Gel-forming Polymer Research Articles

Development, Optimization, and Evaluation of New Gel Formulations with Cyclodextrin Complexes and Volatile Oils with Antimicrobial Activity.

This study aimed to develop and evaluate hydrogels containing a cyclodextrin complex with clove essential oil and other free volatile oils with antimicrobial properties (tea tree and rosemary essential oils), focusing on their pharmaco-technical and rheological characteristics. The formulations varied in the Carbopol 940 (a hydrophilic polymer) and volatile oils' concentrations. Rheological analysis indicated that the gels displayed pseudoplastic behavior, with the flow index (n) values below 1, ensuring appropriate consistency and handling. The results showed that increasing the Carbopol concentration significantly enhanced the yield stress, consistency index, and viscosity, with gel B, containing 1% Carbopol, 1.5% tea tree essential oil, and 1.5% rosemary essential oil, demonstrating optimal stability and rheological properties. At the same time, the concentration of volatile oils was found to modulate the gels' flow parameters, but their effect was less pronounced than that of the gel-forming polymer. Antimicrobial testing revealed that both gel B and gel E (containing 1% Carbopol, 2% tea tree essential oil, and 2% rosemary essential oil) exhibited antimicrobial activity against Gram-positive, Gram-negative bacteria, and Candida spp., with gel E showing superior efficacy against Candida tropicalis. The antimicrobial effects were likely influenced by the higher concentrations of tea tree and rosemary essential oils in gel E. Overall, the study demonstrates that the concentration of Carbopol 940 primarily determines the gel's rheological behavior, while volatile oil concentration modulates antimicrobial effectiveness.

Design and Evaluation of New Gel-Based Floating Matrix Tablets Utilizing the Sublimation Technique for Gastroretentive Drug Delivery.

A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release.

Fluorescent Probes with Förster Resonance Energy Transfer Function for Monitoring the Gelation and Formation of Nanoparticles Based on Chitosan Copolymers.

Nanogel-forming polymers such as chitosan and alginic acid have a number of practical applications in the fields of drug delivery, food technology and agrotechnology as biocompatible, biodegradable polymers. Unlike bulk macrogel formation, which is followed by visually or easily detectable changes and physical parameters, such as viscosity or turbidity, the formation of nanogels is not followed by such changes and is therefore very difficult to track. The counterflow extrusion method (or analogues) enables gel nanoparticle formation for certain polymers, including chitosan and its derivatives. DLS or TEM, which are typically used for their characterization, only allow for the study of the already-formed nanoparticles. Alternatively, one might introduce a fluorescent dye into the gel-forming polymer, with the purpose of monitoring the effect of its microenvironment on the fluorescence spectra. But apparently, this approach does not provide a sufficiently specific signal, as the microenvironment may be affected by a big number of various factors (such as pH changes) including but not limited to gel formation per se. Here, we propose a new approach, based on the FRET effect, which we believe is much more specific and enables the elucidation of nanogel formation process in real time. Tryptophan-Pyrene is suggested as one of the donor-acceptor pairs, yielding the FRET effect when the two compounds are in close proximity to one another. We covalently attached Pyrene (the acceptor) to the chitosan (or PEG-chitosan) polymeric chain. The amount of introduced Pyrene was low enough to produce no significant effect on the properties of the resulting gel nanoparticles, but high enough to detect the FRET effect upon its interaction with Trp. When the Pyr-modified chitosan and Trp are both present in the solution, no FRET effect is observed. But as soon as the gel formation is initiated using the counterflow extrusion method, the FRET effect is easily detectable, manifested in a sharp increase in the fluorescence intensity of the pyrene acceptor and reflecting the gel formation process in real time. Apparently, the gel formation promotes the Trp-Pyr stacking interaction, which is deemed necessary for the FRET effect, and which does not occur in the solution. Further, we observed a similar FRET effect when the chitosan gel formation is a result of the covalent crosslinking of chitosan chains with genipin. Interestingly, using ovalbumin, having numerous Trp exposed on the protein surface instead of individual Trp yields a FRET effect similar to Trp. In all cases, we were able to detect the pH-, concentration- and temperature-dependent behaviors of the polymers as well as the kinetics of the gel formation for both nanogels and macrogels. These findings indicate a broad applicability of FRET-based analysis in biomedical practice, ranging from the optimization of gel formation to the encapsulation of therapeutic agents to food and biomedical technologies.

Development and in vitro assessment of Analgesic and Anti-inflammatory Mefenamic acid Nanosponge Loaded Topical Formulation

The present research work was done with the objective of topical formulation development of poorly water-soluble drug Mefenamic acid. The drug was firstly incorporated in nanosponge of ethyl cellulose. Then Mefenamic acid nanosponge-loaded topical gel formulations were developed by using Carbopol 934 as a gel-forming polymer. The Mefenamic acid-loaded nanosponges were tested for various quality parameters such as particle size distribution, polydispersity.index(PI),. Surface morphology and drug entrapment efficiency etc. Gel formulations were tested for viscosity, pH, in vitro diffusion and other parameters. The average size of developed nanosponge preparations was found between 250nm to 894nm. Scanning electron microscopy photographs of developed formulations clearly reveal the spongy and porous nature of particles along with spherical shape. The PI was. found in. the range. of 0.206 to 0.934. It was found that formulation N3 with a drug-to-polymer ratio of 1:4 has the highest drug loading. Further nanosponge were characterized for different parameters and results revealed acceptable characteristics of N3 formulation. These prepared nanosponges were loaded in topical Carbopol gel (Formulation G3) and evaluated for in vitro diffusion release. Obtained in vitro data was applied to numerous kinetic models which reveal typical zero order in vitro drug diffusion with prolonged release of Mefenamic acid and therefore it can be effectively used as analgesic and anti-inflammatory formulation.

Physical method of electret-thermal analysis

The article presents the data of electret-thermal analysis of ultrahigh molecular weight polyethylene as a polymer material promising for medicine and technology, polyvinyl alcohol as a biocompatible gel-forming polymer, blood as a system with coordinatively bound polarizable components, synovial fluid as a component of the lubricating medium of joints containing giauloronates and cholesterol esters, starch-containing polymer biodegradable compositions, chitosan as a natural electret biopolymer, vegetable oils as systems with supramolecular formations in the form of fatty acid triglyceride associates. The variants of interpretation of the thermally stimulated current spectra obtained during the analysis are proposed, which are based on the fundamental concepts of dielectric physics, condensed matter physics, and related natural science disciplines. It is concluded that the addition of the content of curricula in individual academic disciplines with information about this method will contribute to improving the effectiveness of specialists training by institutions of higher education.

Gel-Forming Soil Conditioners of Combined Action: Field Trials in Agriculture and Urban Landscaping.

The article summarizes multivariate field trials of gel-forming soil conditioners for agriculture and urban landscaping in various climatic conditions from arid (O.A.E., Uzbekistan) to humid (Moscow region, Russia). The field test program included environmental monitoring of weather data, temperature, water-air regimes, salinity, alkalinity, and biological activity of various soils (sandy and loamy sandy Arenosols, Retisols, loamy Serozems), productivity and yield of plants (lawns, vegetables) and their quality, including pathogen infestation. The evolutionary line of polymer superabsorbents from radiation-crosslinked polyacrylamide (1995) to the patented "Aquapastus" material (2014-2020) with amphiphilic fillers and biocidal additives demonstrated not only success, but also the main problems of using hydrogels in soils (biodegradation, osmotic collapse, etc.), as well as their technological solutions. Along with innovative materials, our know-how consisted in the intelligent soil design of capillary barriers for water accumulation and antipathogenic and antielectrolyte protection of the rhizosphere. Gel-forming polymer conditioners and new technologies of their application increase the productivity of plant crops and the quality of biomass by 30-50%, with a 1.3-2-fold saving of water resources and reliable protection of the topsoil from pathogens and secondary salinization. The results can be useful to a wide range of specialists from chemical technologists to agronomists and landscapers.

Microrheology of a thermosensitive gelling polymer for cell culture.

We investigate the rheo-mechanical properties of Mebiol Gel®, a thermosensitive gel-forming polymer extensively used as a medium for cellular culture, using passive microrheology made either by standard dynamic light scattering or by photon correlation imaging. In the dilute limit, Mebiol displays a Newtonian behavior with an effective viscosity that decreases with temperature, consistent with a peculiar aggregation mechanism characterized by an increase of the molecular weight with a simultaneous reduction of the aggregate size. By increasing concentration and approaching gelation, both the storage and loss moduli show a nonmonotonic dependence with temperature, with a pronounced maximum around Tm ≃ 28-30 °C, the value above which, in the dilute limit, the individual Mebiol chains are fully compacted. Such a distinctive trend of the elastic and viscous properties persists within the gel, which, therefore, becomes "softer" above Tm. Although when temperature changes are performed adiabatically, the transition from the fluid to the gel phase takes place without any apparent discontinuity, a rapid T-jump leads to the formation of a hard gel at a concentration where a low heating rate conversely yields a fluid phase. This is a visible manifestation of the nonequilibrium nature of these physical gels.

Study into the hydrolysis of polyhexamethylene guanidine hydrochloride

The development of new preparations for managing skin lesions is a task requiring a complex research approach. Thus, one promising direction consists in the creation of new bases for wound-healing drugs for external application. Chemical compounds that can be used as such bases include polymeric hydrogels, representing spatially cross-linked macromolecules that swell in a solvent. This property provides an opportunity to load hydrogels with drugs of both synthetic and herbal origin. A search for a gel-forming polymer acting not only as a drug carrier, but also as a healing agent presents a relevant research task. In a previous work, the authors obtained polyhexamethylene guanidine hydrochloride hydrogels by crosslinking terminal amino groups with formaldehyde. The conducted studies of the wound-healing capacity of the obtained hydrogels and compositions on their basis confirmed their comparability with such widely-used agents, as levomecol, bepanthene, etc. In addition, the obtained compositions were found to exhibit their own activity. Therefore, hydrogels based on polyhexamethylene guanidine hydrochloride can be used as a promising platform for drug design. In this work, the destruction products released during hydrolysis of the hydrogel under study were investigated. IR and UV spectroscopy methods were applied to evaluate the concentration of hydrogel destruction products over time. A mechanism of hydrogel destruction yielding the initial polyhexamethylene guanidine hydrochloride and formaldehyde in a gem-diol form is proposed.

FORMULATION AND EVALUATION OF NOVEL INSITU GEL SYSTEM IN THE MANAGEMENT OF RHEUMATOID ARTHRITIS

Objective: To develop in-situ gel formulations of Lornoxicam for sustained release to reduce the dosing frequency in the treatment of rheumatoid arthritis. Methods: The method of ion-sensitive in-situ gel formation was used in this study. Lornoxicam in situ gel formulations were prepared by varying concentrations of sodium alginate as a bio-degradable gel-forming polymer, CaCl2 as a cross-linking agent, and chitosan, HPMCK4, HPMCK15, guar gum, gellan gum, xanthan gum, pectin were used as drug release rate controlling polymers. The formulations F11-F18 were assessed for physical appearance, pH, in vitro drug release, viscosity, in vitro gelling capacity, and drug content. FTIR, DSC, and in vivo drug kinetics studies were conducted for lornoxicam pure drug and optimized formulation. Results: Formulations showed an optimum viscosity that will allow ease of administration and swallowing. All formulations were shown pH between 6.7 to 7.3, floating lag time was 2-3 sec and floated for 12 h. In vitro, drug release studies were reporting that commercial sustained release formulation of lornoxicam released 99.92% drug in 8 h, and optimized formulation F11 released 99.52% of the drug over a 12 h extended period. FTIR studies revealed no interaction between drugs and excipients used. The results of in vivo kinetic studies are approving the better performance of the optimized formulation. The Cmax, Tmax, t1/2, and AUC values are confirming the same thing. Conclusion: Lornoxicam oral in situ gel containing chitosan as a drug release controlling polymer is a promising approach for the treatment of rheumatoid arthritis in a convenient dosage form with better patient compliance and therapeutic response.

Formulation development, in vitro and in vivo assessment of Diclofenac diethylamine nanosponge loaded topical formulation

The present work was performed with the objective of novel topical formulation development of poorly water-soluble drug Diclofenac diethylamine by loading the drug-containing nanosponge into the topical formulation. The nanosponges are polymeric nanoparticles that entrap the drug. The drug-loaded nanosponge has different absorption characteristics in comparison to the pure drug in the topical drug delivery system. Methods: The drug was first loaded in the ethylcellulose nanosponge using the emulsion solvent diffusion method. Then Diclofenac diethylamine nanosponge-loaded topical gel formulations were developed by using Carbopol 940 as a gel-forming polymer. Result: The Diclofenac diethylamine-loaded nanosponges were evaluated for various evaluation parameters such as particle size distribution, surface morphology, drug entrapment efficiency, polydispersity index, etc. The topical gel formulations were evaluated for pH, in vitro drug release, viscosity, in vivo performance and compared with the marketed formulation. The average size of prepared nanosponge formulations was found in the range of 102.8 nm to 475.5 nm. Scanning electron microscopy photographs of developed formulations reveal the spongy and porous nature of particles along with spherical shape. The polydispersity index (PI) was found in the range of 0.756 to 0.954.

Evaluation of an Efficient and Skin-Adherent Semisolid Sunscreen Nanoformulation

Introduction: Sunscreens are substances applied on the skin surface to protect the skin from the harmful effects of UV light. Nanoparticles can increase the retention time of the sunscreen on the skin surface and its efficacy, by acting as physical barriers. The present investigation aimed to evaluate the influence of the chitosan coating of benzophenone-3-loaded lipid-core nanocapsules (CH-LCN) on the skin adhesion and photoprotective effect of the sunscreen. Methods: CH-LNC were obtained by the interfacial deposition of preformed polymer. A suitable semisolid formulation was obtained by using hydroxyethyl cellulose as the gel-forming polymer. Skin adhesion experiments were performed in vitro by applying the formulation on porcine skin and keeping it under water at 32 °C for up to 60 min. Photoprotective effect was analyzed in vitro by the capacity of the formulations to protect a photo unstable substance (resveratrol) from degradation under UV light. Results: CH-LNC presented size of around 150 nm, with low polydispersity, positive zeta potential, due to chitosan, and benzophenone-3 encapsulation efficiency of close to 100% (3 mg/mL). The proposed gel presented suitable consistence and pH for skin application and benzophenone-3 concentration of around 3 mg/g. Although coated and uncoated lipid-core nanocapsules increased benzophenone-3 skin adhesion after 10 min of water immersion, only the nanoparticles coated with chitosan were able to do so after 60 min. The chitosan coating of the nanocapsules increased the photoprotection of the sunscreen under UVA and UVB light after 60 min of exposure, probably due to the film-forming properties of chitosan. Conclusion: The chitosan coating of CH-LCN increased the skin adhesion and the photoprotective effect of the sunscreen.

Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose

Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water–ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol–water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1–4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

An individual alginate lyase is effective in the disruption of Laminaria digitata recalcitrant cell wall

In the present study, 199 pre-selected Carbohydrate-Active enZymes (CAZymes) and sulfatases were assessed, either alone or in combination, to evaluate their capacity to disrupt Laminaria digitata cell wall, with the consequent release of interesting nutritional compounds. A previously characterized individual alginate lyase, belonging to the family 7 of polysaccharide lyases (PL7) and produced by Saccharophagus degradans, was shown to be the most efficient in the in vitro degradation of L. digitata cell wall. The alginate lyase treatment, compared to the control, released up to 7.11 g/L of reducing sugars (p < 0.001) and 8.59 mmol/100 g dried alga of monosaccharides (p < 0.001), and reduced cell wall fluorescence intensity by 39.1% after staining with Calcofluor White (p = 0.001). The hydrolysis of gel-forming polymer alginate by the alginate lyase treatment could prevent the trapping of fatty acids and release beneficial monounsaturated fatty acids, particularly 18:1c9 (p < 0.001), to the extracellular medium. However, no liberation of proteins (p > 0.170) or pigments (p > 0.070) was observed. Overall, these results show the ability of an individual alginate lyase, from PL7 family, to partially degrade L. digitata cell wall under physiological conditions. Therefore, this CAZyme can potentially improve the bioavailability of L. digitata bioactive compounds for monogastric diets, with further application in feed industry.

Ibuprofen-Loaded Heparin Modified Thermosensitive Hydrogel for Inhibiting Excessive Inflammation and Promoting Wound Healing.

Hydrogels have been investigated as ideal biomaterials for wound treatment owing to their ability to form a highly moist environment which accelerates cell migration and tissue regeneration for prompt wound healing. They can also be used as a drug carrier for local delivery, and are able to activate immune cells to enhance wound healing. Here, we developed heparin-conjugated poly(N-isopropylacrylamide), an injectable, in situ gel-forming polymer, and evaluated its use in wound healing. Ibuprofen was encapsulated into the hydrogel to help reduce pain and excessive inflammation during healing. In addition to in vitro studies, a BALB/c mice model was used to evaluate its effect on would healing and the secretion of inflammatory mediators. The in vitro assay confirmed that the ibuprofen released from the hydrogel dramatically reduced lipopolysaccharide-induced inflammation by suppressing the production of NO, PGE2 and TNF-α in RAW264.7 macrophages. Moreover, an in vivo wound healing assay was conducted by applying hydrogels to wounds on the backs of mice. The results showed that the ibuprofen-loaded hydrogel improved healing relative to the phosphate buffered saline group. This study indicates that ibuprofen loaded in an injectable hydrogel is a promising candidate for wound healing therapy.

Multiscale Experimental Evaluation of Agarose-Based Semi-Interpenetrating Polymer Network Hydrogels as Materials with Tunable Rheological and Transport Performance.

This study introduces an original concept in the development of hydrogel materials for controlled release of charged organic compounds based on semi-interpenetrating polymer networks composed by an inert gel-forming polymer component and interpenetrating linear polyelectrolyte with specific binding affinity towards the carried active compound. As it is experimentally illustrated on the prototype hydrogels prepared from agarose interpenetrated by poly(styrene sulfonate) (PSS) and alginate (ALG), respectively, the main benefit brought by this concept is represented by the ability to tune the mechanical and transport performance of the material independently via manipulating the relative content of the two structural components. A unique analytical methodology is proposed to provide complex insight into composition–structure–performance relationships in the hydrogel material combining methods of analysis on the macroscopic scale, but also in the specific microcosms of the gel network. Rheological analysis has confirmed that the complex modulus of the gels can be adjusted in a wide range by the gelling component (agarose) with negligible effect of the interpenetrating component (PSS or ALG). On the other hand, the content of PSS as low as 0.01 wt.% of the gel resulted in a more than 10-fold decrease of diffusivity of model-charged organic solute (Rhodamine 6G).

Formulation, Characterization and Comparative Pharmacokinetic Study of Bupropion Floating Raft System as a Promising Approach for Treating Depression

The aim of this study was to formulate, evaluate, and compare satiety-enhancing floating raft system (FRS) of bupropion as gastroretentive drug delivery systems (GRDDS) using in-situ gelling pectin and alginate. Bupropion was considered as a good candidate for such systems due to high water solubility that requires frequent dosing. Pectin and alginate could prolong satiety sensation augmenting weight loss of bupropion. A 24 full factorial design was tailored to inspect the effect of the response variables (gel-forming polymer type, calcium carbonate percentage, glyceride lipid type and percentage). Gelation lag time, floating lag time, as well as drug released percent after 1 and 8 h were selected as dependent variables. The optimal system was investigated for compatibility and bioavailability study in healthy human volunteers relative to marketed Wellbutrin® sustained release tablets. The optimal FRS (3% alginate, 2% precirol®, and 2% CaCO3) was selected. This system had an optimum viscosity that will allow a rapid sol-gel transformation in the stomach, excellent floating behavior, and controlled release profile with a comparable bioavailability. The optimal FRS would be a novel liquid GRDDS in controlling bupropion rate release especially for depression associated with eating disorders or dysphagia improving patient compliance and drug efficacy.

Preparation and Structural Characterization of Complex Oxide Eutectic Precursors from Polymer-Salt Xerogels Obtained by Microwave-Assisted Drying.

Sol–gel synthesis is an acknowledged method for obtaining fine inorganic powders of a different nature. Implementation of water-soluble polymers as gel-forming media makes this technique even more readily available, especially in cases where conventional gel formation is suppressed. In polymer–salt solutions, polymers serve as scaffolds for salt constituents’ bulk crystallization. When dried, solid salt particles are deposited on the polymer surface or in polymer matrix pores, which leads to higher grain size uniformity. The present work discusses the effect of drying conditions on phase composition and structure characteristics of complex oxide eutectics in ternary systems, CaO–Al2O3–Y2O3 (CAY) and MgO–Al2O3–Y2O3 (MAY), obtained from polymer–salt compositions based on polyvinyl alcohol (PVA), Na-salt of carboxymethylcellulose (Na-CMC) or polyvinylpyrrolidone (PVP). Microwave-assisted drying proved to be more efficient compared to convective process; however such technique requires careful selection of gel-forming polymer.

Converting nanosuspension into inhalable and redispersible nanoparticles by combined in-situ thermal gelation and spray drying

While nanoparticulate drugs for deep lung delivery hold promise for particular disease treatments, their size-related physical instability and tendency of being exhaled during breathing remain major challenges to their inhaled formulation development. Here we report a viable method for converting drug nanosuspensions into inhalable, stable and redispersible nano-agglomerates through combined in-situ thermal gelation and spray drying. Itraconazole (ITZ) nanosuspensions were prepared by flash nanoprecipitation, and co-spray dried with two different grades of the gel-forming polymer, methylcellulose (MC M20 and MC M450) as protectants. MC M20 was found superior in protecting ITZ nanoparticles against thermal stress (through nanoparticle entrapment within its gel network structure) during spray drying. In terms of redispersibility, an Sf/Si ratio (i.e., ratio of nanoparticle sizes after and before spray drying) of unity (1.02 ± 0.03), reflecting full particle size preservation, was achieved by optimizing the suspending medium content and spray drying parameters. Formulation components, nanosuspension concentration and spray drying parameters all showed a significant impact on the aerosol performance of the resulting agglomerates, but an absence of defined trends or correlations. Overall, the MC-protected nano-agglomerates displayed excellent in-vitro aerosol performance with fine particle fractions higher than 50% and mass median aerodynamic diameters within the 2–3 µm range, which are ideal for deep lung delivery.

Poly(Vinyl Alcohol) Cryogels Formed from Polymer Solutions in Dimethyl Sulfoxide with Tetramethoxysilane Additives

Organic–inorganic hybrid cryogels of poly(vinyl alcohol) (PVA) containing silica inclusions (SiO2) were obtained and studied. Such inclusions were formed in the course of hydrolytic polycondensation (sol-gel process) of tetramethoxysilane (TMOS) introduced into concentrated polymer solutions in dimethyl sulfoxide (DMSO). PVA concentration in these solutions was 60, 80 or 100 g/L; while the concentration of TMOS was varied in a range of 0.15–0.61 mol/L. The polymer solutions were subjected to the cryogenic treatment at temperatures by 40 °С lower than DMSO crystallization temperature (+18.4°C). The frozen samples were thawed out at a heating rate of 0.03°/min. It is shown that moderate freezing at −21.6 °C, then frozen storage and subsequent thawing of the initial reaction mixture PVA/DMSO/TMOS/acid catalyst resulted in the formation of strong macroporous PVA/SiO2 cryogels. Such cryogel materials are hybrid systems, because the gel-forming polymer and the silica containing moieties belong to the content of the gel phase. The basis of this intermolecular interaction is hydrogen bonding between OH groups of the adjacent chains. This leads to the formation of modified microcrystallinity zones that perform as the nodes of the three-dimensional network of cryogels. The effects of significant increase in their rigidity and heat-resistance with increasing PVA and TMOS concentration in the initial feed were also observed. It was shown that the success of the synthesis of transparent elastic and heat-resistant PVA/SiO2 cryogels depends on the choice of the optimal ratio between the precursors and the combined effect of the liquid (methanol and water) and silicon-containing components on the formation of multiple hydrogen bonds and microcrystallites.

The Combined Effects of Co-Culture and Substrate Mechanics on 3D Tumor Spheroid Formation within Microgels Prepared via Flow-Focusing Microfluidic Fabrication.

Tumor spheroids are considered a valuable three dimensional (3D) tissue model to study various aspects of tumor physiology for biomedical applications such as tissue engineering and drug screening as well as basic scientific endeavors, as several cell types can efficiently form spheroids by themselves in both suspension and adherent cell cultures. However, it is more desirable to utilize a 3D scaffold with tunable properties to create more physiologically relevant tumor spheroids as well as optimize their formation. In this study, bioactive spherical microgels supporting 3D cell culture are fabricated by a flow-focusing microfluidic device. Uniform-sized aqueous droplets of gel precursor solution dispersed with cells generated by the microfluidic device are photocrosslinked to fabricate cell-laden microgels. Their mechanical properties are controlled by the concentration of gel-forming polymer. Using breast adenocarcinoma cells, MCF-7, the effect of mechanical properties of microgels on their proliferation and the eventual spheroid formation was explored. Furthermore, the tumor cells are co-cultured with macrophages of fibroblasts, which are known to play a prominent role in tumor physiology, within the microgels to explore their role in spheroid formation. Taken together, the results from this study provide the design strategy for creating tumor spheroids utilizing mechanically-tunable microgels as 3D cell culture platform.