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Background and Aims: Submucosal injection agents are widely used solutions in gastric polyp resection techniques. Currently, many different solutions are used in clinical practice, but most are not authorised for this use or are not biopharmaceutical characterised. The objective of this multidisciplinary work is to test the efficacy of a novel thermosensitive hydrogel designed specifically for this indication., Methods: A mixture design of various components (Pluronic®, hyaluronic acid and sodium alginate) was carried out to select the combination with optimal properties for this use. Three final thermosensitive hydrogels were selected on which biopharmaceutical characterisation was performed and stability and biocompatibility were analysed. Efficacy in maintaining elevation was tested ex vivo on pig mucosa and in vivo in pigs RESULTS: The mixture design allowed selection of the ideal combinations of agents for the characteristics sought. The thermosensitive hydrogels studied showed high values of hardness and viscosity at 37 °C, maintaining good syringeability. One of them demonstrated superiority in maintaining polyp elevation in the ex vivo assay and non-inferiority in the in vivo assay., Conclusion: The thermosensitive hydrogel specifically designed for this use is promising both for its biopharmaceutical characteristics and for its demonstrated efficacy. This study lays the foundation for evaluating the hydrogel in humans., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anxo Fernandez Ferreiro reports financial support was provided by Axencia Galega de Innovación. Anxo Fernandez Ferreiro reports financial support was provided by Carlos III Health Institute., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest α-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-α-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hen's egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-α-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Cystinosis is a rare autosomal recessive disorder in which cystine crystals accumulate within the lysosomes of various organs, including the cornea. Ocular treatment is based on the administration of cysteamine eye drops, requiring its instillation several times per day. We have introduced the cysteamine in two types of previously developed ocular hydrogels (ion sensitive hydrogel with the polymers gellan gum and kappa-carrageenan and another one composed of hyaluronic acid), aiming at increasing the ocular retention in order to extend the dosing interval. The biopermanence studies (direct measurements and PET/CT) show that these formulations present a high retention time on the ocular surface of rats. From the in vitro release study we determined that both hydrogels can control the release of cysteamine over time, showing a zero order kinetics during four hours. At the same time, these hydrogels could act as corneal absorption promoters, as they allow a higher permeation of cysteamine through bovine cornea compared to a solution. HET-CAM test and cytotoxicity assays show no irritation on the ocular surface. These results demonstrate that the developed formulations present a high potential as vehicles for the topical ocular administration of cysteamine., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Physical hydrogels have been designed for a double purpose: as growth factor delivery systems and as scaffolds to support cell colonization and formation of new bone. Specifically, the polysaccharide gellan gum and the ubiquitous endogenous molecules chondroitin, albumin and spermidine have been used as exclusive components of these hydrogels. The mild ionotropic gelation technique was used to preserve the bioactivity of the selected growth factor, rhBMP-2. In vitro tests demonstrated the effective delivery of rhBMP-2 in its bioactive form. In vivo experiments performed in the muscle tissue of Wistar rats provided a proof of concept of the ability of the developed platforms to elicit new bone formation. Furthermore, this biological effect was better than that of a commercial formulation currently used for regenerative purposes, confirming the potential of these hydrogels as new and innovative growth factor delivery platforms and scaffolds for regenerative medicine applications., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well-established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99m Tc-DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one-phase decay and a half time of 262min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chitosan and gelatin are biodegradable and biocompatible polymers which may be used in the preparation of 3D scaffolds with applications in biomedicine. Chitosan/gelatin scaffolds crosslinked with glutaraldehyde were prepared by ice segregation induced self-assembly (ISISA); a unidirectional freezing at -196°C followed freeze-drying to produce macroporous materials with a well-patterned structure. This process may be included within the green chemistry by the preparation of the porous structures without using organic solvents, moreover is a versatile, non-difficult and cheap process. The scaffolds prepared by ISISA were characterized by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, thermal gravimetric analysis, differential scanning calorimetry, and their stability was evaluated by degree swelling and degradation tests. The scaffolds present properties as high porosity, high degree swelling and good stability which make them suitable of applications as biomaterials., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in the absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of gellan gum and 20% kappa-carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6h., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The clinical application of sparingly soluble drugs is hampered by the wide range of problems associated to their delivery. Herein we present a new physical hydrogel as a delivery system for these drugs. The strategy behind the design of this delivery system involved the incorporation of the protein albumin into the hydrogel with the aim of exploiting its intrinsic capacity to bind small hydrophobic molecules. Prednisolone and ketoconazole were used as model drug molecules. A combination of the saturation transfer difference (STD) spectra and a novel double titration assay followed by NMR was applied to study all of the possible binding modes between albumin and each drug. Finally, the ability of the hydrogel system to release the two model drugs was corroborated. The results of the release studies were in agreement with the drug binding capacities derived from the NMR studies, thus confirming that the potential of the NMR approach as a predictive technique could be useful in evaluating the designs of new drug delivery systems., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Endogen polyamines are known to be molecules of high biological value. Herein, a new generation of physical hydrogels was developed through the mild ionotropic gelantion technique, using the endogen polyamine spermidine as a physical cross-linker. The main negatively charged polymer of the hydrogel is the natural polysaccharide gellan gum. Optionally, interesting endogen molecules, such as chondroitin sulfate and albumin, can be included as part of the formulation. These new hydrogels were characterized and the influence of the different components on their final properties was carefully analyzed, ultimately demonstrating the possibility to modulate these properties as well as the system's versatility in terms of composition. On the contrary, in vitro cell studies showed the absence of cytotoxicity of these hydrogels. Finally, the in vitro-release profiles obtained for different model molecules evidenced the potential of these systems as novel drug delivery platforms., (Copyright © 2013 Wiley Periodicals, Inc.)