Preparation and characterization of porous membranes of glucomannan and silver decorated cellulose nanocrystals for application as biomaterial.

Bacterial infection usually represents a threat in medical wound care, due to the increase in treatment complexity and the risk of antibiotic resistance. For presenting interesting characteristics for the use as biomaterial, natural polymers have been explored for this application. Among them, a promising candidate is the konjac glucomannan (KGM) with outstanding biocompatibility and biodegradability but lack of antibacterial activity. In this study, KGM was combined with silver decorated cellulose nanocrystals (CNC-Ag) to prepare membranes by using a recent reported casting-freezing method. The results highlight the potential anti-adhesive activity of the new materials against Staphylococcus aureus upon contact, without the burst release of silver nanoparticles. Furthermore, the incorporation of CNC enhanced the thermal stability of these membranes while preserving the favorable mechanical properties of the KGM-based material. These findings highlight a straightforward approach to enhance the antibacterial properties of natural polymers, which can be effectively useful in medical devices like wound dressings that typically lack such properties.

Role of Alginate Composition on Copper Ion Uptake in the Presence of Histidine or Beta-Amyloid.

The anomalous interaction between metal ions and the peptide beta-amyloid is one of the hallmarks of Alzheimer's disease. Metal-binding biopolymers, including polysaccharides, can elucidate the fundamental aspects of metal ions' interactions with biological tissue and their interplay in Alzheimer's disease. This work focuses on the role of the alginate composition on Cu(II) adsorption in the presence of histidine or ß-amyloid, the peptide associated with the progression of Alzheimer's disease. Alginate samples with different mannuronic/guluronic (M/G) ratios led to similar Cu(II) adsorption capacities, following the Langmuir isotherm and the pseudo-second-order adsorption kinetic models. Although the presence of histidine produced up to a 20% reduction in the copper adsorption capacity in guluronic-rich alginate samples (M/G~0.61), they presented stable bidentate chelation of the metallic ion. Chemical analyses (FTIR and XPS) demonstrated the role of hydroxyl and carboxyl groups in copper ion chelation, whereas both crystallinity and morphology analyses indicated the prevalence of histidine interaction with guluronic-rich alginate. Similar results were observed for Cu(II) adsorption in alginate beads in the presence of beta-amyloid and histidine, suggesting that the alginate/histidine system is a simple yet representative model to probe the application of biopolymers to metal ion uptake in the presence of biological competitors.

Microfluidic encapsulation of nanoparticles in alginate microgels gelled via competitive ligand exchange crosslinking.

Efficient delivery of nanometric vectors complexed with nanoparticles at a target tissue without spreading to other tissues is one of the main challenges in gene therapy. One means to overcome this problem is to confine such vectors within microgels that can be placed in a target tissue to be released slowly and locally. Herein, a conventional optical microscope coupled to a common smartphone was employed to monitor the microfluidic production of monodisperse alginate microgels containing nanoparticles as a model for the encapsulation of vectors. Alginate microgels (1.2%) exhibited an average diameter of 125 ± 3 µm, which decreased to 106 ± 5 µm after encapsulating 30 nm fluorescent nanoparticles. The encapsulation efficiency was 70.9 ± 18.9%. In a 0.1 M NaCl solution, 55 ± 5% and 92 ± 4.7% of nanoparticles were released in 30 minutes and 48 hours, respectively. Microgel topography assessment by atomic force microscopy revealed that incorporation of nanoparticles into the alginate matrix changes the scaffold's interfacial morphology and induces crystallization with the appearance of oriented domains. The high encapsulation rate of nanoparticles, alongside their continuous release of nanoparticles over time, makes these microgels and the production unit a valuable system for vector encapsulation for gene therapy research.

Bulk and Microfluidic Synthesis of Stealth and Cationic Liposomes for Gene Delivery Applications.

This chapter describes the synthesis of stealth and cationic liposomes and their complexation with plasmid DNA to generate lipoplexes for gene delivery applications. Two techniques are presented: a top-down approach which requires a second step of processing for downsizing the liposomes (i.e., ethanol injection method) and a microfluidic technique that explores the diffusion of ethanol in water to allow the proper lipid self-assembly. The synthesis of stealth liposomes is also a challenge since the use of poly(ethylene glycol) favors the formation of oblate micelles. In this protocol, the stealth cationic liposome synthesis by exploring the high ionic strength to overcome the formation of secondary structures like micelles is described. Finally, the electrostatic complexation between cationic liposomes and DNA is described, indicating important aspects that guarantee the formation of uniform lipoplexes.

Hybrid microgels produced via droplet microfluidics for sustainable delivery of hydrophobic and hydrophilic model nanocarriers.

Drug delivery for treatment of chronic diseases relies on the effective delivery of payload materials into the target cells in a long-term release. In this context, the present study investigated hybrid microgels as platforms to carry nanoparticles to drug delivery. Hybrid microgels were produced with silk fibroin (SF) and chondroitin sulfate (CS), and alginate (ALG) by droplet microfluidics. ALG/SF, ALG/CS, and ALG/CS/SF microgels, ranging from 70-90 µm, were tested to encapsulate two model nanoparticles, polystyrene latex beads in pristine form (NPs) and NPs coated with bovine serum albumin (NPs-BSA) to simulate hydrophobic and hydrophilic nanocarriers, respectively. IR spectroscopy and fluorescence microscopy analysis confirmed the presence of SF and CS within ALG-based microgels revealing marked differences in their morphology and physicochemical properties. The release profiles of model nanoparticles revealed to be dependent on microgels composition and physicochemical properties. These findings show that SF ternary hybrid microgels facilitated the entrapment of hydrophobic nanocarriers with encapsulation efficiency (EE) from 83 to 98% keeping a better sustainable profile release than nonhybrid ALG microgels. Besides, CS improved the carriage of NPs-BSA (EE = 85%) and their profile release. The results highlight the versatility and tunable properties of these biobased microgels, being a good strategy to be used as an efficient platform in using macro and nanoencapsulated systems for drug delivery.

Coated electrospun bioactive wound dressings: Mechanical properties and ability to control lesion microenvironment.

Advanced wound dressings capable of interacting with lesions and changing the wound microenvironment to improve healing are promising to increase the therapeutic efficacy of this class of biomaterials. Aiming at the production of bioactive wound dressings with the ability to control the wound microenvironment, biomaterials of three different chemical compositions, but with the same architecture, were produced and compared. Electrospinning was employed to build up a biomimetic extracellular matrix (ECM) layer consisting of poly(caprolactone) (PCL), 50/50 dl-lactide/glycolide copolymer (PDLG) and poly(l-lactide) (PLLA). As a post-treatment to broaden the bioactivity of the dressings, an alginate coating was applied to sheathe and functionalize the surface of the hydrophobic electrospun wound dressings, in combination with the extract of the plant Arrabidaea chica Verlot, known for its anti-inflammatory and healing promotion properties. Wettable bioactive structures capable to interact with media simulating lesion microenvironments, with tensile strength and elongation at break ranging respectively from 155 to 273 MPa and from 0.94 to 1.39% were obtained. In simulated exudative microenvironment, water vapor transmission rate (WVTR) values around 700 g/m2/day were observed, while water vapor permeability rates (WVPR) reached about 300 g/m2/day. In simulated dehydrated microenvironment, values of WVTR around 200 g/m2/day and WVPR around 175 g/m2/day were attained.