Gellan gum-based in situ gelling ophthalmic nanosuspension of Posaconazole.
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ABSTRACT:
SUBMITTER: Khare P
PROVIDER: S-EPMC9089292 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Adipose tissue is involved in many physiological processes. Therefore, the need for adipose tissue-like analogues either for soft tissue reconstruction or as in vitro testing platforms is undeniable. In this work, we explored the natural features of gellan gum (GG) to recreate injectable stable adipose-like microtissues. GG hydrogel particles with different percentages of polymer (0.5%, 0.75%, 1.25%) were developed and the effect of obtained mechanical properties over the ability of hASCs to differentiate towards the adipogenic lineage was evaluated based on the expression of the early (PPARγ) and late (FABP4) adipogenic markers, and on lipids formation and accumulation. Constructs were cultured in adipogenic induction medium up to 21 days or for six days in induction plus nine days in maintenance media. Overall, no significant differences were observed in terms of hASCs adipogenic differentiation within the range of Young’s moduli between 2.7 and 12.9 kPa. The long-term (up to six weeks) stability of the developed constructs supported its application in soft tissue reconstruction. Moreover, their ability to function as adipose-like microtissue models for drug screening was demonstrated by confirming its sensitivity to TNFα and ROCK inhibitor, respectively involved in the repression and induction of the adipogenic differentiation.
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Project description:Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)-based spongy-like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin-resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic-associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA-infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration.
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Project description:Gellan Gum (GG) has been recently proposed for tissue engineering applications. GG hydrogels are produced by physical crosslinking methods induced by temperature variation or by the presence of divalent cations. However, physical crosslinking methods may yield hydrogels that become weaker in physiological conditions due to the exchange of divalent cations by monovalent ones. Hence, this work presents a new class of GG hydrogels crosslinkable by both physical and chemical mechanisms. Methacrylate groups were incorporated in the GG chain, leading to the production of a methacrylated Gellan Gum (MeGG) hydrogel with highly tunable physical and mechanical properties. The chemical modification was confirmed by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR-ATR). The mechanical properties of the developed hydrogel networks, with Young's modulus values between 0.15 and 148 kPa, showed to be tuned by the different crosslinking mechanisms used. The in vitro swelling kinetics and hydrolytic degradation rate were dependent on the crosslinking mechanisms used to form the hydrogels. Three-dimensional (3D) encapsulation of NIH-3T3 fibroblast cells in MeGG networks demonstrated in vitro biocompatibility confirmed by high cell survival. Given the highly tunable mechanical and degradation properties of MeGG, it may be applicable for a wide range of tissue engineering approaches.
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Project description:Chitosan (CHT) based polyelectrolyte complexes (PECs) have been receiving great attention for tissue engineering approaches. These hydrogels are held together by ionic forces and can be disrupted by changes in physiological conditions. In this study, we present a new class of CHT-based PEC hydrogels amenable to stabilization by chemical crosslinking. The photocrosslinkable anionic methacrylated gellan gum (MeGG) was complexed with cationic CHT and exposed to light, forming a PEC hydrogel. The chemical characterization of the photocrosslinkable PEC hydrogel by Fourier transform infrared spectroscopy (FTIR) revealed absorption peaks specific to the raw polymers. A significantly higher swelling ratio was observed for the PEC hydrogel with higher CHT content. The molecular interactions between both polysaccharides were evaluated chemically and microscopically, indicating the diffusion of CHT to the interior of the hydrogel. We hypothesized that the addition of MeGG to CHT solution first leads to a membrane formation around MeGG. Then, migration of CHT inside the MeGG hydrogel occurs to balance the electrostatic charges. The photocrosslinkable feature of MeGG further allowed the formation of cell-laden microscale hydrogel units with different shapes and sizes. Overall, this system is potentially useful for a variety of applications including the replication of microscale features of tissues for modular tissue engineering.
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Project description:The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of gellan gum (E 418) as a food additive. Following the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available. Based on the reported use levels, a refined exposure of up to 72.4 mg/kg body weight (bw) per day in toddlers at the 95th percentile was estimated. Gellan gum is unlikely to be absorbed intact and would not be fermented by human intestinal microbiota. There is no concern with respect to carcinogenicity and genotoxicity. No adverse effects were reported in chronic studies at the highest doses tested in mice and rats (3,627 and 1,460 mg gellan gum/kg bw per day, respectively). Repeated oral intake up to 200 mg/kg bw per day for 3 weeks had no adverse effects in humans. The Panel concluded that there is no need for a numerical acceptable daily intake (ADI) for gellan gum (E 418), and that there is no safety concern at the refined exposure assessment for the reported uses and use levels of gellan gum (E 418) as a food additive. The Panel recommended to better define the specifications of gellan gum including the absence of viable cells of the microbial source and the presence of polyhydroxybutyrate (PHB), protein and residual bacterial enzymatic activities.
| S-EPMC7009714 | biostudies-literature
Project description:This study targets the synthesis of novel semi-interpenetrating networks and amphiphilic conetworks, where hydrophilic soft matter (Gellan Gum, GG) was combined with hydrophobic rigid poly(styrene), PSt. To achieve that, GG was chemically modified with 4-vinyl benzyl chloride to form a reactive macromonomer with multiple double bonds. These double bonds were used in a copolymerization with styrene to initially form semi-interpenetrating networks (SIPNs) where linear PSt was intertwined within the GG-PSt conetwork. The interpenetrating linear PSt and unreacted styrene were extracted over 3 consecutive days with yields 18-24%. After the extraction, the resulting conetworks (yields 76-82%) were able to swell both in organic and aqueous media. Thermo-mechanical tests (thermal gravimetric analysis, differential scanning calorimetry, and dynamic mechanical analysis) and rheology indicated that both SIPNs and conteworks had, in most cases, improved thermal and mechanical properties compared to pure poly(styrene) and pure GG gels. This crosslinking strategy proved that the reactive combination of a synthetic polymer and a bio-derived constituent would result in the formation of more sustainable materials with improved thermo-mechanical properties. The binding ability of the amphiphilic conetworks towards several organic dyes was high, showing that they could be used as potential materials in environmental clean-up.
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Project description:This work contains original data supporting our research paper "Antibacterial effectiveness meets improved mechanical properties: Manuka Honey/Gellan Gum composite hydrogels for cartilage repair", Bonifacio et al., in press [1], in which innovative composite hydrogels, based on Gellan Gum/Manuka honey/Halloysite nanotubes were described as biomaterials for cartilage regeneration. Here the composites were further examined by means of Fourier Transform Infrared Spectroscopy, in Attenuated Total Reflectance mode (FT-IR/ATR). Materials devoted to cartilage replacement must possess adequate fluid permeability and lubricating capability, therefore, a deeper investigation on water uptake kinetics of freeze-dried specimens up to 21 days in PBS was carried out. Moreover, since the degradation rate of a biomaterial plays a pivotal role in tissue engineering, weight loss measurements of the prepared hydrogels were performed in simulated synovial fluid, in phosphate buffer solution (PBS) and in lysozyme. Scanning Electron Microscopy images provide insight into the morphology of the freeze-dried samples. Finally, additional information on Staphylococcus aureus and Staphylococcus epidermidis ability to adhere onto the prepared hydrogel composites in short times were obtained, as well as the chondrogenic potential of the composites assessed by SDS-PAGE followed by Coomassie blue gel staining.
| S-EPMC6134162 | biostudies-literature
Project description:Gellan gum (GG) spongy-like hydrogels have been explored for different tissue engineering (TE) applications owing to their highly attractive hydrogel-like features, and improved mechanical resilience and cell performance. Although the whole process for the preparation of these materials is well-defined, we hypothesized that variations occurring during the freezing step lead to batch-to-batch discrepancies. Aiming to address this issue, two freezing devices were tested, to prepare GG spongy-like hydrogels in a more reproducible way. The cooling and freezing rates, the nucleation time and temperature, and the end freezing time were determined at different freezing temperatures (-20, -80, and -210 °C). The efficacy of the devices was assessed by analyzing the physicochemical, mechanical, and biological properties of different formulations. The cooling rate and freezing rate varied between 0.1 and 128 °C/min, depending on the temperature used and the device. The properties of spongy-like hydrogels prepared with the tested devices showed lower standard deviation in comparison to those prepared with the standard process, due to the slower freezing rate of the hydrogels. However, with this method, mean pore size was significantly lower than that with the standard method. Cell entrapment, adhesion, and viability were not affected as demonstrated with human dermal fibroblasts. This work confirmed that batch-to-batch variations are mostly due to the freezing step and that the tested devices allow fine tuning of the scaffolds' structure and properties.
| S-EPMC7077413 | biostudies-literature
Project description:Gellan gum (GG) was chemically modified with methacrylic moieties to produce a photocrosslinkable biomaterial ink, hereinafter called methacrylated GG (GGMA), with improved physico-chemical properties, mechanical behavior and stability under physiological conditions. Afterwards, GGMA was functionalized by incorporating two different bioactive compounds, a naturally derived eumelanin extracted from the black soldier fly (BSF-Eumel), or hydroxyapatite nanoparticles (HAp), synthesized by the sol-gel method. Different ink formulations based on GGMA (2 and 4% (w/v)), BSF-Eumel, at a selected concentration (0.3125 mg/mL), or HAp (10 and 30% wHAp/wGGMA) were developed and processed by three-dimensional (3D) printing. All the functionalized GGMA-based ink formulations allowed obtaining 3D-printed GGMA-based scaffolds with a well-organized structure. For both bioactive signals, the scaffolds with the highest GGMA concentration (4% (w/v)) and the highest percentage of infill (45%) showed the best performances in terms of morphological and mechanical properties. Indeed, these scaffolds showed a good structural integrity over 28 days. Given the presence of negatively charged groups along the eumelanin backbone, scaffolds consisting of GGMA/BSF-Eumel demonstrated a higher stability. From a mechanical point of view, GGMA/BSF-Eumel scaffolds exhibited values of storage modulus similar to those of GGMA ones, while the inclusion of HAp at 30% (wHAp/wGGMA) led to a storage modulus of 32.5 kPa, 3.5-fold greater than neat GGMA. In vitro studies proved the capability of the bioactivated 3D-printed scaffolds to support 7F2 osteoblast cell growth and differentiation. BSF-Eumel and HAp triggered a different time-dependent physiological response in the osteoblasts. Specifically, while the ink with BSF-Eumel acted as a stimulus towards cell proliferation, reaching the highest value at 14 days, a higher expression of alkaline phosphatase activity was detected for scaffolds consisting of GGMA and HAp. The overall findings demonstrated the possible use of these biomaterial inks for 3D-printed bone tissue-engineered scaffolds.
| S-EPMC9963483 | biostudies-literature
Project description:Microgel particles have emerged in the past few years as a favorite model system for fundamental science and for innovative applications ranging from the industrial to biomedical fields. Despite their potentialities, no works so far have focused on the application of microgels for cultural heritage preservation. Here we show their first use for this purpose, focusing on wet paper cleaning. Exploiting their retentive properties, microgels are able to clean paper, ensuring more controlled water release from the gel matrix, in analogy to their macroscopic counterpart, i.e., hydrogels. However, differently from these, the reduced size of microgels makes them suitable to efficiently penetrate in the porous structure of the paper and to easily adapt to the irregular surfaces of the artifacts. To test their cleaning abilities, we prepare microgels made of Gellan gum, a natural and widespread material already used as a hydrogel for paper cleaning, and apply them to modern and ancient paper samples. Combining several diagnostic methods, we show that microgels performances in the removal of cellulose degradation byproducts for ancient samples are superior to commonly employed hydrogels and water bath treatments. This is due to the composition and morphology of ancient paper, which facilitates microgels penetration. For modern paper cleaning, performances are at least comparable to the other methods. In all cases, the application of microgels takes place on a time scale of a few minutes, opening the way for widespread use as a rapid and efficient cleaning protocol.
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