Montmorillonite-norfloxacin nanocomposite intended for healing of infected wounds

The aim of this study was the design of a clay mineral-drug nanocomposite based on montmorillonite and norfloxacin (NF, antimicrobial drug) as a powder for cutaneous application, to enhance wound healing in infected skin lesions. The clay drug adsorption isotherm demonstrates that the mechanism of NF intercalation into montmorillonite galleries is the adsorption as one single process, due to the charge–charge interaction between protonated NF and negatively charged montmorillonite edges in the interlayer space. Nanocomposite is biocompatible and it is characterized by antimicrobial activity greater than the free drug: this is due to its nanostructure and controlled drug release properties. Considering the results obtained, NF–montmorillonite nanocomposite seems a promising tool to treat infected skin lesions or skin wounds prone to infection, as chronic ulcers (diabetic foot, venous leg ulcers) and burns

Zeolites as Ingredients of Medicinal Products

Development of new medicinal products for particular therapeutic treatment or for better manipulations with better quality and less side effects are possible as a result of advanced inorganic and organic materials application, among which zeolites, due to their properties and versatility, have been gaining attention. This paper is an overview of the development in the use of zeolite materials and their composites and modifications as medicinal products for several purposes such as active agents, carriers, for topical treatments, oral formulations, anticancer, the composition of theragnostic systems, vaccines, parenteral dosage forms, tissue engineering, etc. The objective of this review is to explore the main properties of zeolites and associate them with their drug interaction, mainly addressing the advances and studies related to the use of zeolites for different types of treatments due to their zeolite characteristics such as molecule storage capacity, physical and chemical stability, cation exchange capacity, and possibility of functionalization. The use of computational tools to predict the drug—zeolite interaction is also explored. As conclusion was possible to realize the possibilities and versatility of zeolite applications as being able to act in several aspects of medicinal products

Tablets of “Hydrochlorothiazide in Cyclodextrin in Nanoclay”: A New Nanohybrid System with Enhanced Dissolution Properties

Hydrochlorothiazide (HCT), a Biopharmaceutical Classification System (BCS) class IV drug, is characterized by low solubility and permeability, that negatively affect its oral bioavailability, reducing its therapeutic effcacy. The combined use of cyclodextrins (CDs) and nanoclays (NCs) recently proved to be a successful strategy in developing delivery systems able to merge the potential benefits of both carriers. In this work, several binary systems of CDs or NCs with the drug were obtained, using different drug:carrier ratios and preparation techniques, and characterized in solution and in solid state, to properly select the most effective system and preparation method. Then, the best CD (RAMEB) and NC (sepiolite), at the best drug:carrier ratio, was selected for preparation of the ternary system by co-evaporation and emerged as the most effective preparation method. The combined presence of RAMEB and sepiolite gave rise to a synergistic improvement of drug dissolution properties, with a two-fold increase in the amount of drug dissolved as compared with the corresponding HCT-RAMEB system, resulting in an approximately 12-fold increase in drug solubility as compared with the drug alone. The ternary system that was co-evaporated was then selected for a tablet formulation. The obtained tablets were fully characterized for technological properties and clearly revealed a better drug dissolution performance than the commercial reference tablet (Esidrex®)

Investigation into Brazilian Palygorskite for Its Potential Use as Pharmaceutical Excipient: Perspectives and Applications

Palygorskite is an aluminum and magnesium silicate characterized by its fibrous morphology, providing it with great versatility in industrial applications, including pharmaceuticals. Although most of the reserves are in the United States, in recent years occurrences of commercially exploited deposits in Brazil have been recorded, mainly in the country’s northeast region. This has motivated this study, which analyzes raw Brazilian palygorskite compared to a commercial sample (Pharmasorb® colloidal) to demonstrate its pharmaceutical potential. The chemical and mineral composition of the samples were evaluated for surface properties, granulometry, morphology, crystallography, thermal analysis, and spectroscopy. Raw palygorskite presented 67% purity, against 74% for Pharmasorb® colloidal. The percentage purity relates to the presence of contaminants, mainly carbonates and quartz (harmless under conventional conditions of pharmaceutical use). Furthermore, it was possible to confirm the chemical composition of these phyllosilicates, formed primarily of silicon, aluminum, and magnesium oxides. The crystallographic and spectroscopic profiles were consistent in both samples, showing characteristic peaks for palygorskite (2θ = 8.3°) and bands attributed to fibrous phyllosilicates below 1200 cm−1, respectively. The thermal analysis allowed the identification of the main events of palygorskite, with slight differences between the evaluated samples: loss of water adsorbed onto the surface (~85 °C), removal of water contained in the channels (~200 °C), coordinated water loss (~475 °C), and, finally, the dehydroxylation (>620 °C). The physicochemical characteristics of raw palygorskite align with pharmacopeial specifications, exhibiting a high specific surface area (122 m2/g), moderately negative charge (−13.1 mV), and compliance with the required limits for heavy metals and arsenic. These favorable technical attributes indicate promising prospects for its use as a pharmaceutical ingredient in the production of medicines and cosmetics.CAPES, grant number 88887.131333/2016-0

Hybrid Lipid/Clay Carrier Systems Containing Annatto Oil for Topical Formulations

Financial support for this research was provided by the Coordination of Improvement of Higher-Level Personnel-Brazil (CAPES)-02817/09. RMB and FNR acknowledge fellowships from National Council for Scientific and Technological Development CNPq (Brazil). This research also was financially supported by Junta de Andalucia, under the project reference PT18 RT 3786.Nanocomposites formed by clay and lipid carriers (NLCs) show a high potential for providing controlled release and specific delivery of bioactive molecules and have recently gained attention in the pharmaceutical sector due to their ability to transport hydrophilic and hydrophobic drugs. Recent studies have recognized the biological activity of the oil of Bixa orellana L. (AO) with regards to its healing, antioxidant, antibacterial, and anti-leishmanial properties. Therefore, the purpose of this study is the preparation and characterization of hybrid systems based on lipid nanocarriers and laponite for the delivery of AO. NLCs were prepared by the fusion-emulsification method, using cetyl palmitate (CP) or myristyl myristate (MM), AO, and Poloxamer 188. The morphology, hydrodynamic diameters, zeta potential (ZP), polydispersity index (PDI), thermal analysis, X-ray diffraction analysis (XRD), viscosity behavior, and cytotoxicity testing of the hybrid systems were performed. The thermal study and X-ray diffraction analyses (XRD) revealed polymorphic structural changes compatible with the amorphization of the material. Rheological assays highlighted a typical pseudoplastic behavior in all systems (MM and CP with LAP). The hybrid systems’ morphology, size diameters, and PDIs were similar, preset spherical and monodisperse structures ( 200 nm; <0.3), without significant change up to sixty days. The ZP values differed from each other, becoming higher with increasing AO concentration. XEDS spectra and elemental X-ray maps show peaks of lipids (organic components, C and O) and inorganic components O, Mg, and Si. All samples showed cell viability above 60%. The results indicated a stable, biocompatible hybrid system that can be an alternative for topical application.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) 02817/09Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)Junta de Andalucia PT18 RT 378

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting

In the last few years, attempts to improve the regeneration of damaged tendons have been rising due to the growing demand. However, current treatments to restore the original performance of the tissue focus on the usage of grafts; although, actual grafts are deficient because they often cannot provide enough support for tissue regeneration, leading to additional complications. The beneficial effect of combining 3D bioprinting and dECM as a novel bioink biomaterial has recently been described. Tendon dECMs have been obtained by using either chemical, biological, or/and physical treatments. Although decellularization protocols are not yet standardized, recently, different protocols have been published. New therapeutic approaches embrace the use of dECM in bioinks for 3D bioprinting, as it has shown promising results in mimicking the composition and the structure of the tissue. However, major obstacles include the poor structural integrity and slow gelation properties of dECM bioinks. Moreover, printing parameters such as speed and temperature have to be optimized for each dECM bioink. Here, we show that dECM bioink for 3D bioprinting provides a promising approach for tendon regeneration for future clinical applications.This work was funded by the University of the Basque Country UPV/EHU and the Basque Country Government (IT1448-22). Supported by the fellowships granted to Fouad Al-Hakim Khalak (PRE_2021_2_0181) and Sandra Ruiz-Alonso (PRE_2021_2_0153). Likewise, the authors thank ICTS “NANBIOSIS”, in particular the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), at the University of the Basque Country (UPV/EHU) in Vitoria-Gasteiz

Wound Healing Activity of Nanoclay/Spring Water Hydrogels

This project was supported by an FPU grant (MECD), the Spanish research group CTS-946 and the program for international mobility of PhD students (University of Granada). Special thanks to the Department of Drug Sciences of the University of Pavia (Italy).Background: hydrogels prepared with natural inorganic excipients and spring waters are commonly used in medical hydrology. Design of these clay-based formulations continues to be a field scarcely addressed. Safety and wound healing properties of different fibrous nanoclay/spring water hydrogels were addressed. Methods: in vitro biocompatibility, by means of MTT assay, and wound healing properties were studied. Confocal Laser Scanning Microscopy was used to study the morphology of fibroblasts during the wound healing process. Results: all the ingredients demonstrated to be biocompatible towards fibroblasts. Particularly, the formulation of nanoclays as hydrogels improved biocompatibility with respect to powder samples at the same concentration. Spring waters and hydrogels were even able to promote in vitro fibroblasts motility and, therefore, accelerate wound healing with respect to the control. Conclusion: fibrous nanoclay/spring water hydrogels proved to be skin-biocompatible and to possess a high potential as wound healing formulations. Moreover, these results open new prospects for these ingredients to be used in new therapeutic or cosmetic formulations.German Research Foundation (DFG)Spanish research group CTS-946Program for international mobility of PhD students (University of Granada

Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel–montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20–100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug–clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained.Ministerio de Ciencia e Innovacion government PCIN-2017-098 FIS2016-77692-C2-2-P CGL2016-80833-RJunta de Andalucia RNM1897 P18-RT-378

Carvacrol Prodrugs with Antimicrobial Activity Loaded on Clay Nanocomposites

Background: Carvacrol, an essential oil with antimicrobial activity against a wide range of pathogens, and its water soluble carvacrol prodrugs (WSCP1-3) were intercalated into montmorillonite (VHS) interlayers to improve their stability in physiological media and promote their absorption in the intestine. Methods: Intercalation of prodrugs by cation exchange with montmorillonite interlayer counterions was verified by X-ray powder diffraction and confirmed by Fourier transform infrared spectroscopy and thermal analysis. Results: In vitro release studies demonstrated that montmorillonite successfully controlled the release of the adsorbed prodrugs and promoted their bioactivation only in the intestinal tract where carvacrol could develop its maximum antimicrobial activity. The amount of WSCP1, WSCP2, and WSCP3 released from VHS were 38%, 54%, and 45% at acid pH in 120 min, and 65%, 78%, and 44% at pH 6.8 in 240 min, respectively. Conclusions: The resultant hybrids successfully controlled conversion of the prodrugs to carvacrol, avoiding premature degradation of the drug.Ministry of Education, Universities and Research (MIUR) FAR201

Wound Healing Activity of Nanoclay/Spring Water Hydrogels

Background: hydrogels prepared with natural inorganic excipients and spring waters are commonly used in medical hydrology. Design of these clay-based formulations continues to be a field scarcely addressed. Safety and wound healing properties of different fibrous nanoclay/spring water hydrogels were addressed. Methods: in vitro biocompatibility, by means of MTT assay, and wound healing properties were studied. Confocal Laser Scanning Microscopy was used to study the morphology of fibroblasts during the wound healing process. Results: all the ingredients demonstrated to be biocompatible towards fibroblasts. Particularly, the formulation of nanoclays as hydrogels improved biocompatibility with respect to powder samples at the same concentration. Spring waters and hydrogels were even able to promote in vitro fibroblasts motility and, therefore, accelerate wound healing with respect to the control. Conclusion: fibrous nanoclay/spring water hydrogels proved to be skin-biocompatible and to possess a high potential as wound healing formulations. Moreover, these results open new prospects for these ingredients to be used in new therapeutic or cosmetic formulations.This research was funded by Ministerio de Ciencia e Innovación, CGL2016–80833-R; Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía, P18-RT-3786 and Ministerio de Educación, Cultura y Deporte, FPU15/01577.Peer reviewe