Development of a cationic bacterial cellulose film loaded with anionic liposomes for prolonged release of oxacillin in wound dressing applications.

Dressings should protect wounds, promote healing, absorb fluids, and maintain moisture. Bacterial cellulose is a biopolymer that stands out in biomaterials due to its high biocompatibility in several applications. In the area of dressings, it is already marketed as an alternative to traditional dressings. However, it lacks any intrinsic activity; among these, the need for antimicrobial activity in infected wounds stands out. We developed a cationic cellulose film by modifying cellulose with 1-(5-carboxypentyl)pyridin-1-ium bromide, enhancing its wettability (contact angle: 26.6°) and water retention capacity (2714.37 %). This modified film effectively retained oxacillin compared to the unmodified control. Liposomal encapsulation further prolonged oxacillin release up to 11 days. Both oxacillin-loaded films and liposomal formulations demonstrated antimicrobial activity against Staphylococcus aureus. Our findings demonstrate the potential of chemically modified cellulose as a platform for controlled anionic antibiotics and/or their formulations delivery in wound care.

Lignocellulosic-biomolecules conjugated systems: green-engineered complexes modified by covalent linkers.

Lignocellulosic biomass represents an abundant and eco-friendly material widely explored in recent years. The main lignocellulosic fractions include cellulose, hemicellulose, and lignin. Nonetheless, the heterogeneity and complexity of these components pose challenges in achieving the desired properties. Conversely, their attractive functional groups can covalently link with other biomolecules, facilitating the creation and enhancement of material properties. Lignocellulosic molecules can form different linkages with other biomolecules through classic and modern methods. Bioconjugation has emerged as a suitable alternative to create new nuances, empowering the linkage between lignocellulosic materials and biomolecules through linkers. These conjugates (lignocellulosic-linkers-biomolecules) attract attention from stakeholders in medicine, chemistry, biology, and agriculture. The plural formations of these biocomplexes highlight the significance of these arrangements. Therefore, this review provides an overview of the progress of lignocellulosic-biomolecule complexes and discusses different types of covalent bioconjugated systems, considering the formation of linkers, applicability, toxicity, and future challenges.

Papain Covalent Immobilization in Bacterial Cellulose Films as a Wound Dressing.

Ideally, the dressings used in the clinic have characteristics that help the wound closure process. Among several factors that affect the success of this healing process, there is debridement. It manages the wound bed components and the re-epithelialization process. Still, the property of debridement is not generally associated with dressings. Here, we show a chemically modified bacterial cellulose film conjugated to a proteolytic enzyme, papain, as a dressing with debridement properties. Bacterial cellulose films were reacted with a spacer derived from succinic acid and finally had this enzyme covalently immobilized in its structure by an amide bond. FT-IR and UV-vis showed bands typically of bioconjugated polymer. Enzymatic immobilization was very effective under the conditions applied with high yield (33% w/w), and these remained activated after the coupling reaction. The bacterial cellulose film with the enzyme papain attached to it was also very compatible with fibroblast cells, suggesting that it could be a promising wound dressing material for future research.

Liposome surface modification by phospholipid chemical reactions.

Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug delivery, diagnosis, and in many other academic areas. A novel class of this nanoparticle is the actively target liposome, which is constructed with the surface modified with appropriated molecules (or ligands) to actively bind a target molecule of certain cells, system, or tissue. There are many ways to functionalize these nanostructures, from non-covalent adsorption to covalent bond formation. In this review, we focus on the strategies of modifying liposomes by glycerophospholipid covalent chemical reaction. The approach used in this text summarizes the main reactions and strategies used in phospholipid modification that can be carried out by chemists and researchers from other areas. The knowledge of these methodologies is of great importance for planning new studies using this material and also for manipulating its properties.

Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability.

The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to­lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 µM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV-vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.

Enhancement of fibroblast growing on the mannosylated surface of cellulose membranes.

Bacterial cellulose membrane is a biomaterial with high value in the biomedical field. Many groups have been making efforts to promote chemical modifications of its structure and, consequently, add new characteristics. Recently, our group has developed a methodology to insert monoester succinic acid in bacterial cellulose membrane without disrupting the microfibril network and bind a protein on it. Considering the role of carbohydrates in the molecular recognition process in biological events, we continued these studies by inserting covalently multiples copies of aryl monosaccharide to bacterial cellulose succinylated and to study the in vitro tissue compatibility using fibroblasts. The mix of synthetical chemistry and material modification was performed to prepare aminoaryl mannoside and conjugate it, via amide bond using ultrasonic irradiation, to succinic group of bacterial cellulose. This material was characterized chemically (IR, UV-vis, 13C NMR CP-MAS) and physically (TGA and AFM). Mannosylated cellulose showed good in vitro compatibility with fibroblasts demonstrating its potential in the tissue engineering field which could provide a tissue compatible scaffold.

Target-Guided Synthesis and Antiplasmodial Evaluation of a New Fluorinated 3-Alkylpyridine Marine Alkaloid Analog.

The need to develop new alternatives for antimalarial treatment is urgent. Herein, we report the synthesis and antimalarial evaluation of a small library of synthetic 3-alkylpyridine marine alkaloid (3-APA) analogs. First, the compounds were evaluated in vitro against Plasmodium falciparum. The most active compound 5c was selected for optimization of its antimalarial properties. An in silico approach was used based on pure ab initio electronic structure prediction, and the results indicated that a substitution of the hydroxyl group by a fluorine atom could favor a more stable complex with heme at a molecular ratio of 2:1 (heme/3-APA halogenated). A new fluorinated 3-APA analog was synthesized (compound 7), and its antimalarial activity was re-evaluated. Compound 7 exhibited optimized antimalarial properties (P. falciparum IC50 = 2.5 µM), low genotoxicity, capacity to form a more stable heme/3-APA complex at a molecular ratio of 2:1, and conformity to RO5. The new compound, therefore, has great potential as a new lead antimalarial agent.

Revealing the Binding Process of New 3-Alkylpyridine Marine Alkaloid Analogue Antimalarials and the Heme Group: An Experimental and Theoretical Investigation.

Synthetic 3-alkylpyridine marine alkaloid (3-APA) analogues have shown good antimalarial activity against Plasmodium falciparum. However, despite their structural originality, their molecular target was unknown. Herein, we report a proposal for the antimalarial mechanism of action of 3-APA analogues through interference with the process of hemozoin (Hz) formation. The interaction between 3-APA analogues and heme groups was investigated employing an in silico approach and biophysical techniques such as ultraviolet-visible light (UV-vis) titration and electrospray ionization-mass spectrometry (ESI-MS). The in silico approach was performed based on pure ab initio electronic structure methods in order to obtain insights at the molecular level concerning the binding process of antimalarial drugs at their target site, the heme group. In silico results showed that the formation of heme:3-APA complexes at a molecular ratio of 2:1 are more stable than 1:1 complexes. These results were further confirmed by experimental techniques, such as UV-vis and high-resolution mass spectrometry (ESI-TOF), for two of the most active 3-APA analogues.