Ana C. S. Alcântara

Bionanocomposites based on alginate–zein/layered double hydroxide materials as drug delivery systems

The present work introduces new hybrid materials based on the combination of layered double hydroxides (LDH) and two biopolymers (a protein and a polysaccharide) to produce LDH–biopolymer nanocomposites, able to act as effective drug delivery systems (DDS) in comparison to the LDH or the biopolymers alone. Ibuprofen (IBU) has been chosen as a model drug, being intercalated in a Mg–Al LDH matrix. The resulting hybrid is used to prepare bionanocomposite materials by association with two biopolymers: (i) zein, a highly hydrophobic protein, and (ii) alginate, a polysaccharide widely applied for encapsulating drugs. Characterization of the IBU/Mg–Al LDH intercalation compound and the bionanocomposites resulting from its incorporation into alginate–zein matrices of different composition was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Preliminary kinetic studies of IBU liberation from bionanocomposites processed as beads show a better protection against drug release at the stomach pH and a controlled liberation in the intestinal tract conditions. This effect can be attributed to the hydrophobic nature of zein, which limits the passage of water and swelling of biocomposite beads prepared with such systems, delaying the release of the drug.

Pectin-coated chitosan-LDH bionanocomposite beads as potential systems for colon-targeted drug delivery.

This work introduces results on a new drug delivery system (DDS) based on the use of chitosan/layered double hydroxide (LDH) biohybrid beads coated with pectin for controlled release in the treatment of colon diseases. Thus, the 5-aminosalicylic acid (5ASA), the most used non-steroid-anti-inflammatory drug (NSAID) in the treatment of ulcerative colitis and Crohns disease, was chosen as model drug aiming to a controlled and selective delivery in the colon. The pure 5ASA drug and the hybrid material prepared by intercalation in a layered double hydroxide of Mg2Al using the co-precipitation method, were incorporated in a chitosan matrix in order to profit from its mucoadhesiveness. These compounds processed as beads were further treated with the polysaccharide pectin to create a protective coating that ensures the stability of both chitosan and layered double hydroxide at the acid pH of the gastric fluid. The resulting composite beads presenting the pectin coating are stable to water swelling and procure a controlled release of the drug along their passage through the simulated gastrointestinal tract in in vitro experiments, due to their resistance to pH changes. Based on these results, the pectin@chitosan/LDH-5ASA bionanocomposite beads could be proposed as promising candidates for the colon-targeted delivery of 5ASA, with the aim of acting only in the focus of the disease and minimizing side effects.

Clay-bionanocomposites with sacran megamolecules for the selective uptake of neodymium

Sacran, an anionic megamolecular polysaccharide extracted from the cyanobacterium Aphanothece sacrum, is an interesting biopolymer for developing functional clay-based bionanocomposites due to its colloidal and metal complexing properties. This work introduces novel bionanocomposites based on the assembly of sacran to sepiolite, a fibrous hydrated magnesium silicate, reporting some of their special features. Sacran–sepiolite films show tensile moduli about twice that of neat sacran films, and improved resistance and integrity in aqueous solutions. These materials can act as adsorbents of lanthanide ions, profiting from the well-known adsorption properties of sepiolite and the ability of sacran to complex rare earth and heavy metal ions. Sacran–sepiolite materials show a clear preference for Nd3+ ions over Ce3+, Eu3+ and Gd3+, and the results confirm the influence of the conformation of sacran chains in crystalline domains on the adsorption properties. In fact, only those materials prepared from concentrated sacran solutions, with the polysaccharide chains arranged as liquid crystals, and involving around 27% (w/w) of sepiolite showed a remarkable synergistic effect on the retention of Nd3+ ions, being promising as biosorbents for the effective and selective recovery of neodymium from aqueous media.

Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays.

Effective intercalation of zein into Na-montmorillonite: role of the protein components and use of the developed biointerfaces

Biohybrid materials based on the intercalation of zein, the major storage protein in corn, into sodium-exchanged montmorillonite were prepared following two synthesis strategies. The first one made use of zein dissolved in 80% (v/v) ethanol/water solution, the usual solvent for this protein, while the second method is new and uses a sequential process that implies the previous separation of zein components in absolute ethanol. This treatment of zein with ethanol renders a soluble yellow phase and an agglomerate of insoluble components, which are able to intercalate the layered silicate when an aqueous dispersion of montmorillonite is added to the ethanol medium containing both phases. The diverse steps in this second route were investigated individually in order to understand the underlying mechanism that drives to the intercalation of this complex hydrophobic biomacromolecule into the hydrophilic interlayer space of sodium-exchanged montmorillonite. In addition to physicochemical characterization of the resulting materials, these biohybrid interfaces were also evaluated as biofillers in the preparation of diverse ecofriendly nanocomposites.

Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS) have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

Bionanocomposites based on layered double hydroxides as drug delivery systems

The present work introduces new biohybrid materials involving layered double hydroxides (LDH) and biopolymers to produce bionanocomposites, able to act as effective drug delivery systems (DDS). Ibuprofen (IBU) and 5-aminosalicylic acid (5-ASA) have been chosen as model drugs, being intercalated in a Mg–Al LDH matrix. On the one side, the LDHIBU intercalation compound prepared by ion-exchange reaction was blended with the biopolymers zein, a highly hydrophobic protein, and alginate, a polysaccharide widely applied for encapsulating drugs. On the other side, the LDH- 5-ASA intercalation compound prepared by co-precipitation was assembled to the polysaccharides chitosan and pectin, which show mucoadhesive properties and resistance to acid pH values, respectively. Characterization of the intercalation compounds and the resulting bionanocomposites was carried out by means of different experimental techniques: X-ray diffraction, infrared spectroscopy, chemical and thermal analysis, as well as optical and scanning electron microscopies. Data on the swelling behavior and drug release under different pH conditions are also reported.

CHAPTER 1:Functional Nanocomposites Based on Fibrous Clays

This chapter is focused on functional nanocomposites based on the use of the microfibrous clays sepiolite and palygorskite as efficient fillers for diverse types of polymer matrices, from typical thermoplastics to biopolymers. The main features that govern the interaction between the silicates and the polymer matrix are discussed. The introduction addresses the structural and textural features of the fibrous silicates, as well as the possible synthetic approaches to increase the compatibility of these nanofillers with the polymeric matrix. Additionally, these clays can be easily functionalized through their surface silanol groups based on chemical reactions or by anchoring of nanoparticles. This allows for the preparation of a wide variety of functional polymer–clay nanocomposites. Thereafter, some relevant examples of nanocomposites derived from conventional polymers are reported, as well as of those based on polymers that exhibit electrical conductivity. Lastly, selected works employing sepiolite or palygorskite as fillers in polymeric matrixes of natural origin are discussed, showing the wide application of these resulting nanocomposites as bioplastics, as well as in biomedicine, environmental remediation and the development of sensor devices.