Physicochemical and rheological characterization of different low molecular weight gellan gum products and derived ionotropic crosslinked hydrogels

A series of four different low molecular weight gellan gum products was obtained by alkaline hydrolysis with the aim to investigate the impact of the molecular weight on the rheological properties of the polysaccharide aqueous dispersions and on the physicochemical characteristics of derived ionotropic crosslinked hydrogels. In particular, thermo-rheological analysis was conducted on aqueous dispersions to study the influence of molecular weight on the thermogelation properties typical of the native polysaccharide while strain sweep experiments were conducted to establish if aqueous dispersion shows a viscoelastic behavior. The effect of different Ca2+ on the rheological properties of hydrogels were studied. Furthermore, ionotropic crosslinked hydrogels were analyzed in terms of morphology on the dried state and swelling behavior, while their viscoelastic properties were studied by means of rheological analysis conducted in frequency sweep regime after different time points of incubation in phosphate buffer at pH 7.4. Release experiments conducted using fluorescein isothiocyanate labelled dextran as a model diffusion agent and was performed to investigate the possibility of using the low molecular weight GG-derived hydrogels as an active molecule-releasing device. Finally, the cytocompatibility of hydrolysis products was investigated, as well as the capacity of hydrogels to encapsulate viable MC3T3-E1 preosteoblastic cells

HYALURONIC ACID DERIVATIVE MICELLES AS OCULAR PLATFORMS TO DRUG RELEASE AND CORNEAL PERMEATION

In traditional ocular formulations, only small amount of the administered drug penetrates the cornea to reach the intraocular tissue. One approach to improve the drug ocular bioavailability was to develop colloidal drug delivery systems. Polymeric micelles seem to be very promising for their capacity to dissolve a variety of hydrophobic drugs by enhancing their water solubility and so their bioavailability. They are able to increase ocular drug permeability due to interact with the complex corneal structure. Considering the advantages to use mucoadhesive polymer to increase drug residence time on the ocular surface, the aim of this work was to prepare hyaluronic acid-based micelles as a platform to release corticosteroids on the ocular surface. Three amphiphilic derivatives of hyaluronic acid (HA), bearing different amount of hexadecylamine chains (C16), were synthesised and characterized. These are able to form micelles by using the co-solvent evaporation method. All HAC16 derivatives have shown the ability of durable mucoadhesive interactions and resulted potentially useful for corticosteroids encapsulation. Drug-loaded micelles were prepared and characterized in term of drug loading amount and particle size. Moreover, the in vitro drug release studies from micellar systems were carried out in comparison with the dissolution profile of the free drug suspension. Cytocompatibility studies also were performed with HCEpiC cells. HAC16b (DDC16mol%=12%) micelles are selected as the best nanosystems, and their capacity to improve the drugs permeability across corneal barrier are evaluated. Thus, the ex vivo permeation studies were conducted using bovine corneas and Franz type diffusion cells

Hyaluronic-Based Antibacterial Hydrogel Coating for Implantable Biomaterials in Orthopedics and Trauma: From Basic Research to Clinical Applications

Bacterial colonization of implanted biomaterials remains one of the most challenging complications in orthopedics and trauma surgery, with extremely high social and economic costs. Antibacterial coating of implants has been advocated by many experts as a possible solution to reduce the burden of implant-related infection and several different solutions have been proposed in the last decades. However, while most of the investigated technologies have shown their efficacy in vitro and/or in vivo, only few were able to reach the market, due to clinical, industrial, economic and regulatory issues. Hyaluronic acid composites have been previously shown to possess antifouling capabilities and have been used in various clinical settings to reduce bacterial adhesion and mitigate biofilm-related infections. Recently, a fast-resorbable, hyaluronic-based hydrogel coating was developed to protect implanted biomaterials in orthopedics, trauma and maxillofacial surgery. Preclinical and clinical testing did show the safety and efficacy of the device that can be intraoperatively loaded with one or more antibiotics and directly applied by the surgeon to the implant surface, at the time of surgery. Here, we review the current evidence concerning this very first antibacterial coating of implants and outline the economic impact of the possible large-scale application of this technology

Chapter Hyaluronic-Based Antibacterial Hydrogel Coating for Implantable Biomaterials in Orthopedics and Trauma: From Basic Research to Clinical Applications

Bacterial colonization of implanted biomaterials remains one of the most challenging complications in orthopedics and trauma surgery, with extremely high social and economic costs. Antibacterial coating of implants has been advocated by many experts as a possible solution to reduce the burden of implant-related infection and several different solutions have been proposed in the last decades. However, while most of the investigated technologies have shown their efficacy in vitro and/or in vivo, only few were able to reach the market, due to clinical, industrial, economic and regulatory issues. Hyaluronic acid composites have been previously shown to possess antifouling capabilities and have been used in various clinical settings to reduce bacterial adhesion and mitigate biofilm-related infections. Recently, a fast-resorbable, hyaluronic-based hydrogel coating was developed to protect implanted biomaterials in orthopedics, trauma and maxillofacial surgery. Preclinical and clinical testing did show the safety and efficacy of the device that can be intraoperatively loaded with one or more antibiotics and directly applied by the surgeon to the implant surface, at the time of surgery. Here, we review the current evidence concerning this very first antibacterial coating of implants and outline the economic impact of the possible large-scale application of this technology

Modulation of physical and biological properties of a composite PLLA and polyaspartamide derivative obtained via thermally induced phase separation (TIPS) technique

In the present study, blend of poly l-lactic acid (PLLA) with a graft copolymer based on α,β-poly(N-hydroxyethyl)-dl-aspartamide and PLA named PHEA-PLA, has been used to design porous scaffold by using Thermally Induced Phase Separation (TIPS) technique. Starting from a homogeneous ternary solution of polymers, dioxane and deionised water, PLLA/PHEA-PLA porous foams have been produced by varying the polymers concentration and de-mixing temperature in metastable region. Results have shown that scaffolds prepared with a polymer concentration of 4% and de-mixing temperature of 22.5 °C are the best among those assessed, due to their optimal pore size and interconnection. SEM and DSC analysis have been carried out respectively to study scaffold morphology and the influence of PHEA-PLA on PLLA crystallization, while DMF extraction has been carried out in order to quantify PHEA-PLA into the final scaffolds. To evaluate scaffold biodegradability, a hydrolysis study has been performed until 56 days by incubating systems in a media mimicking physiological environment (pH 7.4). Results obtained have highlighted a progressive increase in weight loss with time in PLLA/PHEA-PLA scaffolds, conceivably due to the presence of PHEA-PLA and polymers interpenetration. Viability and adhesion of bovine chondrocytes seeded on the scaffolds have been studied by MTS test and SEM analysis. From results achieved it appears that the presence of PHEA-PLA increases cells affinity, allowing a faster adhesion and proliferation inside the scaffold

FLASH radiotherapy with electrons: issues related to the production, monitoring, and dosimetric characterization of the beam

Various in vivo experimental works carried out on different animals and organs have shown that it is possible to reduce the damage caused to healthy tissue still preserving the therapeutic efficacy on the tumor tissue, by drastically reducing the total time of dose delivery (<200 ms). This effect, called the FLASH effect, immediately attracted considerable attention within the radiotherapy community, due to the possibility of widening the therapeutic window and treating effectively tumors which appear radioresistant to conventional techniques. Despite the experimental evidence, the radiobiological mechanisms underlying the FLASH effect and the beam parameters contributing to its optimization are not yet known in details. In order to fully understand the FLASH effect, it might be worthy to investigate some alternatives which can further improve the tools adopted so far, in terms of both linac technology and dosimetric systems. This work investigates the problems and solutions concerning the realization of an electron accelerator dedicated to FLASH therapy and optimized for in vivo experiments. Moreover, the work discusses the saturation problems of the most common radiotherapy dosimeters when used in the very high dose-per-pulse FLASH conditions and provides some preliminary experimental data on their behavior