Thermosensitive Poly(DHSe/PEG/PPG Urethane)-Based Hydrogel Extended Remdesivir Application in Ophthalmic Medication

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.

In-Situ Ocular Gel Pharmaceutical Delivery System: A Recent Review

Ocular Drug Delivery has been a key challenge and attractive field for the pharmaceutical scientist due to peerless anatomy and physiology of eye. Glaucoma, dry eye syndrome, keratitis, endophthalmitis, trachoma, and conjunctivitis are just a few of the conditions that can affect the eye. In order to accomplish efficient ocular treatment within the eye, At the point of action, an appropriate supply of active substances must be given and sustained. Due to fast precorneal medication loss, traditional treatment has a low bioavailability. The bioavailability of a medicine is also influenced by static and dynamic barriers. To address the limitations of traditional treatment, significant efforts are being made to develop innovative medication systems for ocular delivery. When a drop is injected into the eye, it goes through a sol-gel transition and forms a cul-de-sac. The in-situ gel system, which comprises thermally triggered, pH triggered, and ion cross linking systems, is the subject of this review. It includes a step-by-step procedure for preparing the pH-triggered system as well as assessment parameters. Keywords: Conventional dosage form, Anatomy and physiology in eye, In-situ gel.

New Physical Hydrogels Based on Co−Assembling of FMOC−Amino Acids

In the last years, physical hydrogels have been widely studied due to the characteristics of these structures, respectively the non−covalent interactions and the absence of other necessary components for the cross−linking processes. Low molecular weight gelators are a class of small molecules which form higher ordered structures through hydrogen bonding and π−π interactions. In this context it is known that the formation of hydrogels based on FMOC−amino acids is determined by the primary structures of amino acids and the secondary structure arrangement (alpha−helix or beta−sheet motifs). The present study aimed to obtain supramolecular gels through co−assembly phenomenon using FMOC−amino acids as low molecular weight gelators. The stability of the new structures was evaluated by the vial inversion test, while FTIR spectra put into evidence the interaction between the compounds. The gel−like structure is evidenced by viscoelastic parameters in oscillatory shear conditions. SEM microscopy was used to obtain the visual insight into the morphology of the physical hydrogel network while DLS measurements highlighted the sol−gel transition. The molecular arrangement of gels was determined by circular dichroism, fluorescence and UV–Vis spectroscopy.

Desiccation-induced fibrous condensation of CAHS protein from an anhydrobiotic tardigrade

Anhydrobiosis, one of the most extensively studied forms of cryptobiosis, is induced in certain organisms as a response to desiccation. Anhydrobiotic species has been hypothesized to produce substances that can protect their biological components and/or cell membranes without water. In extremotolerant tardigrades, highly hydrophilic and heat-soluble protein families, cytosolic abundant heat-soluble (CAHS) proteins, have been identified, which are postulated to be integral parts of the tardigrades’ response to desiccation. In this study, to elucidate these protein functions, we performed in vitro and in vivo characterizations of the reversible self-assembling property of CAHS1 protein, a major isoform of CAHS proteins from Ramazzottius varieornatus, using a series of spectroscopic and microscopic techniques. We found that CAHS1 proteins homo-oligomerized via the C-terminal α-helical region and formed a hydrogel as their concentration increased. We also demonstrated that the overexpressed CAHS1 proteins formed condensates under desiccation-mimicking conditions. These data strongly suggested that, upon drying, the CAHS1 proteins form oligomers and eventually underwent sol–gel transition in tardigrade cytosols. Thus, it is proposed that the CAHS1 proteins form the cytosolic fibrous condensates, which presumably have variable mechanisms for the desiccation tolerance of tardigrades. These findings provide insights into molecular strategies of organisms to adapt to extreme environments.

Making and Breaking of Gels: Stimuli-Responsive Properties of Bis(Pyridyl-N-oxide Urea) Gelators

The structural modification of existing supramolecular architecture is an efficient strategy to design and synthesize supramolecular gels with tunable and predictable properties. In this work, we have modified bis(pyridyl urea) compounds with different linkers, namely hexylene and butylene, to their corresponding bis(pyridyl-N-oxide urea). The gelation properties of both the parent and the modified compounds were studied, and the results indicated that modification of the 3-pyridyl moieties to the corresponding 3-pyridyl-N-oxides induced hydrogelation. The stability of the parent and modified compounds were evaluated by sol-gel transition temperature (Tgel) and rheological measurements, and single-crystal X-ray diffraction was used to analyze the solid-state interactions of the gelators. The morphologies of the dried gels were analyzed by scanning electron microscopy (SEM), which revealed that the structural modification did not induce any prominent effect on the gel morphology. The stimuli-responsive behavior of these gels in the presence of salts in DMSO/water was evaluated by rheological experiments, which indicated that the modified compounds displayed enhanced gel strength in most cases. However, the gel network collapsed in the presence of the chloride salts of aluminum(III), zinc(II), copper(II), and cadmium(II). The mechanical strength of the parent gels decreased in the presence of salts, indicating that the structural modification resulted in robust gels in most cases. The modified compounds formed gels below minimum gel concentration in the presence of various salts, indicating salt-induced gelation. These results show the making and breaking ability of the gel network in the presence of external stimuli (salts), which explains the potential of using LMWGs based on N-oxide moieties as stimuli-responsive materials.

Acidic and Heat Processing of Egg Yolk Dispersions

Egg yolk is a multifunctional ingredient widely used in many food products, wherein proteins are the dominant component contributing to this functionality. However, the potential risk of foodborne illness associated with egg use forces us to ensure that foodstuffs based on egg yolk are managed in a safe and sanitary manner. Lowering the pH under a certain value by adding acids could serve this purpose, but it can also greatly modify the rheological and functional properties of egg yolk. This research aims to assess the influence of citric acid on the rheological properties and microstructure of chicken egg yolk dispersions and their heat-set gels. The dispersions were prepared from fresh hen’s eggs yolks by adding water or citric acid to obtain a technical yolk (45 wt.% in solids) at the desired pH value. Viscoelastic measurements were carried out using a control stress rheometer, and microstructure was evaluated by cryo-scanning electronic microscopy (CryoSEM). An evolution of the viscoelastic properties of egg yolk dispersions from fluid to gel behavior was observed as the pH decreased until 2 but showing a predominantly fluid behavior at pH 3. The profile of viscoelastic properties along the thermal cycle applied is modified to a great extent, also showing a strong dependence on pH. Thus, the sol–gel transition can be modulated by the pH value.

Preparation and Characterization of Salt-Mediated Injectable Thermosensitive Chitosan/Pectin Hydrogels for Cell Embedding and Culturing

In recent years, growing attention has been directed to the development of 3D in vitro tissue models for the study of the physiopathological mechanisms behind organ functioning and diseases. Hydrogels, acting as 3D supporting architectures, allow cells to organize spatially more closely to what they physiologically experience in vivo. In this scenario, natural polymer hybrid hydrogels display marked biocompatibility and versatility, representing valid biomaterials for 3D in vitro studies. Here, thermosensitive injectable hydrogels constituted by chitosan and pectin were designed. We exploited the feature of chitosan to thermally undergo sol–gel transition upon the addition of salts, forming a compound that incorporates pectin into a semi-interpenetrating polymer network (semi-IPN). Three salt solutions were tested, namely, beta-glycerophosphate (βGP), phosphate buffer (PB) and sodium hydrogen carbonate (SHC). The hydrogel formulations (i) were injectable at room temperature, (ii) gelled at 37 °C and (iii) presented a physiological pH, suitable for cell encapsulation. Hydrogels were stable in culture conditions, were able to retain a high water amount and displayed an open and highly interconnected porosity and suitable mechanical properties, with Young’s modulus values in the range of soft biological tissues. The developed chitosan/pectin system can be successfully used as a 3D in vitro platform for studying tissue physiopathology.