Nanocellulose/Nanoporous Silicon Composite Films as a Drug Delivery System.

Nanocellulose (NC) is a promising material for drug delivery due to its high surface area-to-volume ratio, biocompatibility, biodegradability, and versatility in various formats (nanoparticles, hydrogels, microspheres, membranes, and films). In this study, nanocellulose films were derived from "Bolaina blanca" (Guazuma crinita) and combined with nanoporous silicon microparticles (nPSi) in concentrations ranging from 0.1% to 1.0% (w/v), using polyvinyl alcohol (PVA) as a binding agent to create NC/nPSi composite films for drug delivery systems. The physicochemical properties of the samples were characterized using UV-Vis spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The mechanical properties and drug release capabilities were also evaluated using methylene blue (MB) as an antibacterial drug model. Antibacterial assays were conducted against S. aureus and E. coli bacteria. The results show that NC/nPSi composites with 1% nPSi increased the T50% by 10 °C and enhanced mechanical properties, such as a 70% increase in the elastic modulus and a 372% increase in elongation, compared to NC films. Additionally, MB released from NC/nPSi composites effectively inhibited the growth of both bacteria. It was also observed that the diffusion coefficients were inversely proportional to the % nPSi. These findings suggest that this novel NC/nPSi-based material can serve as an effective controlled drug release system.

Unraveling Drug Delivery from Cyclodextrin Polymer-Coated Breast Implants: Integrating a Unidirectional Diffusion Mathematical Model with COMSOL Simulations.

Breast cancer ranks among the most commonly diagnosed cancers worldwide and bears the highest mortality rate. As an integral component of cancer treatment, mastectomy entails the complete removal of the affected breast. Typically, breast reconstruction, involving the use of silicone implants (augmentation mammaplasty), is employed to address the aftermath of mastectomy. To mitigate postoperative risks associated with mammaplasty, such as capsular contracture or bacterial infections, the functionalization of breast implants with coatings of cyclodextrin polymers as drug delivery systems represents an excellent alternative. In this context, our work focuses on the application of a mathematical model for simulating drug release from breast implants coated with cyclodextrin polymers. The proposed model considers a unidirectional diffusion process following Fick's second law, which was solved using the orthogonal collocation method, a numerical technique employed to approximate solutions for ordinary and partial differential equations. We conducted simulations to obtain release profiles for three therapeutic molecules: pirfenidone, used for preventing capsular contracture; rose Bengal, an anticancer agent; and the antimicrobial peptide KR-12. Furthermore, we calculated the diffusion profiles of these drugs through the cyclodextrin polymers, determining parameters related to diffusivity, solute solid-liquid partition coefficients, and the Sherwood number. Finally, integrating these parameters in COMSOL multiphysics simulations, the unidirectional diffusion mathematical model was validated.

Plasmonic and Photothermal Effects of CuS Nanoparticles Biosynthesized from Acid Mine Drainage with Potential Drug Delivery Applications.

In this work, the plasmonic and photothermal effects of CuS nanoparticles biosynthesized from acid mine drainage (AMD) were studied. CuS were formed by delivering the H2S generated by a sulfidogenic bioreactor to an off-line system containing the AMD. The precipitates collected after contact for an hour were washed and physico-chemically characterized, showing a nanoparticle with a mean diameter of 33 nm, crystalline nature and semiconductor behavior with a direct band gap of 2.2 eV. Moreover, the CuS nanoparticles exhibited localized surface plasmonic resonance in the near infrared range, with a high absorption band centered at 973 nm of wavelength, which allowed an increase in the temperature of the surrounding media under irradiation. Finally, the cytotoxicity of the CuS nanoparticles as well as their potential use as part of drug delivery platforms were investigated.

Functionalization of breast implants by cyclodextrin in-situ polymerization: a local drug delivery system for augmentation mammaplasty.

Mammaplasty is a widely performed surgical procedure worldwide, utilized for breast reconstruction, in the context of breast cancer treatment, and aesthetic purposes. To enhance post-operative outcomes and reduce risks (hematoma with required evacuation, capsular contracture, implant-associated infection and others), the controlled release of medicaments can be achieved using drug delivery systems based on cyclodextrins (CDs). In this study, our objective was to functionalize commercially available silicone breast implants with smooth and textured surfaces through in-situ polymerization of two CDs: ß-CD/citric acid and 2-hydroxypropyl-ß-CD/citric acid. This functionalization serves as a local drug delivery system for the controlled release of therapeutic molecules that potentially can be a preventive treatment for post-operative complications in mammaplasty interventions. Initially, we evaluated the pre-treatment of sample surfaces with O2 plasma, followed by chitosan grafting. Subsequently, in-situ polymerization using both types of CDs was performed on implants. The results demonstrated that the proposed pre-treatment significantly increased the polymerization yield. The functionalized samples were characterized using microscopic and physicochemical techniques. To evaluate the efficacy of the proposed system for controlled drug delivery in augmentation mammaplasty, three different molecules were utilized: pirfenidone (PFD) for capsular contracture prevention, Rose Bengal (RB) as anticancer agent, and KR-12 peptide (KR-12) to prevent bacterial infection. The release kinetics of PFD, RB, and KR-12 were analyzed using the Korsmeyer-Peppas and monolithic solution mathematical models to identify the respective delivery mechanisms. The antibacterial effect of KR-12 was assessed against Staphylococcus epidermidis and Pseudomonas aeruginosa, revealing that the antibacterial rate of functionalized samples loaded with KR-12 was dependent on the diffusion coefficients. Finally, due to the immunomodulatory properties of KR-12 peptide on epithelial cells, this type of cells was employed to investigate the cytotoxicity of the functionalized samples. These assays confirmed the superior properties of functionalized samples compared to unprotected implants.

Effective Removal of Cu2+ Ions from Aqueous Media Using Poly(acrylamide-co-itaconic acid) Hydrogels in a Semi-Continuous Process.

Adsorption is one of the most crucial processes in water treatment today. It offers a low-cost solution that does not require specialized equipment or state-of-the-art technology while efficiently removing dissolved contaminants, including heavy metals. This process allows for the utilization of natural or artificial adsorbents or a combination of both. In this context, polymeric materials play a fundamental role, as they enable the development of adsorbent materials using biopolymers and synthetic polymers. The latter can be used multiple times and can absorb large amounts of water per gram of polymer. This paper focuses on utilizing adsorption through hydrogels composed of poly(acrylamide-co-itaconic acid) for removing Cu2+ ions dissolved in aqueous media in a semi-continuous process. The synthesized hydrogels were first immersed in 0.1 M NaOH aqueous solutions, enabling OH- ions to enter the gel matrix and incorporate into the polymer surface. Consequently, the copper ions were recovered as Cu(OH)2 on the surface of the hydrogel rather than within it, allowing the solid precipitates to be easily separated by decantation. Remarkably, the hydrogels demonstrated an impressive 98% removal efficiency of the ions from the solution in unstirred conditions at 30 °C within 48 h. A subsequent study involved a serial process, demonstrating the hydrogels' reusability for up to eight cycles while maintaining their Cu2+ ion recovery capacity above 80%. Additionally, these hydrogels showcased their capability to remove Cu2+ ions even from media with ion concentrations below 100 ppm.

Sulfidogenic Bioreactor-Mediated Formation of ZnS Nanoparticles with Antimicrobial and Photocatalytic Activity.

The use of sulfidogenic bioreactors is a biotechnology trend to recover valuable metals such as copper and zinc as sulfide biominerals from mine-impacted waters. In the present work, ZnS nanoparticles were produced using "green" H2S gas generated by a sulfidogenic bioreactor. ZnS nanoparticles were physico-chemically characterized by UV-vis and fluorescence spectroscopy, TEM, XRD and XPS. The experimental results showed spherical-like shape nanoparticles with principal zinc-blende crystalline structure, a semiconductor character with an optical band gap around 3.73 eV, and fluorescence emission in the UV-visible range. In addition, the photocatalytic activity on the degradation of organic dyes in water, as well as bactericidal properties against several bacterial strains, were studied. ZnS nanoparticles were able to degrade methylene blue and rhodamine in water under UV radiation, and also showed high antibacterial activity against different bacterial strains including Escherichia coli and Staphylococcus aureus. The results open the way to obtain valorous ZnS nanoparticles from the use of dissimilatory reduction of sulfate using a sulfidogenic bioreactor.

Coatings of Cyclodextrin/Citric-Acid Biopolymer as Drug Delivery Systems: A Review.

In the early 2000s, a method for cross-linking cyclodextrins (CDs) with citric acid (CTR) was developed. This method was nontoxic, environmentally friendly, and inexpensive compared to the others previously proposed in the literature. Since then, the CD/CTR biopolymers have been widely used as a coating on implants and other materials for biomedical applications. The present review aims to cover the chemical properties of CDs, the synthesis routes of CD/CTR, and their applications as drug-delivery systems when coated on different substrates. Likewise, the molecules released and other pharmaceutical aspects involved are addressed. Moreover, the different methods of pretreatment applied on the substrates before the in situ polymerization of CD/CTR are also reviewed as a key element in the final functionality. This process is not trivial because it depends on the surface chemistry, geometry, and physical properties of the material to be coated. The biocompatibility of the polymer was also highlighted. Finally, the mechanisms of release generated in the CD/CTR coatings were analyzed, including the mathematical model of Korsmeyer-Peppas, which has been dominantly used to explain the release kinetics of drug-delivery systems based on these biopolymers. The flexibility of CD/CTR to host a wide variety of drugs, of the in situ polymerization to integrate with diverse implantable materials, and the controllable release kinetics provide a set of advantages, thereby ensuring a wide range of future uses.

Cost Function Analysis Applied to Different Kinetic Release Models of Arrabidaea chica Verlot Extract from Chitosan/Alginate Membranes.

This work focuses on the mathematical analysis of the controlled release of a standardized extract of A. chica from chitosan/alginate (C/A) membranes, which can be used for the treatment of skin lesions. Four different types of C/A membranes were tested: a dense membrane (CA), a dense and flexible membrane (CAS), a porous membrane (CAP) and a porous and flexible membrane (CAPS). The Arrabidae chica extract release profiles were obtained experimentally in vitro using PBS at 37 °C and pH 7. Experimental data of release kinetics were analyzed using five classical models from the literature: Zero Order, First Order, Higuchi, Korsmeyer-Peppas and Weibull functions. Results for the Korsmeyer-Peppas model showed that the release of A. chica extract from four membrane formulations was by a diffusion through a partially swollen matrix and through a water filled network mesh; however, the Weibull model suggested that non-porous membranes (CA and CAS) had fractal geometry and that porous membranes (CAP and CAPS) have highly disorganized structures. Nevertheless, by applying an explicit optimization method that employs a cost function to determine the model parameters that best fit to experimental data, the results indicated that the Weibull model showed the best simulation for the release profiles from the four membranes: CA, CAS and CAP presented Fickian diffusion through a polymeric matrix of fractal geometry, and only the CAPS membrane showed a highly disordered matrix. The use of this cost function optimization had the significant advantage of higher fitting sensitivity.

Controlled Release of Caffeic Acid and Pinocembrin by Use of nPSi-ßCD Composites Improves Their Antiangiogenic Activity.

Although polyphenols have great pharmacological potential, the main disadvantage is that they have low bioavailability at the desired site. Thus, the use of biocompatible systems for drug delivery is a strategy that is currently gaining great interest. The objective of this study is to evaluate the effect of microencapsulation of caffeic acid and pinocembrin on the antioxidant and antiangiogenic activity of both polyphenols, by the use of nPSi-ßCD composite microparticles. For this HUVEC, cells were exposed to H2O2 and to treatments with polyphenols in solution and loaded in the composite microparticle. The polyphenols were incorporated into a microparticle using nanoporous silicon, chitosan and a ß-cyclodextrin polymer as the biomaterial. The evaluation of the antiangiogenic effect of the treatments with polyphenols in solution and microencapsulated was carried out through functional tests, and the changes in the expression of target genes associated with the antioxidant pathway and angiogenesis was performed through qPCR. The results obtained show that the caffeic acid and pinocembrin have an antioxidant and antiangiogenic activity, both in solution as microencapsulated. In the caffeic acid, a greater biological effect was observed when it was incorporated into the nPSi-ßCD composite microparticle. Our results suggest that the nPSi-ßCD composite microparticle could be used as an alternative oral drug administration system.

Hybrid porous silicon/green synthetized Ag microparticles as potential carries for Ag nanoparticles and drug delivery.

In the present work, the fabrication of hybrid porous silicon/green synthetized Ag microparticles was shown and the potential use as carriers for Ag nanoparticles and drug delivery was explored. Hybrid microparticles were fabricated by incorporating green synthetized Ag nanoparticles into porous silicon matrix. The main physicochemical characteristics of the hybrid systems were studied by several techniques including UV-vis spectroscopy, TEM, SEM, XRD and XPS. The toxicology of these hybrid systems was investigated by cell viability, MTT, and comet assays. In addition, the possibility to aggregate different drug to use as drug delivery system was demonstrated by using florfenicol as drug model, due to its importance in salmon industry. The experimental results showed the potential to use these hybrid systems as carries for drug delivery in salmon industry.

Fabrication and characterization of nanostructured porous silicon-silver composite layers by cyclic deposition: dip-coating vs spin-coating.

Composites of nanostructured porous silicon and silver (nPSi-Ag) have attracted great attention due to the wide spectrum of applications in fields such as microelectronics, photonics, photocatalysis and bioengineering, Among the different methods for the fabrication of nanostructured composite materials, dip and spin-coating are simple, versatile, and cost-effective bottom-up technologies to provide functional coatings. In that sense, we aimed at fabricating nPSi-Ag composite layers. Using nPSi layers with pore diameter of 30 nm, two types of thin-film techniques were systematically compared: cyclic dip-coating (CDC) and cyclic spin-coating (CSC). CDC technique formed a mix of granular and flake-like structures of metallic Ag, and CSC method favored the synthesis of flake-like structures with Ag and Ag2O phases. Flakes obtained by CDC and CSC presented a width of 110 nm and 70 nm, respectively. Particles also showed a nanostructure surface with features around 25 nm. According to the results of EDX and RBS, integration of Ag into nPSi was better achieved using the CDC technique. SERS peaks related to chitosan adsorbed on Ag nanostructures were enhanced, especially in the nPSi-Ag composite layers fabricated by CSC compared to CDC, which was confirmed by FTDT simulations. These results show that CDC and CSC produce different nPSi-Ag composite layers for potential applications in bioengineering and photonics.

c-di-GMP-related phenotypes are modulated by the interaction between a diguanylate cyclase and a polar hub protein.

c-di-GMP is a major player in the switch between biofilm and motile lifestyles. Several bacteria exhibit a large number of c-di-GMP metabolizing proteins, thus a fine-tuning of this nucleotide levels may occur. It is hypothesized that some c-di-GMP metabolizing proteins would provide the global c-di-GMP levels inside the cell whereas others would maintain a localized pool, with the resulting c-di-GMP acting at the vicinity of its production. Although attractive, this hypothesis has yet to be demonstrated in Pseudomonas aeruginosa. We found that the diguanylate cyclase DgcP interacts with the cytosolic region of FimV, a polar peptidoglycan-binding protein involved in type IV pilus assembly. Moreover, DgcP is located at the cell poles in wild type cells but scattered in the cytoplasm of cells lacking FimV. Overexpression of dgcP leads to the classical phenotypes of high c-di-GMP levels (increased biofilm and impaired motilities) in the wild-type strain, but not in a ΔfimV background. Therefore, our findings suggest that DgcP activity is regulated by FimV. The polar localization of DgcP might contribute to a local c-di-GMP pool that can be sensed by other proteins at the cell pole, bringing to light a specialized function for a specific diguanylate cyclase.

Use of nPSi-ßCD Composite Microparticles for the Controlled Release of Caffeic Acid and Pinocembrin, Two Main Polyphenolic Compounds Found in a Chilean Propolis.

Propolis is widely recognized for its various therapeutic properties. These are attributed to its rich composition in polyphenols, which exhibit multiple biological properties (e.g., antioxidant, anti-inflammatory, anti-angiogenic). Despite its multiple benefits, oral administration of polyphenols results in low bioavailability at the action site. An alternative to face this problem is the use of biomaterials at nano-micro scale due to its high versatility as carriers and delivery systems of various drugs and biomolecules. The aim of this work is to determine if nPSi-ßCD microparticles are a suitable material for the load and controlled release of caffeic acid (CA) and pinocembrin (Pin), two of the main components of a Chilean propolis with anti-atherogenic and anti-angiogenic activity. Polyphenols and nPSi-ßCD microparticles cytocompatibility studies were carried out with human umbilical vein endothelial cells (HUVECs). Results from physicochemical characterization demonstrated nPSi-ßCD microparticles successfully retained and controlled release CA and Pin. Furthermore, nPSi-ßCD microparticles presented cytocompatibility with HUVECs culture at concentrations of 0.25 mg/mL. These results suggest that nPSi-ßCD microparticles could safely be used as an alternate oral delivery system to improve controlled release and bioavailability of CA or Pin-and eventually other polyphenols-thus enhancing its therapeutic effect for the treatment of different diseases.

Synthesis and Properties of Silk Fibroin/Konjac Glucomannan Blend Beads.

Silk fibroin (SF) and konjac glucomannan (KGM) are promising materials in the biomedical field due to their low toxicity, biocompatibility, biodegradability and low immune response. Beads of these natural polymers are interesting scaffolds for biomedical applications, but their fabrication is a challenge due to their low stability and the necessary adaptation of their chemical and mechanical properties to be successfully applied. In that sense, this study aimed to synthesize a blend of silk fibroin and konjac glucomannan (SF/KGM) in the form of porous beads obtained through dripping into liquid nitrogen, with a post-treatment using ethanol. Intermolecular hydrogen bonds promoted the integration of SF and KGM. Treated beads showed higher porous size, crystallinity, and stability than untreated beads. Characterization analyses by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric (TGA), and X-ray diffraction (XDR) evidenced that ethanol treatment allows a conformational transition from silk I to silk II in SF and an increase in the KGM deacetylation. Those chemical changes significantly enhanced the mechanical resistance of SF/KGM beads in comparison to pure SF and KGM beads. Moreover, samples showed cytocompatibility with HaCaT and BALB/c 3T3 cells.