar spreadability values to the commercial hydrogel. The comparative study of three batches confirmed the reproducibility of the method, leading to systems particularly suitable for their use as drug carriers.

Recovery of Zn from acid mine water and electric arc furnace dust in an integrated process.

In this paper, the purification of acid mine water and the treatment of electric arc furnace dust (EAFD) are integrated into one process with the aim of recovering the Zn content of both effluent and waste. Zinc recovery can reduce the cost of their environmental management: purified acid mine water is discharged after removing all metals; EAFD ceases to be hazardous waste; and Zn is valorised. The process consists of the recovery of Zn as zinc oxide and its purification into commercial products. First, EAFD is leached with acid water and the dissolved metals are selectively precipitated as hydroxides. After EADF leaching, ferrous iron is bio-oxidized and Fe and Al are then precipitated; in the following stage, Cu, Ni, Co and Cd are cemented and finally Zn is precipitated as ZnO. In order to purify water that finally is discharged to a river, lime is used as the neutralizing agent, which results in a precipitate of mainly gypsum, MnO, and ZnO. From the impure zinc oxide produced, various alternatives for the attainment of commercial products, such as basic zinc carbonate and electrolytic zinc, are studied in this work.