Histidine-Rich Protein Accelerates the Biomineralization of Zeolitic Imidazolate Frameworks for In Vivo Protein Delivery.

Biomineralization of metal-organic frameworks (MOFs) provides a powerful approach for intracellular protein delivery, enabling the study of biological function and therapeutic potential of proteins. However, the potency of this approach is largely challenged by the low efficiency of current strategies for interfacing proteins with MOFs for biomineralization and intracellular delivery. Here, we report a versatile and convenient biomineralization strategy for the rapid encapsulation and enhanced delivery of proteins using MOFs, accelerated by histidine-rich proteins. We demonstrate that the histidine-rich green fluorescent protein (H39GFP) can accelerate the biomineralization of MOFs by promoting the coordination between proteins and metal ions, leading to enhanced protein delivery efficiency up to 15-fold. Moreover, we show that the delivery of H39GFP-fused cytotoxic ribonuclease and bacterial-derived RAS protease can effectively inhibit tumor cell growth. The strategy of promoting the biomineralization of MOFs via histidine-rich proteins for enhanced intracellular delivery could be expanded to other biomacromolecules, advancing their therapeutic potential and the biomedical scope of MOFs.

Fabrication of baicalein-encapsulated zeolitic imidazole framework as a novel nanocomposited wound closure material to persuade pH-responsive healing efficacy in post-caesarean section wound care.

Baicalein is a plant-derived compound, it has widespread attention among biomedical researchers due to its biocompatibility and efficient biological activities. But it has non-solubility in physiological conditions and short bioavailability in the clinical process. The Discovery of a stimuli-based drug delivery system (DDS) is a perfect strategy to improve the bioactivity of baicalin in post-caesarean section wound care. We prepared a baicalein-encapsulated pH-responsive DDS with a zeolite imidazole framework-8 (ZIF-8) as a carrier. We investigated the material characteristics of DDS in terms of crystal structure, surface area morphology, particle size, FTIR, UV-vis, Powder XRD, and BET analysis techniques. The in vitro cytotoxicity, biocompatibility, and cell proliferation properties of BA@ZIF-8 were assessed against human fibroblast L929 cells. In vitro studies showed that BA@ZIF-8 nanocomposite significantly enhanced the biocompatibility against L929 cells after 72 h post-exposure. The pH-responsive drug release kinetics shows excellent baicalein release under acidic conditions and without unwanted drug release in physiological conditions. Wound scratch assay results revealed, that BA@ZIF-8 nanocomposite-treated cells exhibit the fastest cell proliferation and migration process in a very short period. In the antibacterial activity study, nanocomposite exposed dose depended on inhibition against wound infectious pathogens. The overall study signifies that BA@ZIF-8 nano-DDSs are effective and suitable DDS for stimuli-based post-caesarean section wound care.

ZIF-based carbon dots with lysosome-Golgi transport property as visualization platform for deep tumour therapy via hierarchical size/charge dual-transform and transcytosis.

The poor penetration of nanomaterials in solid tumours and difficulty in monitoring their penetration depth are major obstacles in their application for the treatment of solid tumours. Herein, pH-responsive carbon dots (ZCD) based on a zeolitic imidazolate framework (ZIF-8) were fabricated to achieve the deep delivery of the chemotherapeutic doxorubicin (DOX) via a hierarchical size/charge dual-transformation and transcytosis. The as-prepared ZCD accumulated in the solid tumour and the acidic tumour microenvironment further triggered its decomposition. Firstly, ZCD was decomposed by the weakly acidic extracellular microenvironment of the solid tumour, enabling it to transform into small and neutrally charged particles. Subsequently, these particles were endocytosed by lysosomes, and further disintegrated into smaller and positively charged particles, which could target the Golgi apparatus. Consequently, ZCD delivered DOX deep into the solid tumour via a size-shrinking strategy and Golgi-mediated transcytosis, thus significantly improving its antitumour efficacy. In addition, carbonization endowed ZCD with superior fluorescence property, which was enhanced in the acidic microenvironment, thus improving the sensitivity and accuracy of ex vivo monitoring of the penetration depth of the nanomedicine in real time. Collectively, our results confirmed that the carbon dots obtained via the direct carbonization of ZIF-8 simultaneously exhibited enhanced deep penetration into solid tumours and fluorescence, which could be monitored, and that the carbonization of functional materials is effective to enhance their fluorescence, and further broaden their applications.

A biomimetic zeolite-based nanoenzyme contributes to neuroprotection in the neurovascular unit after ischaemic stroke via efficient removal of zinc and ROS.

Zeolite-based nanomaterials have a large number of applications in the field of medicine due to their high porosity, biocompatibility and biological stability. In this study, we designed cerium (Ce)-doped Linde Type A (LTA) zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme to reduce dysfunction of the neurovascular unit (NVU) and attenuate cerebral ischaemia-reperfusion (I/R) injury. Owing to its unique adsorption capacity and mimetic catalytic activities, Ce@Zeo-NMs adsorbed excess zinc ions and exhibited scavenging activity against reactive oxygen species (ROS) induced by acute I/R, thus reshaping the oxidative and zinc microenvironment in the ischaemic brain. In vivo results demonstrated that Ce@Zeo-NMs significantly reduced ischaemic damage to the NVU by decreasing the infarct area, protecting against breakdown of the blood-brain barrier (BBB) via inhibiting the degradation of tight junction proteins (TJPs) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Taken together, these findings indicated that Ce@Zeo-NMs may serve as a promising dual-targeting therapeutic agent for alleviating cerebral I/R injury. STATEMENT OF SIGNIFICANCE: Cerium (Ce)-doped Linde Type A zeolite-based nanomaterials (Ce/Zeo-NMs) as a multifunctional mesoporous nanoenzyme were designed for inducing neuroprotection after ischaemic stroke by reducing dysfunction of the neurovascular unit (NVU). Ce@Zeo-NMs had the ability to adsorb excessive Zn2+ and showed mimetic enzymatic activities. As a result, Ce@Zeo-NMs protected against cerebral ischaemia and reduced the damage of NVU by improving the integrity of blood brain barrier (BBB) and inhibiting activation of microglia and astrocytes in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). These findings indicated that Ce@Zeo-NMs may serve as a therapeutic strategy for neuroprotection and functional recovery upon ischaemic stroke onset.

Synthetic Zeolite Supplementation as a Potential Candidate for the Therapy of Diabetic Syndrome.

<b>Background and Objective:</b> Natural and Synthetic Zeolite (SZ) is potentially useful for biopharmaceuticals and bio tools due to its unique and outstanding physical and chemical properties. Thus, the present study aimed to evaluate the possible effect of synthetic zeolite in (STZ)-induced diabetic rats. <b>Materials and Methods:</b> About 4 groups of rats were used, (I) normal control, (II) SZ group, (300 mg/kg/day), (III) STZ group, diabetic rats acted as positive control and (IV) STZ+SZ group, included diabetic rats treated with synthetic zeolite (300 mg/kg/day), statistical analysis comparisons between means were carried out using one-way analysis of variance (ANOVA) followed by a post hock (Tukey) multiple comparisons test at p<u>></u>0.05. <b>Results:</b> After six weeks, treatment of diabetic animals with synthetic zeolite markedly exhibited a significant reduction in glucose, lipids, DNA fragmentation, Alanine Aminotransferase (ALAT), Aspartate Aminotransferase (ASAT), urea, creatinine, Malondialdehyde (MDA) and Nitric Oxide (NO) levels concomitant with a significant rise in insulin, Glutathione (GSH), Superoxide Dismutase (SOD) and Catalase (CAT) values close to the corresponding values of healthy ones. <b>Conclusion:</b> In conclusion, synthetic zeolite exhibits multi-health benefits with promising potentials against STZ-induced diabetes, this behaviour may be attributed to its antioxidant and free radical scavenging mechanisms.

Near-Infrared Radiation-Assisted Drug Delivery Nanoplatform to Realize Blood-Brain Barrier Crossing and Protection for Parkinsonian Therapy.

Mitochondrial dysfunction, which is directly involved in Parkinson's disease (PD), is characterized by the production of reactive oxygen species (ROS) and aberrant energy metabolism. Thus, regulating mitochondrial function might be an effective strategy to treat PD. However, the blood-brain barrier (BBB) presents a significant challenge for the intracerebral delivery of drugs. Here, we synthesized a zeolitic imidazolate framework 8-coated Prussian blue nanocomposite (ZIF-8@PB), which was encapsulated with quercetin (QCT), a natural antioxidant, to treat PD. ZIF-8@PB-QCT exhibited superior near-infrared radiation (NIR) response and penetrated through the BBB to the site of mitochondrial damage guided by the photothermal effect. In the mice model of PD, the QCT released from ZIF-8@PB-QCT significantly increased the adenosine triphosphate levels, reduced the oxidative stress levels, and reversed dopaminergic neuronal damage as well as PD-related behavioral deficits without any damage to the normal tissues. Furthermore, we explored the underlying neuroprotective mechanism of ZIF-8@PB-QCT that was mediated by activating the PI3K/Akt signaling pathway. Thus, combined with noninvasive NIR radiation, the biocompatible ZIF-8@PB-QCT nanocomposite could be used to treat neurodegenerative diseases.

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial.

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

Role of Compositum Zeolite® in management of inflammatory bowel disease: a pilot study.

BACKGROUND: Zeolites are crystalline mineral aluminosilicate compounds with microporous structures of tetrahedrons and huge porosity. In the gut, these silicates act as adsorbents, ion-exchangers, catalysts, detergents or antidiarrheic agents. In addition to its well-known antioxidant effect, a new potential advantage of Zeolite could be the microbiome modulation. In this scenery, we aimed to investigate the effect of this compound on inflammation among inflammatory bowel disease patients, assessing both clinical activity and inflammatory markers. METHODS: This was an open one branch pilot study involving 20 IBD patients, both affected with Crohn's disease and ulcerative colitis affering to San Giovanni Antica Sede Hospital, Città della Salute e della Scienza in Turin. Each patient was given Compositum Zeolite® 6 g/die for 56 days; follow-up time was 60 days from the end of Zeolite therapy. Primary outcomes of the study were to evaluate the improvement of the quality of life (Partial Mayo score or Harvey Bradshaw Index) and the compliance to therapy, while secondary outcome was the reduction of calprotectin value. RESULTS: Of the twenty patients enrolled, 4 did not attend the scheduled check-up visit and 2 reported non-adherence to the therapy with Compositum Zeolite® so these 6 patients were considered as drop out and their data were not included in statistical analysis. So, compliance rate was 70%, that is similar to general adherence to therapy in our setting. Regarding Ulcerative Colitis patients, at the moment of enrolment mean Mayo Partial Score (MPS) was 3.09 (CI: 1.76-4.41) while after 8 weeks of Compositum Zeolite® supplementation the mean MPS was 2.72 (CI: 1.45-4.00) (P=0.57) and after 60 days of follow-up mean MPS was 1.9 (CI: 0.85-2.97) (P=0.24). As Crohn's disease patients are concerned, HBI Score at enrolment was 5.3 (CI: 3.38-7.29) while mean score after 8 week of therapy was 4 (CI: 2.85-5.15) (P=0.042) and after 60 days of follow-up mean score was 3.1 (CI: 1.48-4.87) (P=0.18). Mean calprotectin value at enrolment was 925.64 (CI: 451.83-1399.45). while after 2 months of Compositum Zeolite® addon therapy was 952.72 (CI: 492.73-1412.73); P value 0.93. After 2 months of follow-up mean value was 724.45 (CI: 240.15-1208.73) P value 0.3. CONCLUSIONS: Compositum Zeolite® has a compliance rate similar to the other prescribed therapies and is a good addon therapy to improve activity indexes, mainly in Crohn's disease. It also seems to improve inflammatory indexes, even if maybe dose or time of therapy were insufficient to reach a full negativization of these parameters.

Recent advancement of imidazolate framework (ZIF-8) based nanoformulations for synergistic tumor therapy.

As a new kind of porous material, zeolitic imidazolate frameworks (ZIF-8) are built from zinc ions and 2-methylimidazolate and possess unique merits including high porosity, good structural regularity and tunability, adjustable surface functionality and intrinsic pH induced biodegradability. These advantages endow ZIF-8 with multiple functionalities and stimuli-responsive controlled release of loaded payloads by endogenous or exogenous means. In this review, we will summarize the recent advancement of ZIF-8 as nanocarriers for the loading of various molecules including chemotherapeutic drugs, photosensitizers, photothermal agents, and proteins to fabricate multifunctional nanocomposites for synergistic cancer therapy. In addition, the challenges and future developments in this area will be highlighted.

Efficacy of Detoxsan® powder on diarrhea caused by gastrointestinal neuroendocrine tumors.

BACKGROUND: Patients with neuroendocrine tumors (NETs) of the gastrointestinal tract suffer frequently from chronic diarrhea. A well characterized medical advice containing zeolite (Detoxsan® powder) was applied to patients suffered from therapy-refractory diarrhea either by its frequency or by watery stool, despite receiving standard pharmacotherapy according to the guidelines for carcinoid syndrome and comorbidities. Detoxsan® powder acts as an adsorbent and might reduce significantly symptoms of diarrhea in patients suffering from NETs. AIM: To overcome the therapy-refractory diarrhea of patients with NETs by the zeolite containing medical advice Detoxsan® powder. METHODS: A total of 20 patients (12 female and 8 male) suffering from diarrhea either by its frequency or from watery stool caused by NETs were included. In each patient, the diagnosis had been confirmed by histology and somatostatin receptors expression proven by positron emission tomography/computed tomography using Ga-68-labeled somatostatin analogs. All patients received standard-of-care pharmacotherapy and were additionally given Detoxsan® powder as an extemporaneous drug containing 90% natural Cuban zeolite and 10% magnesium aspartate. Recommended daily dosage ranges between 3 g once to three times per day. Each day dose and bowel movements were documented by the patients themselves in a pre-defined table. Additionally to the bowel movements quantitative determinations of serotonin, urea, creatinine and single ions were performed within the serum of the patients by commercially available equipment used as a matter of routine in the clinic. RESULTS: All patients enrolled in this pilot study did not only suffer from NETs, but also from comorbidities and treatment-resistant diarrhea. There was insufficient control of diarrhea, most probably due to the secretion of hormones like serotonin produced by the slowly growing and highly differentiated NETs. All patients only took Detoxsan® powder as an antidiarrheal drug. In general, response effects need several days to become perceptible and require an intake of Detoxsan® powder for an extended time period or intermittently, if persisting stabilization of bowel movements could not be achieved. A correlation between NET grade, part and size of bowel resection and functionality of the tumor could not be demonstrated. Therefore, diarrhea seemed to be based on the metabolic activity of the well-differentiated NETs, which eventually led to treatment resistance. In summary, 14 out of the 20 patients (70%) declared to be very content with using Detoxsan® powder and observed a significant reduction of diarrhea, while the effective dose and intake period that resulted in a symptom relief varied individually. CONCLUSION: Detoxsan® powder is able to reduce significantly symptoms of NET-related diarrhea in the majority of patients. The duration of taking Detoxsan® powder and its dosage vary individually.

Zeolite Clinoptilolite: Therapeutic Virtues of an Ancient Mineral.

Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO4 and SiO4 that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.

Zeolite-fibrin clot composite as a haemostatic agent for haemophilia A.

Zeolite is a multifunctional material, which recently exhibited promising prospects in emerging biological and medical applications. This study reported a new bio-inorganic hybrid of zeolite-fibrin clot composite serving as haemostatic agent in haemophilia A. The zeolite-fibrin clot composite promoted haemocompatibility and helped to achieve short clotting time both in vitro (22 ± 3 s vs. >600 s) and in vivo (4.5 min vs. >60 min) compared to control in coagulation factor VIII deficiency bleeding model. Therefore, in situations of surgical operation or accidental injury, this effective and ready-to-use haemostatic agent may provide rapid haemostasis for haemophilia A patients.

Applications of zeolites in biotechnology and medicine - a review.

Zeolites are microporous tectosilicates of natural or synthetic origin, which have been extensively used in various technological applications, e.g. as catalysts and as molecular sieves, for separating and sorting various molecules, for water and air purification, including removal of radioactive contaminants, for harvesting waste heat and solar heat energy, for adsorption refrigeration, as detergents, etc. These applications of zeolites were typically related with their porous character, their high adsorption capacity, and their ion exchange properties. This review is focused on potential or already practically implemented applications of zeolites in biotechnology and medicine. Zeolites are promising for environment protection, detoxication of animal and human organisms, improvement of the nutrition status and immunity of farm animals, separation of various biomolecules and cells, construction of biosensors and detection of biomarkers of various diseases, controlled drug and gene delivery, radical scavenging, and particularly tissue engineering and biomaterial coating. As components of scaffolds for bone tissue engineering, zeolites can deliver oxygen to cells, can stimulate osteogenic cell differentiation, and can inhibit bone resorption. Zeolites can also act as oxygen reservoirs, and can improve cell performance in vascular and skin tissue engineering and wound healing. When deposited on metallic materials for bone implantation, zeolite films showed anticorrosion effects, and improved the osseointegration of these implants. In our studies, silicalite-1 films deposited on silicon or stainless steel substrates improved the adhesion, growth, viability and osteogenic differentiation of human osteoblast-like Saos-2 cells. Zeolites have been clinically used as components of haemostatics, e.g. in the Advanced Clotting Sponge, as gastroprotective drugs, e.g. Absorbatox® 2.4D, or as antioxidative agents (Klinobind®). Some zeolites are highly cytotoxic and carcinogenic, e.g. erionite. However, in other zeolites, the antiproliferative and pro-apoptotic effects can be used for tumor therapy.

Clinoptilolite for Treatment of Dyslipidemia: Preliminary Efficacy Study.

OBJECTIVES: A tribomechanically activated clinoptilolite (natural aluminosilicate mineral) has been used to increase growth in meat-producing animals, as an adjuvant in cancer therapy, and a heavy metal remover in humans. Because of its unique cation exchanging and chelating properties, we hypothesized that clinoptilolite may be beneficial for the treatment of dyslipidemia in the manner similar to bile acid sequestrants. Thus, specific aims of this pilot study were to orally administer clinoptilolite in different doses and granule size combinations to determine magnitude and time profile of changes in blood lipids. DESIGN: A phase I/IIa prospective, open-label, uncontrolled, dose/granule size-ranging study (treatment phase 8 weeks, follow-up 6 weeks). Blood lipids were examined every 2 weeks. SETTINGS: Outpatient clinic of a university-affiliated hospital. SUBJECTS: Forty-one subjects (all white, mean age 57.6 ± 6.8 years, 17 women) with blood lipids above the normative limits divided into three groups. INTERVENTION: A tribomechanically activated clinoptilolite was administered in three dose/grind combinations: 6 g/day of fine grind (6gF), 6 g/day of coarse grind (6gC), and 9 g/day of coarse grind (9gC). OUTCOME MEASURES: Blood concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglycerides (TG). RESULTS: For the 3 groups combined, all lipid fractions significantly improved after 8 weeks of treatment (20-25%, p < 0.001), which reversed to baseline after 6 weeks of clinoptilolite withdrawal. Early (week 2) and the most pronounced decrease in TC and LDLc was observed in the 6gF group (19% and 23% in week 8, respectively), with no difference in HDLc and TG between the three dose/grind groups. No side effects were reported. CONCLUSIONS: These pilot results suggest that oral administration of clinoptilolite may improve lipid profile in individuals with dyslipidemia, which warrants further investigations.

Nanozeolite bioconjugates labeled with 223Ra for targeted alpha therapy.

INTRODUCTION: Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters, 223Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α-particles, releasing 27.9MeV of cumulative energy. Unfortunately the lack of an appropriate bifunctional ligand for radium has so far been a main obstacle for the application of 223Ra in receptor targeted therapy. In our studies we investigated the use of nanozeolite-Substance P bioconjugates as vehicles for 223Ra radionuclides for targeted α therapy. METHODS: The sodium form of an A-type of nanozeolite (NaA) was synthesized using the template method. Next, the nanozeolite particles were conjugated to the Substance P (5-11) peptide fragment, which targets NK-1 receptors on glioma cells. The obtained bioconjugate was characterized by transmission emission spectroscopy, thermogravimetric analysis and dynamic light scattering analysis. The NaA-silane-PEG-SP(5-11) bioconjugates were labeled with 223Ra by exchange of the Na+ cation and the stability, receptor affinity and cytotoxicity of the obtained radiobioconjugates were tested. RESULTS: The 223Ra-labeled nanozeolite bioconjugate almost quantitatively retains 223Ra in vitro after 6days, while the retention of decay products varies from 90 to 95%. The synthesized 223RaA-silane-PEG-SP(5-11) showed high receptor affinity toward NK-1 receptor expressing glioma cells and exhibited a high cytotoxic effect in vitro. CONCLUSIONS: Substance P functionalized nanozeolite-A represents a viable solution for the use of the 223Ra in vivo generator as a therapeutic construct for targeting glioma cells.

ZEOLITE: "THE MAGIC STONE"; MAIN NUTRITIONAL, ENVIRONMENTAL, EXPERIMENTAL AND CLINICAL FIELDS OF APPLICATION.

INTRODUCTION: zeolites (clinoptilolites) are a family of alluminosilicates and cations clustered to form macro aggregates by small individual cavities. In the medical area they are involved in detoxification mechanisms capturing ions and molecules into their holes. Actually, we classify about 140 types of natural and 150 synthetic zeolites, for specific and selective use. Clinoptilolite is a natural zeolite and it is the most widespread compound in the medical market. OBJECTIVE: this review analyzes the main fields of zeolite utilization. METHODS: we searched Pubmed/Medline using the terms "zeolite" and "clinoptilolite". RESULTS AND DISCUSSION: in zoothechnology and veterinary medicine zeolite improves the pets' fitness, removes radioactive elements, aflatoxines and poisons. Zeolite displays also antioxidant, whitening, hemostatic and anti-diarrhoic properties, projected in human care. However very scanty clinical studies have been run up to now in immunodeficiency, oncology after chemotherapy and radiotherapy as adjuvants. CONCLUSIONS: further clinical investigations are urgently required after this review article publication which updates the state of the art.

Introducción: las zeolitas (clinoptilolitas) son una familia de aluminosilicatos y cationes agrupada para formar agregados macro de pequeñas cavidades individuales. En el área médica están involucrados en los mecanismos de desintoxicación y en capturar iones y moléculas en sus agujeros. En realidad, clasificamos cerca de 140 tipos de zeolitas naturales y 150 sintéticas, para usos específicos y selectivos. La clinoptilolita es una zeolita natural y es el compuesto más extendido en el mercado médico. Objetivo: esta revisión analiza los principales campos de utilización de la zeolita. Métodos: se realizaron búsquedas en Pubmed/Medline usando los términos "zeolita" y "clinoptilolita". Resultados y discusión: en zootecnología y medicina veterinaria la zeolita mejora la condición de la mascota, elimina los elementos radiactivos, las aflatoxinas y los venenos. En el cuidado humano, la zeolita también muestra propiedades antioxidantes, de blanqueamiento, homeostáticas y antidiarreicas. Sin embargo, los estudios clínicos que se han llevado a cabo hasta ahora como adyuvante en inmunodeficiencia y tras la quimioterapia y la radioterapia en oncología son muy escasos. Conclusiones: se requieren con urgencia otras investigaciones clínicas después de esta publicación del artículo que actualicen el estado de la técnica.

Effect of Clinoptilolite and Sepiolite Nanoclays on Human and Parasitic Highly Phagocytic Cells.

Nanoclays have potential applications in biomedicine raising the need to evaluate their toxicity in in vitro models as a first approach to its biocompatibility. In this study, in vitro toxicity of clinoptilolite and sepiolite nanoclays (NC) was analyzed in highly phagocytic cultures of amoebas and human and mice macrophages. While amebic viability was significantly affected only by sepiolite NC at concentrations higher than 0.1 mg/mL, the effect on macrophage cultures was dependent on the origin of the cells. Macrophages derived from human peripheral blood monocytes were less affected in viability (25% decrease at 48 h), followed by the RAW 264.7 cell line (40%), and finally, macrophages derived from mice bone marrow monocytes (98%). Moreover, the cell line and mice macrophages die mainly by necrosis, whereas human macrophages exhibit increased apoptosis. Cytokine expression analysis in media of sepiolite NC treated cultures showed a proinflammatory profile (INFγ, IL-1α, IL-8, and IL-6), in contrast with clinoptilolite NC that induced lees cytokines with concomitant production of IL-10. The results show that sepiolite NC is more toxic to amoebas and macrophages than clinoptilolite NC, mostly in a time and dose-dependent manner. However, the effect of sepiolite NC was comparable with talc powder suggesting that both NC have low cytotoxicity in vitro.

Faujasites incorporated tissue engineering scaffolds for wound healing: in vitro and in vivo analysis.

Exploring the possibility of using inorganic faujasites in tissue engineering scaffolds is a prospective approach in regenerative medicine. Novel gelatin/hyaluronic acid (HA)/faujasite porous scaffolds with low surface energy were fabricated by lyophilization. The pore size of gelatin/HA scaffold was 50-2000 µm, whereas it was greatly reduced to 10-250 µm after incorporation of 2.4% (w/w) of faujasites in polymer matrix, GH(2.4%). Micro computed tomography analysis showed that the porosity of GH(2.4%) was 90.6%. The summative effect was ideal for growth of dermal fibroblasts and cellular attachment. XRD analysis revealed that the embedded faujasites maintained their crystallinity in the polymer matrix even though they interacted with the polymers as indicated by FT-IR analysis. Coupling with effective reinforcement of faujasites, GH(2.4%) demonstrated compression modulus of 929 ± 7 Pa and glass transition temperature of 31 ± 0.05 °C. It exhibited controlled swelling and degradation, allowing sufficient space for tissue regrowth. The latter is further supported by capability of faujasites to provide efficient oxygen supply to fibroblast cells. GH(2.4%) showed a cell viability of 91 ± 8% on NIH 3T3 fibroblast cell lines. The in vivo studies on Sprague-Dawley rats revealed its ability to enhance wound healing by accelerating re-epithelization and collagen deposition. These findings indicated its potential as excellent wound dressing material.