Mucoadhesive capsules based on bacterial nanocellulose and chitosan as delivery system of turmeric extract.

Current efforts in stomach-related drug design focus on improving drug bioavailability within the gastric region. Bacterial nanocellulose (BNC) has been established as a suitable material for drug delivery systems; however, it lacks adhesion to the gastric environment. This limitation can be addressed by leveraging the mucoadhesive properties of low molecular weight chitosan (LMWC). Therefore, we aimed to develop mucoadhesive capsules constructed from BNC coated with crosslinked LMWC, intended for targeted drug delivery in the gastric region. The capsules were characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, and mucoadhesion assessments. Under acidic conditions, crosslinked chitosan exhibited enhanced swelling relative to neutral conditions. The coating of chitosan onto the BNC fibrillar network of the capsules resulted in the superimposition of vibration bands and enhanced thermal stability. Furthermore, the capsules exhibited significant mucoadhesive properties in the gastric environment, with an attachment force measuring 89.151 ± 6.226 mN. To validate the efficacy of the system, we utilized antioxidant turmeric extract (TE) as a bioactive compound with chemopreventive potential against stomach cancer. TE was adsorbed onto BNC in a reversible multilayer system, enabling controlled adsorption and desorption. These findings highlight the significance of developing mucoadhesive capsules as a tailored drug delivery system for gastric conditions, particularly in the context of treating stomach diseases as cancer.

Mechanisms of Action of Fruit and Vegetable Phytochemicals in Colorectal Cancer Prevention.

Colorectal cancer (CRC) is the third most common cancer worldwide and its incidence is expected to increase by almost 80% by 2030. CRC apparition is related to poor diet, mainly due to low consumption of phytochemicals present in fruits and vegetables. Hence, this paper reviews the most promising phytochemicals in the literature, presenting scientific evidence regarding potential CRC chemopreventive effects. Moreover, this paper reveals the structure and action of CRC mechanisms that these phytochemicals are involved in. The review reveals that vegetables rich in phytochemicals such as carrots and green leafy vegetables, as well as some fruits such as pineapple, citrus fruits, papaya, mango, and Cape gooseberry, that have antioxidant, anti-inflammatory, and chemopreventive properties can promote a healthy colonic environment. Fruits and vegetables in the daily diet promote antitumor mechanisms by regulating cell signaling and/or proliferation pathways. Hence, daily consumption of these plant products is recommended to reduce the risk of CRC.

Biomineralization in Three-Dimensional Scaffolds Based on Bacterial Nanocellulose for Bone Tissue Engineering: Feature Characterization and Stem Cell Differentiation.

Bacterial nanocellulose (BNC) has a negative surface charge in physiological environments, which allows the adsorption of calcium ions to initiate the nucleation of different calcium phosphate phases. The aim of this study was to investigate different methods of mineralization in three-dimensional microporous bacterial nanocellulose with the intention of mimicking the composition, structure, and biomechanical properties of natural bone. To generate the 3D microporous biomaterial, porogen particles were incorporated during BNC fermentation with the Komagataeibacter medellinensis strain. Calcium phosphates (CPs) were deposited onto the BNC scaffolds in five immersion cycles, alternating between calcium and phosphate salts in their insoluble forms. Scanning electron microscopy (SEM) showed that the scaffolds had different pore sizes (between 70 and 350 µm), and their porous interconnectivity was affected by the biomineralization method and time. The crystals on the BNC surface were shown to be rod-shaped, with a calcium phosphate ratio similar to that of immature bone, increasing from 1.13 to 1.6 with increasing cycle numbers. These crystals also increased in size with an increasing number of cycles, going from 25.12 to 35.9 nm. The main mineral phase observed with X-ray diffraction was octacalcium dihydrogen hexakis phosphate (V) pentahydrate (OCP). In vitro studies showed good cellular adhesion and high cell viability (up to 95%) with all the scaffolds. The osteogenic differentiation of human bone marrow mesenchymal stem cells on the scaffolds was evaluated using bone expression markers, including alkaline phosphatase, osteocalcin, and osteopontin. In conclusion, it is possible to prepare 3D BNC scaffolds with controlled microporosity that allow osteoblast adhesion, proliferation, and differentiation.

Advances in Tumor Organoids for the Evaluation of Drugs: A Bibliographic Review.

Tumor organoids are defined as self-organized three-dimensional assemblies of heterogeneous cell types derived from patient samples that mimic the key histopathological, genetic, and phenotypic characteristics of the original tumor. This technology is proposed as an ideal candidate for the evaluation of possible therapies against cancer, presenting advantages over other models which are currently used. However, there are no reports in the literature that relate the techniques and material development of tumor organoids or that emphasize in the physicochemical and biological properties of materials that intent to biomimicry the tumor extracellular matrix. There is also little information regarding the tools to identify the correspondence of native tumors and tumoral organoids (tumoroids). Moreover, this paper relates the advantages of organoids compared to other models for drug evaluation. A growing interest in tumoral organoids has arisen from 2009 to the present, aimed at standardizing the process of obtaining organoids, which more accurately resemble patient-derived tumor tissue. Likewise, it was found that the characteristics to consider for the development of organoids, and therapeutic responses of them, are cell morphology, physiology, the interaction between cells, the composition of the cellular matrix, and the genetic, phenotypic, and epigenetic characteristics. Currently, organoids have been used for the evaluation of drugs for brain, lung, and colon tumors, among others. In the future, tumor organoids will become closer to being considered a better model for studying cancer in clinical practice, as they can accurately mimic the characteristics of tumors, in turn ensuring that the therapeutic response aligns with the clinical response of patients.

Development of Genistein Drug Delivery Systems Based on Bacterial Nanocellulose for Potential Colorectal Cancer Chemoprevention: Effect of Nanocellulose Surface Modification on Genistein Adsorption.

Genistein is an isoflavone with antioxidant, anti-inflammatory, and anticancer properties. That said, its use in the industry is limited by its low solubility in aqueous systems. In this work, bacterial nanocellulose (BNC) and BNC modified with cetyltrimethylammonium (BNC-CTAB) were evaluated as genistein-encapsulating materials for their controlled release in cancer chemoprevention. Thin films were obtained and characterized by contact angle, AFM, TEM, UV-Vis spectroscopy FTIR, and TGA techniques to verify surface modification and genistein encapsulation. The results show a decrease in hydrophilization degree and an increase in diameter after BNC modification. Furthermore, the affinity of genistein with the encapsulating materials was determined in the context of monolayer and multilayer isotherms, thermodynamic parameters and adsorption kinetics. Spontaneous, endothermic and reversible adsorption processes were found for BNC-GEN and BNC-CTAB-GEN. After two hours, the maximum adsorption capacity corresponded to 4.59 mg GEN∙g-1 BNC and 6.10 mg GEN∙g-1 BNC-CTAB; the latter was a more stable system. Additionally, in vitro release assays performed with simulated gastrointestinal fluids indicated controlled and continuous desorption in gastric and colon fluids, with a release of around 5% and 85%, respectively, for either system. Finally, the IC50 tests made it possible to determine the amounts of films required to achieve therapeutic concentrations for SW480 and SW620 cell lines.

Evaluation of the Effects of Genistein In Vitro as a Chemopreventive Agent for Colorectal Cancer-Strategy to Improve Its Efficiency When Administered Orally.

Colorectal Cancer (CRC) ranks third in terms of incidence and second in terms of mortality and prevalence worldwide. In relation to chemotherapy treatment, the most used drug is 5-fluorouracil (5-FU); however, the use of this drug generates various toxic effects at the systemic level. For this reason, new therapeutic strategies are currently being sought that can be used as neoadjuvant or adjuvant treatments. Recent research has shown that natural compounds, such as genistein, have chemotherapeutic and anticancer effects, but the mechanisms of action of genistein and its molecular targets in human colon cells have not been fully elucidated. The results reported in relation to non-malignant cell lines are also unclear, which does not allow evidence of the selectivity that this compound may have. Therefore, in this work, genistein was evaluated in vitro in both cancer cell lines SW480 and SW620 and in the non-malignant cell line HaCaT. The results obtained show that genistein has selectivity for the SW480 and SW620 cell lines. In addition, it inhibits cell viability and has an antiproliferative effect in a dose-dependent manner. Increased production of reactive oxygen species (ROS) was also found, suggesting an association with the cell death process through various mechanisms. Finally, the encapsulation strategy that was proposed made it possible to demonstrate that bacterial nanocellulose (BNC) is capable of protecting genistein from the acidic conditions of gastric fluid and also allows the release of the compound in the colonic fluid. This would allow genistein to act locally in the mucosa of the colon where the first stages of CRC occur.

Assessment of Bacterial Nanocellulose Loaded with Acetylsalicylic Acid or Povidone-Iodine as Bioactive Dressings for Skin and Soft Tissue Infections.

Bacterial nanocellulose (BNC) is a novel nanomaterial known for its large surface area, biocompatibility, and non-toxicity. BNC contributes to regenerative processes in the skin but lacks antimicrobial and anti-inflammatory properties. Herein, the development of bioactive wound dressings by loading antibacterial povidone-iodine (PVI) or anti-inflammatory acetylsalicylic acid (ASA) into bacterial cellulose is presented. BNC is produced using Hestrin-Schramm culture media and loaded via immersion in PVI and ASA. Through scanning electron microscopy, BNC reveals open porosity where the bioactive compounds are loaded; the mechanical tests show that the dressing prevents mechanical wear. The loading kinetic and release assays (using the Franz cell method) under simulated fluids present a maximum loading of 589.36 mg PVI/g BNC and 38.61 mg ASA/g BNC, and both systems present a slow release profile at 24 h. Through histology, the complete diffusion of the bioactive compounds is observed across the layers of porcine skin. Finally, in the antimicrobial experiment, BNC/PVI produced an inhibition halo for Gram-positive and Gram-negative bacteria, confirming the antibacterial activity. Meanwhile, the protein denaturation test shows effective anti-inflammatory activity in BNC/ASA dressings. Accordingly, BNC is a suitable platform for the development of bioactive wound dressings, particularly those with antibacterial and anti-inflammatory properties.

Recent Advances in Polymer Nanomaterials for Drug Delivery of Adjuvants in Colorectal Cancer Treatment: A Scientific-Technological Analysis and Review.

Colorectal cancer (CRC) is the type with the second highest morbidity. Recently, a great number of bioactive compounds and encapsulation techniques have been developed. Thus, this paper aims to review the drug delivery strategies for chemotherapy adjuvant treatments for CRC, including an initial scientific-technological analysis of the papers and patents related to cancer, CRC, and adjuvant treatments. For 2018, a total of 167,366 cancer-related papers and 306,240 patents were found. Adjuvant treatments represented 39.3% of the total CRC patents, indicating the importance of adjuvants in the prognosis of patients. Chemotherapy adjuvants can be divided into two groups, natural and synthetic (5-fluorouracil and derivatives). Both groups can be encapsulated using polymers. Polymer-based drug delivery systems can be classified according to polymer nature. From those, anionic polymers have garnered the most attention, because they are pH responsive. The use of polymers tailors the desorption profile, improving drug bioavailability and enhancing the local treatment of CRC via oral administration. Finally, it can be concluded that antioxidants are emerging compounds that can complement today's chemotherapy treatments. In the long term, encapsulated antioxidants will replace synthetic drugs and will play an important role in curing CRC.

Development of novel three-dimensional scaffolds based on bacterial nanocellulose for tissue engineering and regenerative medicine: Effect of processing methods, pore size, and surface area.

Despite the efforts focused on manufacturing biological engineering scaffolds for tissue engineering and regenerative medicine, a biomaterial that meets the necessary characteristics for these applications has not been developed to date. Bacterial nanocellulose (BNC) is an outstanding biomaterial for tissue engineering and regenerative medicine; however, BNC's applications have been focused on two-dimensional (2D) medical devices, such as wound dressings. Given the need for three-dimensional (3D) porous biomaterials, this work evaluates two methods to generate (3D) BNC scaffolds. The structural characteristics and physicochemical, mechanical, and cell behaviour properties were evaluated. Likewise, the effects of the pore size and surface area in the mechanical performance of BNC biomaterials and their cell response in a fibroblast cell line are discussed for the first time. In this study, a new method is proposed for the development of 3D BNC scaffolds using paraffin wax. This new method is less time-consuming, more robust in removing the paraffin and less aggressive toward the BNC microstructure. Moreover, the biomaterial had regular porosity with good mechanical behaviour; the cells can adhere and increase in number without overcrowding. Regarding the pore size and surface area, highly interconnected porosities (measuring approximately 60 µm) and high surface area are advantageous for the biomaterial's mechanical properties and cell behaviour. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 348-359, 2019.

Effect of Different Carbon Sources on Bacterial Nanocellulose Production and Structure Using the Low pH Resistant Strain Komagataeibacter Medellinensis.

Bacterial cellulose (BC) is a polymer obtained by fermentation with microorganism of different genera. Recently, new producer species have been discovered, which require identification of the most important variables affecting cellulose production. In this work, the influence of different carbon sources in BC production by a novel low pH-resistant strain Komagataeibacter medellinensis was established. The Hestrin-Schramm culture medium was used as a reference and was compared to other media comprising glucose, fructose, and sucrose, used as carbon sources at three concentrations (1, 2, and 3% w/v). The BC yield and dynamics of carbon consumption were determined at given fermentation times during cellulose production. While the carbon source did not influence the BC structural characteristics, different production levels were determined: glucose > sucrose > fructose. These results highlight considerations to improve BC industrial production and to establish the BC property space for applications in different fields.