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Drosophila glue, a bioadhesive produced by fly larvae to attach themselves to a substrate for several days, has recently gained attention for its peculiar adhesive and mechanical properties. Although Drosophila glue production was described more than 50 years ago, a general survey of the adhesive and mechanical properties of this proteinaceous gel across Drosophila species is lacking. To measure adhesion, we present here a protocol that is robust to variations in protocol parameters, pupal age and calculation methods. We find that the glue, which covers the entire pupal surface, increases the animal rigidity and plasticity when bound to a glass slide. Our survey of pupal adhesion in 25 Drosophilidae species reveals a wide range of phenotypes, from species that produce no or little glue and adhere little, to species that produce high amounts of glue and adhere strongly. One species, D. hydei, stands out from the rest and emerges as a promising model for the development of future bioadhesives, as it has the highest detachment force per glue area and produces relatively large amounts of glue relative to its size. We also observe that species that invest more in glue tend to live in more windy and less rainy climates, suggesting that differences in pupal adhesion properties across species are shaped by ecological factors. Our present survey provides a basis for future biomimetic studies based on Drosophila glue. [ABSTRACT FROM AUTHOR]

Abstract Drosophila glue, a bioadhesive produced by fly larvae to attach themselves to a substrate for several days, has recently gained attention for its peculiar adhesive and mechanical properties. Although Drosophila glue production was described more than 50 years ago, a general survey of the adhesive and mechanical properties of this proteinaceous gel across Drosophila species is lacking. To measure adhesion, we present here a protocol that is robust to variations in protocol parameters, pupal age and calculation methods. We find that the glue, which covers the entire pupal surface, increases the animal rigidity and plasticity when bound to a glass slide. Our survey of pupal adhesion in 25 Drosophilidae species reveals a wide range of phenotypes, from species that produce no or little glue and adhere little, to species that produce high amounts of glue and adhere strongly. One species, D. hydei, stands out from the rest and emerges as a promising model for the development of future bioadhesives, as it has the highest detachment force per glue area and produces relatively large amounts of glue relative to its size. We also observe that species that invest more in glue tend to live in more windy and less rainy climates, suggesting that differences in pupal adhesion properties across species are shaped by ecological factors. Our present survey provides a basis for future biomimetic studies based on Drosophila glue.

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze–thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV–Vis methods. The hydrogel's morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel's ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications. [ABSTRACT FROM AUTHOR]

3D bioprinting techniques have enabled the fabrication of irregular large‐sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)‐gelatin‐dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs. [ABSTRACT FROM AUTHOR]

Xerosis is one of the common dermatological problems. Preparations recommended for daily care of the dry skin are emollients. Emollient preparations demonstrate a moisturizing effect, they soften and smoothen the skin, keep water in the epidermis, supplement lipids of skin upper layers and protect from external harmful agents. The purpose of this study was to develop and characterize emollients containing natural emulsifier Olivem 1000 as topical delivery systems for urea or sodium hialuronate. Physicochemical and mechanical properties of designed formulations were evaluated. Moreover, ex vivo adhesion study on the hairless mice skin as a model of adhesive layer was carried out and in vivo preliminary assessment of transepidermal water loss (TEWL) was performed. Prepared emollient formulations were characterized by smooth consistency, they were easily spreadable on the skin surface and showed no phase separation. Formulations containing xanthan gum as a thickening agent were characterized by higher viscosity, hardness, cohesiveness and adhesiveness values. Prepared emollients showed thixotropic properties and they were classified as non-Newtonian shear thinning systems. All prepared emollients demonstrated bioadhesive properties. The analysis of TEWL showed that the greatest decrease in the TEWL value was noted in the case of emollient containing sodium hyaluronate which was applied to the person with the skin described as “the skin in a very poor condition”. The results of the conducted research indicate that developed emollients containing natural emulsifier Olivem 1000 seem to be a promising form of care preparations for topical use in case of chronic dryness of the skin.

Drug administration by oral delivery is the preferred route, regardless of some remaining challenges, such as short resident time and toxicity issues. One strategy to overcome these barriers is utilizing mucoadhesive vectors that can increase intestinal resident time and systemic uptake. In this study, biomimetic nanoparticles (NPs) were produced from 14 types of edible algae and evaluated for usage as oral DDSs by measuring their size, surface charge, morphology, encapsulation efficiency, mucoadhesion force, and cellular uptake into Caco-2 cells. The NPs composed of algal materials (aNPs) exhibited a spherical morphology with a size range of 126–606 nm and a surface charge of −9 to −38 mV. The mucoadhesive forces tested ex vivo against mice, pigs, and sheep intestines revealed significant variation between algae and animal models. Notably, Arthospira platensis (i.e., Spirulina) NPs (126 ± 2 nm, −38 ± 3 mV) consistently exhibited the highest mucoadhesive forces (up to 3127 ± 272 µN/mm²). Moreover, a correlation was found between high mucoadhesive force and high cellular uptake into Caco-2 cells, further supporting the potential of aNPs by indicating their ability to facilitate drug absorption into the human intestinal epithelium. The results presented herein serve as a proof of concept for the possibility of aNPs as oral drug delivery vehicles. [ABSTRACT FROM AUTHOR]

Known as the degenerative disease of the knee with the highest prevalence, knee osteoarthritis (KOA) is characterized by a gradual destructive mechanism that, in severe cases, can provoke the need for total knee substitution. As the disease progresses, various enzymatic, immunological, and inflammatory processes abnormally degrade hyaluronic acid (HA), SF's main component, and affect the concentrations of specific proteins, with the final results seriously endangering synovial fluid (SF)'s rheological and tribological features and characteristics. No effective treatments have been found to stop the progression of KOA, but the injection of HA-based viscoelastic gels has been considered (alone or combined with physiotherapy (PT)) as an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the characteristics of SF, SF aspirated from groups treated for KOA (HA Kombihylan® and groups that received Kombihylan® and complex PT) was analyzed and compared from analytical, spectrophotometrical, and rheological perspectives. In the patients treated with PT, the SF extracted 6 weeks after viscosupplementation had a superior elastic modulus (G′) and viscous moduli (G″), as well as a homogeneous distribution of proteins and polysaccharides. The viscosupplementation fluid improved the bioadhesive properties of the SF, and the use of the viscosupplementation fluid in conjunction with PT was found to be favorable for the distribution of macromolecules and phospholipids, contributing to the lubrication process and the treatment of OA-affected joints. [ABSTRACT FROM AUTHOR]

Abstract 3D bioprinting techniques have enabled the fabrication of irregular large‐sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)‐gelatin‐dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs.

Xerosis is one of the common dermatological problems. Preparations recommended for daily care of dry skin are emollients. Emollient preparations demonstrate a moisturizing effect, they soften and smoothen the skin, keep water in the epidermis, supplement lipids of skin upper layers, and protect from external harmful agents. The purpose of this study was to develop and characterize emollients containing natural emulsifier Olivem 1000 as topical delivery systems for urea or sodium hyaluronate. The physicochemical and mechanical properties of the designed formulations were evaluated. Moreover, an ex vivo adhesion study on hairless murine skin as a model of adhesive layer was conducted and an in vivo preliminary assessment of transepidermal water loss (TEWL) was performed. The prepared emollient formulations were characterized by a smooth consistency, were easily spreadable on the skin surface, and showed no phase separation. Formulations containing xanthan gum as a thickening agent were characterized by higher viscosity, hardness, cohesiveness and adhesiveness values. The prepared emollients showed thixotropic properties and were classified as non-Newtonian shear thinning systems. All prepared emollients demonstrated bioadhesive properties. The TEWL analysis showed that the greatest decrease in the TEWL value was noted in the case of an emollient containing sodium hyaluronate, which was applied to a person with skin described as in very poor condition. The results of the conducted research indicate that the developed emollients containing natural emulsifier Olivem 1000 seem to be a promising form of care preparations for topical use in the case of chronic skin dryness. [ABSTRACT FROM AUTHOR]

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze–thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV–Vis methods. The hydrogel’s morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel’s ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications.

Summary: Biofilm‐forming benthic diatoms are key primary producers in coastal habitats, where they frequently dominate sunlit intertidal substrata. The development of gliding motility in raphid diatoms was a key molecular adaptation that contributed to their evolutionary success. However, the structure–function correlation between diatom adhesives utilized for gliding and their relationship to the extracellular matrix that constitutes the diatom biofilm is unknown.Here, we have used proteomics, immunolocalization, comparative genomics, phylogenetics and structural homology analysis to investigate the evolutionary history and function of diatom adhesive proteins.Our study identified eight proteins from the adhesive trails of Craspedostauros australis, of which four form a new protein family called Trailins that contain an enigmatic Choice‐of‐Anchor A (CAA) domain, which was acquired through horizontal gene transfer from bacteria. Notably, the CAA‐domain shares a striking structural similarity with one of the most widespread domains found in ice‐binding proteins (IPR021884).Our work offers new insights into the molecular basis for diatom biofilm formation, shedding light on the function and evolution of diatom adhesive proteins. This discovery suggests that there is a transition in the composition of biomolecules required for initial surface colonization and those utilized for 3D biofilm matrix formation. [ABSTRACT FROM AUTHOR]

Hydrogels are homogeneous three-dimensional polymeric networks capable of holding large amounts of water and are widely used in topical formulations. Herein, the physicomechanical, rheological, bioadhesive, and drug-release properties of hydrogels containing hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were examined, and the intermolecular interactions between the polymers were explored. A three-level factorial design was used to form HPMC–PVP binary hydrogels. The physicomechanical properties of the binary hydrogels alongside the homopolymeric HPMC hydrogels were characterized using a texture analyzer. Rheological properties of the gels were studied using a cone and plate rheometer. The bioadhesiveness of selected binary hydrogels was tested on porcine skin. Hydrophilic benzophenone-4 was loaded into both homopolymeric and binary gels, and drug-release profiles were investigated over 24 h at 33 °C. Fourier transform infrared spectroscopy (FTIR) was used to understand the inter-molecular drug–gel interactions. Factorial design analysis supported the dominant role of the HPMC in determining the gel properties, rather than the PVP, with the effect of both polymer concentrations being non-linear. The addition of PVP to the HPMC gels improved adhesiveness without significantly affecting other properties such as hardness, shear-thinning feature, and viscosity, thereby improving bioadhesiveness for sustained skin retention without negatively impacting cosmetic acceptability or ease of use. The release of benzophenone-4 in the HPMC hydrogels followed zero-order kinetics, with benzophenone-4 release being significantly retarded by the presence of PVP, likely due to intermolecular interactions between the drug and the PVP polymer, as confirmed by the FTIR. The HPMC–PVP binary hydrogels demonstrate strong bioadhesiveness resulting from the addition of PVP with desirable shear-thinning properties that allow the formulation to have extended skin-retention times. The developed HPMC–PVP binary hydrogel is a promising sustained-release platform for topical drug delivery. [ABSTRACT FROM AUTHOR]

Hazelnut shells, the main waste deriving from hazelnut processing, represent an interesting source of active molecules useful in pharmaceutics, although they have not yet been examined in depth. A hydrosoluble extract (hazelnut shell extract, HSE) was prepared by the maceration method using a hydroalcoholic solution and used as the active ingredient of patches (prepared by casting method) consisting of composites of highly deacetylated chitosan and green clay. In vitro studies showed that the formulation containing HSE is able to stimulate keratinocyte growth, which is useful for healing purposes, and to inhibit the growth of S. aureus (Log CFU/mL 0.95 vs. 8.85 of the control after 48 h); this bacterium is often responsible for wound infections and is difficult to treat by conventional antibiotics due to its antibiotic resistance. The produced patches showed suitable tensile properties that are necessary to withstand mechanical stress during both the removal from the packaging and application. The obtained results suggest that the developed patch could be a suitable product to treat wounds. [ABSTRACT FROM AUTHOR]

Drug administration by oral delivery is the preferred route, regardless of some remaining challenges, such as short resident time and toxicity issues. One strategy to overcome these barriers is utilizing mucoadhesive vectors that can increase intestinal resident time and systemic uptake. In this study, biomimetic nanoparticles (NPs) were produced from 14 types of edible algae and evaluated for usage as oral DDSs by measuring their size, surface charge, morphology, encapsulation efficiency, mucoadhesion force, and cellular uptake into Caco-2 cells. The NPs composed of algal materials (aNPs) exhibited a spherical morphology with a size range of 126–606 nm and a surface charge of −9 to −38 mV. The mucoadhesive forces tested ex vivo against mice, pigs, and sheep intestines revealed significant variation between algae and animal models. Notably, Arthospira platensis (i.e., Spirulina) NPs (126 ± 2 nm, −38 ± 3 mV) consistently exhibited the highest mucoadhesive forces (up to 3127 ± 272 µN/mm²). Moreover, a correlation was found between high mucoadhesive force and high cellular uptake into Caco-2 cells, further supporting the potential of aNPs by indicating their ability to facilitate drug absorption into the human intestinal epithelium. The results presented herein serve as a proof of concept for the possibility of aNPs as oral drug delivery vehicles.

Known as the degenerative disease of the knee with the highest prevalence, knee osteoarthritis (KOA) is characterized by a gradual destructive mechanism that, in severe cases, can provoke the need for total knee substitution. As the disease progresses, various enzymatic, immunological, and inflammatory processes abnormally degrade hyaluronic acid (HA), SF’s main component, and affect the concentrations of specific proteins, with the final results seriously endangering synovial fluid (SF)’s rheological and tribological features and characteristics. No effective treatments have been found to stop the progression of KOA, but the injection of HA-based viscoelastic gels has been considered (alone or combined with physiotherapy (PT)) as an alternative to symptomatic therapies. In order to evaluate the effect of viscosupplementation and PT on the characteristics of SF, SF aspirated from groups treated for KOA (HA Kombihylan® and groups that received Kombihylan® and complex PT) was analyzed and compared from analytical, spectrophotometrical, and rheological perspectives. In the patients treated with PT, the SF extracted 6 weeks after viscosupplementation had a superior elastic modulus (G′) and viscous moduli (G″), as well as a homogeneous distribution of proteins and polysaccharides. The viscosupplementation fluid improved the bioadhesive properties of the SF, and the use of the viscosupplementation fluid in conjunction with PT was found to be favorable for the distribution of macromolecules and phospholipids, contributing to the lubrication process and the treatment of OA-affected joints.

The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 μm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect (p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis. [ABSTRACT FROM AUTHOR]

Phytoplankton and diatom microalgae species cause biofouling by adhering to the surfaces, especially in closed cultivation systems such as tubular photobioreactors. This biofilm formation blocks the sunlight; after harvesting, it is necessary to clean the reactor. This cleaning process causes loss not only for time and finance but also in terms of environmental pollution due to using toxic chemicals and excess water usage. This study aimed to investigate the reduction of the microorganism cell adhesion on the hybrid surface. To succeed in this, the composite surface of tetraethoxysilane (TEOS) and lactic acid (LA) was prepared by the sol-gel process. Then the hybrid surfaces were coated on glass slides by the dip coating method. The wettability performance of the TEOS-LA hybrid surface was investigated using contact angle measurement and light transmittance. The wettability result showed that the superhydrophilic surface having 54 mJ/m2 of surface free energy values was obtained. An increase in the lactic acid content of the composite films increased the surface free energy (SFE) values decreasing the water contact angle. A pencil hardness test characterized the mechanical strength of the surfaces, and it was determined that the hardness of the composite films was decreased by increasing the LA content of the composite films. Resultantly, it is found that the TEOS-LA superhydrophilic composite film reduces the adhesion of microalgae.

Skin inflammation is a symptom of many skin diseases, such as eczema, psoriasis, and dermatitis, which cause rashes, redness, heat, or blistering. The use of natural products with anti-inflammatory properties has gained importance in treating these symptoms. Ursolic acid (UA), a promising natural compound that is used to treat skin diseases, exhibits low aqueous solubility, resulting in poor absorption and low bioavailability. Designing topical formulations focuses on providing adequate delivery via application to the skin surface. The aim of this study was to formulate and characterize lipid-surfactant-based systems for the delivery of UA. Microemulsions and liquid crystalline systems (LCs) were characterized by polarized light microscopy (PLM), rheology techniques, and textural and bioadhesive assays. PLM supported the self-assembly of these systems and elucidated their formation. Rheologic examination revealed pseudoplastic and thixotropic behavior appropriate, and assays confirmed the ability of these formulations to adhere to the skin. In vivo studies were performed, and inflammation induced by croton oil was assessed for response to microemulsions and LCs. UA anti-inflammatory activities of ~60% and 50% were demonstrated by two microemulsions and 40% and 35% by two LCs, respectively. These data support the continued development of colloidal systems to deliver UA to ameliorate skin inflammation. [ABSTRACT FROM AUTHOR]

Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a satisfying outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface receptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-β/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds. Diabetic chronic wound is among the serious complications of diabetes that eventually cause the amputation of limbs. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and EGCG was constructed. The EGCG not only acted as a carrier but also possessed a therapeutic effect of ROS scavenging. The AE-NPs enhanced the binding activity of aFGF to cell surface receptors on the cell surface, which improved the stability of aFGF in hostile conditions. Moreover, AE-NPs significantly accelerated wound healing and improved collagen remodeling by regulating the TGF-β/Smad signaling pathway. Our results bring new insights into the field of polyphenol-containing nanoparticles, showing their potential as drug delivery systems of macromolecules to treat diabetic wounds. [Display omitted] [ABSTRACT FROM AUTHOR]

Bacterial colonization occurs on all biological and artificial surfaces in the oral cavity. The formation of multicellular biofilms or settlement of misallocated species can cause caries (diet‐depending acidification), periodontal diseases, peri‐implantitis, or denture‐associated stomatitis. Inhibition or delay of initial adhesion should strongly reduce dental interventions. However, no strategy is found to mildly manage bacterial colonization in this complex physiological environment, that is, without toxic, antibacterial, or antiseptic approaches. It is shown in a previous study that micro‐ and submicrometer surface topographies, which can effectively control initial bacterial adhesion in other application areas, do not have any significant impact within the oral cavity. Herein, a simple approach is presented to reduce initial microbial surface colonization by plain biphasic textures with defined combinations of hydrophobic and hydrophilic phases (SiO2, NH2, CH2, CH3, F3). A significant reduction of microbial adhesion on textures in the nano‐ and microscale (150 nm and 2.4 μm) compared to respective monophasic substrates is observed. This might be a new design principle for dental materials, to inhibit microbial colonization in critical scenarios, at least for shorter time scales (

The extracellular matrix (ECM), an integral component of all organs, is inherently tissue adhesive and plays a pivotal role in tissue regeneration and remodeling. However, man-made three-dimensional (3D) biomaterials that are designed to mimic ECMs do not intrinsically adhere to moisture-rich environments and often lack an open macroporous architecture required for facilitating cellularization and integration with the host tissue post-implantation. Furthermore, most of these constructs usually entail invasive surgeries and potentially a risk of infection. To address these challenges, we recently engineered biomimetic and macroporous cryogel scaffolds that are syringe injectable while exhibiting unique physical properties, including strong bioadhesive properties to tissues and organs. These biomimetic catechol-containing cryogels were prepared from naturally-derived polymers such as gelatin and hyaluronic acid and were functionalized with mussel-inspired dopamine (DOPA) to impart bioadhesive properties. We found that using glutathione as an antioxidant and incorporating DOPA into cryogels via a PEG spacer arm led to the highest tissue adhesion and improved physical properties overall, whereas DOPA-free cryogels were weakly tissue adhesive. As shown by qualitative and quantitative adhesion tests, DOPA-containing cryogels were able to adhere strongly to several animal tissues and organs such as the heart, small intestine, lung, kidney, and skin. Furthermore, these unoxidized (i.e., browning-free) and bioadhesive cryogels showed negligible cytotoxicity toward murine fibroblasts and prevented the ex vivo activation of primary bone marrow-derived dendritic cells. Finally, in vivo data suggested good tissue integration and a minimal host inflammatory response when subcutaneously injected in rats. Collectively, these minimally invasive, browning-free, and strongly bioadhesive mussel-inspired cryogels show great promise for various biomedical applications, potentially in wound healing, tissue engineering, and regenerative medicine.

Biomimetic adhesives with a stiff fibre-reinforced base layer generate strong attachment, even without bioinspired micropatterning of the contact surface. However, current fibre-reinforced adhesive designs are still less versatile with respect to substrate variability than their biological counterparts. In this study, we enhance the comformability of a fibre-reinforced adhesive on curved substrates by adding bioinspired soft backings. We designed and fabricated soft backing variations (polyurethane foams and silicone hydroskeletons) with varying compressive stiffnesses that mimic the soft viscoelastic structures in the adhesive appendages of tree frogs, geckos and other animals. The backings were mounted on a smooth silicone layer enforced with a polyester mesh, and we experimentally investigated the contact area and friction performance of these adhesives on a curved substrate. The results show that the contact area and friction created by a fibre-reinforced adhesive with a soft backing in contact with a non-flat substrate scale inversely with backing stiffness. The integration of stiff fibre-reinforcement with a compressible backing represents an important step in bringing bioinspired adhesives out of the laboratory and into the real world, for example in soft robotic grippers. Moreover, our findings stimulate further research into the role of soft tissues in biological adhesive systems.

The study aims to investigate the adhesion of a hydrogel made of cross-linked low-methyl esterified pectin to rat intestinal serosa ex vivo. The adhesivity of the FeP hydrogel, which was cross-linked by Fe3+ cations, exceeded that of hydrogels cross-linked by Ca2+, Zn2+, and Al3+ cations. The concentration of the cross-linking cation failed to influence the adhesion of the pectin hydrogel to the serosa. The mechanical properties and surface microrelief of the pectin hydrogel were influenced by the type and concentration of the cross-linking cations. Fe3+ cations form a harder and more elastic gel than Ca2+ cations. Scanning electron microscopy analysis revealed the characteristic surface pattern of FeP hydrogel and its denser internal structure compared to Ca2+ cross-linked hydrogel. The effect of the salt composition of the adhesion medium was shown since the FeP hydrogel's adhesion to the serosa was lower in physiological solutions than in water, and adhesion in Hanks' solution was higher than in phosphate buffered saline. Serum proteins and peritoneal leukocytes did not interfere with the serosal adhesion of the FeP hydrogel. Pre-incubation in Hanks' solution for 24 h significantly reduced the adhesion of the FeP hydrogel to the serosa, regardless of the pH of the incubation. Thus, serosal adhesion combined with excellent stability and mechanical properties in physiological environments appeared to be advantages of the FeP hydrogel, demonstrating it to be a promising bioadhesive for tissue engineering. [ABSTRACT FROM AUTHOR]

Due to the low solubility and poor bioavailability of Ticagrelor (TIC), the current study developed a structured bioadhesive core-shell drug delivery system to address it. Ticagreior solid dispersion (T-SD) was fabricated using the uniaxial electrostatic spray method. Ticagrelor bio adhesive solid dispersion (T-BSD) was also prepared using the coaxial electrostatic spray technique. The adhesion of T-BSD to each intestinal segment was determined using biological adhesion test. The compartment model was used to study the plasma concentration-time curve and related pharmacokinetic parameters. The results of bioadhesion tests showed a positive adhesion effect of T-BSD in each intestinal segment. The maximum plasma concentration (Cmax) of T-BSD was increased to 777.08ng/mL compared with the free drug (367ng/mL). Similarly, t1/2, MRT and Tmax of T-BSD (12.1h, 9.4h, 4h) were higher than the free drug (11.2h, 8.6h, 1h), respectively. The relative bioavailability of T-BSD was further increased to 430% compared with the free drug. The findings collectively revealed that the coaxial-electrospray technique could be a promising way to improve the bioavailability of TIC. [ABSTRACT FROM AUTHOR]

Background: Poly(acrylic acid) (PAA) is a water-soluble synthetic polymer with tissue-adhesive properties. When PAA is mixed with polyvinylpyrrolidone (PVP) in water, it forms a water-insoluble precipitate that neither swells nor adheres to tissues. Methods and Results: We developed a novel solid/solution interface complexation method to obtain a water-swellable PAA/PVP complex. First, PAA solution was dried up in a vessel to form a film. The PAA film was then immersed in an aqueous PVP solution to obtain a highly swollen PAA/PVP hydrogel. Heat drying of the hydrogel yielded a transparent film, while freeze-drying the hydrogel provided a soft sponge. Both the PAA/PVP film and sponge could be re-swelled by water to obtain a bioadhesive gel. A relatively larger specific surface area of the sponge than that of the film led to a more rapid swelling and water absorption behavior and quick adhesion to tissues. The addition of hyaluronic acid (HA) improved the mechanical characteristics of the sponges. PAA/PVP/HA sponges had low cytotoxicity, and they exhibited high hemostatic efficiency in clinical studies after dialysis treatment or tooth extraction, even in patients on antithrombotic drugs. Conclusions: Such bioadhesive materials consisting of low-toxicity polymers have a high potential for use in medical hemostatic devices. [ABSTRACT FROM AUTHOR]

Unworn masks and masks provided to us after having been worn conformable to law (mandatory wearing of masks) served as test objects. In order to identify the distribution of living microorganisms on the surface of a mask dependent on exposure time and distance from the human face we conducted a staining study using the bengal rose method. The regular deposition of living microorganisms on artificial mask surfaces was more intense in the areas close to the mouth and nose. A time dependent accumulation was larger on the inside in comparison to the outside of the mask, even if the mask was not worn but only left in the room. The most interesting finding was the ability of microorganisms to penetrate all layers of the mask. We therefore conclude that masks are a suitable substrate for the cultivation of germs, even when not worn. Colonisation increases with human use and with time.

Secretome is involved in almost all physiological, developmental, and pathological processes, but to date there is still a lack of highly-efficient research strategy to comprehensively study the secretome of invertebrates. Adhesive secretion is a ubiquitous and essential physiological process in aquatic invertebrates with complicated protein components and unresolved adhesion mechanisms, making it a good subject for secretome profiling studies. Here we proposed a computational pipeline for systematic profiling of byssal secretome based on spatiotemporal transcriptomes of scallop. A total of 186 byssus-related proteins (BRPs) were identified, which represented the first characterized secretome of scallop byssal adhesion. Scallop byssal secretome covered almost all of the known structural elements and functional domains of aquatic adhesives, which suggested this secretome-profiling strategy had both high efficiency and accuracy. We revealed the main components of scallop byssus (including EGF-like domain containing proteins, the Tyr-rich proteins and 4C-repeats containing proteins) and the related modification enzymes primarily contributing to the rapid byssus assembly and adhesion. Spatiotemporal expression and co-expression network analyses of BRPs suggested a simultaneous secretion pattern of scallop byssal proteins across the entire region of foot and revealed their diverse functions on byssus secretion. In contrast to the previously proposed “root-initiated secretion and extension-based assembly” model, our findings supported a novel “foot-wide simultaneous secretion and in situ assembly” model of scallop byssus secretion and adhesion. Systematic analysis of scallop byssal secretome provides important clues for understanding the aquatic adhesive secretion process, as well as a common framework for studying the secretome of non-model invertebrates.

Eutectogels (Egels) are an emerging class of soft ionic materials outperforming traditional temperature-intolerant hydrogels and costly ionogels. Due to their excellent elasticity, non-volatile nature, and adhesion properties, Egels are attracting a great deal of interest in the biomedical space. Herein, we report the first example of adhesive Egels loading drug nanocrystals (Egel-NCs) for controlled delivery to mucosal tissues. These soft materials were prepared using gelatin, glycerine, a deep eutectic solvent (DES) based on choline hydrochloride and glycerol, and nanocrystallised curcumin, a model drug with potent antimicrobial and anti-inflammatory activities. We first explored the impact of the biopolymer concentration on the viscoelastic and mechanical properties of the networks. Thanks to the dynamic interactions between gelatin and the DES, the Egel showed excellent stretchability and elasticity (up to ≈160%), reversible gel-sol phase transition at mild temperature (≈50 ​°C), 3D-printing ability, and good adhesion to mucin protein (stickiness ≈40 ​kPa). In vitro release profiles demonstrated the ability of the NCs-based Egel to deliver curcumin for up to four weeks and deposit significantly higher drug amounts in excised porcine mucosa compared to the control cohort. All in all, this study opens new prospects in designing soft adhesive materials for long-acting drug delivery and paves the way to explore novel eutectic systems with multiple therapeutic applications.

Although some methods for measuring bioadhesion/mucoadhesion have been proposed, a standardized method is not yet available. This is expected to hinder systematic comparisons of results across studies. This study aimed to design a single/systematic in vitro method for measuring bioadhesion/mucoadhesion that is applicable to various pharmaceutical dosage forms. To this end, we measured the peak force and work of adhesion of minitablets, pellets, and a bioadhesive emulsion using a texture analyzer. Porcine tissue was used to simulate human stomach/skin conditions. The results of these formulations were then compared to those for formulations without the bioadhesive product. We conducted a case study to assess the stability of a bioadhesive emulsion. The results for the two parameters assessed were contact time = 60 s and contact force = 0.5 N at a detachment speed of 0.1 mm/s. Significant differences were observed between the bioadhesive and control formulations, thus demonstrating the adhesive capacity of the bioadhesive formulations. In this way, a systematic method for assessing the bioadhesive capacity of pharmaceutical dosage forms was developed. The method proposed here may enable comparisons of results across studies, i.e., results obtained using the same and different pharmaceutical formulations (in terms of their bioadhesion/mucoadhesion capacity). This method may also facilitate the selection of potentially suitable formulations and adhesive products (in terms of bioadhesive properties). [ABSTRACT FROM AUTHOR]

This study was aimed to prepare, optimize and characterize cost-effective and mucoadhesive dental minocycline microspheres for the treatment of periodontitis. There is a need and scope for a costeffective novel formulation of minocycline for periodontitis that can be delivered to the base of the pockets and is biodegradable, bioadhesive, and non-toxic. The Central composite design (CCD) was utilized to study the effects of process variables (5 levels) on the responses including size (R1), drug-entrapment (R2), mucoadhesion (R3), and percent in-vitro drug release (R4). Chitosan-minocycline microspheres were prepared by W/O emulsion technique using glutaraldehyde and sodium tripolyphosphate as different cross-linking agents. Results indicated that the concentration of polymer, drug, cross-linking agent, and cross-linking method significantly affected drug incorporation efficiencies and microsphere characteristics. The minocycline release from the microspheres provided a retarded release up to 8 h and all concentrations were observed to be more than the minimum inhibitory concentration (MIC) required for inhibiting the growth of Staphylococcus aureus. The study concluded that the microspherical system provides advantages over systemic drug administration, including reduction of systemic side effects and dramatic increase in sustained drug concentrations in the gingival cervicular fluid. Local delivery by means of microspheres has several advantages over systemic drug intake including lesser systemic side effects, reduction of dose, mucoadhesiveness, and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Before entering metamorphosis, the larvae of Drosophila flies expel a transparent glue from their mouth, which solidifies in contact with air within seconds and fixes the animal to a substrate (wood, leaves, fruits, stones, etc.) for several days until the adult emerges. This glue displays interesting adhesive properties, as it can adhere to various substrates with strengths similar to strongly adhesive commercial tapes. We review here the production, aspect, composition and role of this glue in the model organism Drosophila melanogaster and in other Drosophila species. The glue is made of several proteins, which have diversified rapidly during evolution. With the large diversity of substrates and environmental conditions where fly species undergo metamorphosis, Drosophila glue provides a large source of inspiration for the development of biomimetic adhesive materials. We propose several potential avenues of research for the future development of Drosophila-inspired adhesive materials. The glue produced by Drosophila larvae to attach themselves to a substrate for several days and resist predation until the end of metamorphosis represents an attractive model to develop new adhesives for dry environments. The adhesive properties of this interesting material have been investigated recently, and it was found that it binds as well as strongly adhesive commercial tapes to various types of substrates. This glue hardens rapidly after excretion and is made of several proteins. In D. melanogaster, eight glue proteins have been identified: four are long glycosylated mucoproteins containing repeats rich in prolines, serines and threonines, and four others are shorter proteins rich in cysteines. This protein mix is produced by the salivary glands through a complex packaging process that is starting to be elucidated. Drosophila species have adapted to stick to various substrates in diverse environmental conditions and glue genes appear to evolve rapidly in terms of gene number, number of repeats and sequence of the repeat motifs. Interestingly, besides its adhesive properties, the glue may also have antimicrobial activities. We discuss future perspectives and avenues of research for the development of new bioadhesives mimicking Drosophila fly glue. [ABSTRACT FROM AUTHOR]

Poly(acrylic acid) (PAA) is a water-soluble synthetic polymer that exhibits bioadhesive properties and has been applied in various novel medical devices, such as drug-delivery carriers and hemostatic agents. PAA forms a water-insoluble complex when mixed with polyvinylpyrrolidone (PVP). If PAA and PVP are mixed in water, they form an aggregated precipitate, which neither swells nor adheres to tissues. The formation of the hydrophobic complex was caused by hydrophobic interactions between the main chains of both polymers aligned the same as a zipper. To hinder the zipper-like alignment of the polymer main chains, hyaluronic acid (HA), a macromolecular viscous polysaccharide, was added to the PVP solution prior to complex formation. When the initial concentration of PAA was lower than 0.05%, HA effectively prevented the aggregation of PAA/PVP complexes and resulted in a slightly clouded suspension. Freeze-drying of the mixture yielded a soft white sponge, which could immediately swell in water to form a highly bioadhesive hydrogel. The PAA/PVP complex prepared with HA exhibited high hemostatic efficiency in clinical studies, even in patients on antithrombotic drugs. [ABSTRACT FROM AUTHOR]

The research on the impact of plastic pollution on biodiversity has primarily focused on aquatic ecosystems, especially marine ones. Therefore, it is vital to assess how plastic pollution affects other environments and organisms, including terrestrial invertebrates. These organisms are widely recognized for their susceptibility to environmental changes and pollution. The objectives of this study were i) to investigate the potential influence (positive or negative) of macroplastic debris (MaP) on invertebrates inhabiting riverine sandy environments, ii) the potential occurrence of the microplastic (MP) adherence phenomenon on the invertebrate's body by entanglement on the body's setae or electrostatic effect (i.e., bioadhesion), and iii) the effects of removal of debris on the colonized diversity. By performing a mesocosm experiment, emulating a "small-scale dump" (also called micro-waste sites), we found that terrestrial invertebrates show a preference for colonizing areas rich in MaP, resulting in higher species richness in these areas (39 taxa in areas containing plastic debris vs. 21 taxa in areas free of plastics). This preference is likely due to the provision of shade, protection, and distinct micro-habitats offered by MaP. Regarding MP, we observed a significant number of invertebrates with MPs attached to their bodies (4.3 ± 0.8 MPs attached per individual), mainly wolf spiders (Lycosidae) and ground beetles (Carabidae), suggesting potential negative ecological implications that are discussed herein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hazelnut shells, the main waste deriving from hazelnut processing, represent an interesting source of active molecules useful in pharmaceutics, although they have not yet been examined in depth. A hydrosoluble extract (hazelnut shell extract, HSE) was prepared by the maceration method using a hydroalcoholic solution and used as the active ingredient of patches (prepared by casting method) consisting of composites of highly deacetylated chitosan and green clay. In vitro studies showed that the formulation containing HSE is able to stimulate keratinocyte growth, which is useful for healing purposes, and to inhibit the growth of S. aureus (Log CFU/mL 0.95 vs. 8.85 of the control after 48 h); this bacterium is often responsible for wound infections and is difficult to treat by conventional antibiotics due to its antibiotic resistance. The produced patches showed suitable tensile properties that are necessary to withstand mechanical stress during both the removal from the packaging and application. The obtained results suggest that the developed patch could be a suitable product to treat wounds.

Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging. We have synthesized HA-Dopamine conjugates (HA-Dop) with several degrees of substitution (DS) and used two crosslinking methods: initiator-free crosslinking by basic pH shift or commonly used crosslinking by a strong oxidizer, sodium periodate. The rheological properties, bioadhesion to vascular tissue, cytocompatibility with fibroblasts have been compared for both methods. Our results suggest that initiator-free crosslinking provides HA-Dop gels with more adequate properties with regards to vascular application than crosslinking by strong oxidizer. We have also established the cytocompatibility of the initiator-free crosslinked HA-Dop gels and the cytotoxicity of dopamine-sodium periodate combinations. Furthermore, we have incorporated a drug with anti-restenotic effect in perivascular application, atorvastatin, into the gel, which showed adequate release profile for intimal hyperplasia prevention. The oxidizer-free formulation with improved bioadhesion holds promise as an efficient and safe drug delivery system for vascular applications. [ABSTRACT FROM AUTHOR]

Intravesical instillation allows for direct exposure of the urothelium to a drug. However, the therapeutic efficacy is often limited by the rapid elimination of the drug from the bladder. In this investigation, it is hypothesized that the morphology of nanoparticulate drug delivery systems could significantly impact bioadhesion and bioelimination from the bladder. Bioadhesion kinetics evaluated ex vivo on rat bladder mucosa demonstrates that particles with a flattened morphology, denoted as nanoplatelets, are rapidly attached to the mucosa at a lower concentration than nanospheres. The two particles have comparable surface potentials and equivalent volumes and are composed of hyaluronan, a nonsulfated polysaccharide that plays a significant role in restoring the bladder glycosaminoglycan layer. The bioaccumulation and bioelimination studied in vivo reveal that the nanoplatelets are eliminated from the rat bladders less rapidly than nanospheres. This investigation suggests that the bioadhesion of HA could be improved by optimizing particle morphology, opening new opportunities for the treatment of local urothelial diseases, such as interstitial cystitis/painful bladder syndrome, by restoring the loss of the glycosaminoglycan layer.

The aim of this study was to develop a suitable clotrimazole (CLT)-loaded mucoadhesive vaginal gel (CLT-MVG) for topical applications in vaginal candidiasis. Ten CLT-MVG formulations were prepared, consisting of mixtures of acid polyacrylic (Carbopol 940) and polyethene oxides, Sentry Polyox WSRN 1105 or 750, according to an experimental D-optimal design, and CLT was suspended at a ratio of 1%. The prepared CLT-MVG formulations were studied in vitro, and the formulation containing Carbopol 940 0.89% combined with PEO 1105 1.39% was identified with the optimal rheological and in vitro bioadhesion properties, ensuring the prolonged release of CLT, with a similarity factor greater than 50, indicating dissolution profile similarity for three batches of the optimized formulation. This optimized formulation showed a pH in the tolerance range, and an adequate ex vivo mucoadhesion time, while the FT-IR studies revealed no interactions between the excipients and CLT. The microscopic analysis identified a mean particle size of suspended CLT of 5.24 ± 0.57 μm. The in vitro antifungal activity of the optimized formulation was tested on twenty strains of Candida albicans and proved to be better compared to a marketed clotrimazole preparation, showing a greater inhibition effect (p < 0.05). The optimized formulation could be a good candidate for the local treatment of vaginal mycosis.

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities and for this reason useful to be used in a wound care product. Bioadhesive polymeric patches have been realized by combining acacia gum (AG) and polyvinylpyrrolidone (PVP). Prototypes were prepared by considering different AG/PVP ratios and the most suitable in terms of mechanical and bioadhesion properties resulted in the 9.5/1.0 ratio. This patch was loaded with GSE combined with cyclic dextrin (CD) to obtain the molecular dispersion of the active ingredient in the dried formulation. The loaded patch resulted mechanically resistant and able to release GSE by a sustained mechanism reaching concentrations able to stimulate keratinocytes' growth, to exert both antibacterial and antioxidant activities. [ABSTRACT FROM AUTHOR]

Oral dissolving films are advanced oral dosage forms implied for the attachment onto the buccal mucosa and have both local and systemic effects. These dosage forms may be favored over other oral drug delivery systems in terms of flexibility and comfort. These films utilize the property of bioadhesion of certain polymers, which on hydration target a particular region of the body for extended period of time thereby bypassing first pass metabolism and promoting increased bioavailability. These films are self-administrable, pharmacoeconomic and have good patient compliance. Various techniques may be used for the formulation of oral dissolving films, among which solvent casting method is the most preferable. Usually hydrophilic polymers along with other excipients are used to formulate buccal films, which disintegrate quickly releasing the incorporated APIs within seconds. Oral dissolving films offer numerous benefits as far as accessibility, administration and withdrawal, retentivity, low enzymatic movement, economy and high patient compliance is concerned, thus having the potential for market and business exploitation. This preset review emphasizes on mechanism of action, merits, composition, formulation, evaluation, marketed formulations of oral dissolving films. Additionally, covering the aspects related to novel fast dissolving techniques. [ABSTRACT FROM AUTHOR]

Unworn masks and masks provided to us after having been worn conformable to law (mandatory wearing of masks) served as test objects. In order to identify the distribution of living microorganisms on the surface of a mask dependent on exposure time and distance from the human face we conducted a staining study using the bengal rose method. The regular deposition of living microorganisms on artificial mask surfaces was more intense in the areas close to the mouth and nose. A time dependent accumulation was larger on the inside in comparison to the outside of the mask, even if the mask was not worn but only left in the room. The most interesting finding was the ability of microorganisms to penetrate all layers of the mask. We therefore conclude that masks are a suitable substrate for the cultivation of germs, even when not worn. Colonisation increases with human use and with time. [ABSTRACT FROM AUTHOR]

Raloxifene (RLX) is a second-generation selective estrogen receptor modulator used to treat osteoporosis in postmenopausal women. RLX fails to be developed into injectable dosage forms due to poor solubility. Although oral formulations are clinically available, the lower bioavailability (

Roberta Salaroli,1 Domenico Ventrella,1 Chiara Bernardini,1 Alberto Elmi,1 Augusta Zannoni,1,2 Maria Laura Bacci,1,2 Monica Forni,1,2 Fiorella Calanni,3 Antonella Ferrieri,4 Fabio Baldi5 1Department of Veterinary Medical Science, University of Bologna, Ozzano Emilia, Bologna, Italy; 2Health Sciences and Technologies Interdepartmental Center for Industrial Research, University of Bologna, Bologna, Italy; 3Pre-Clinical Research Department, Alfasigma, Bologna, Italy; 4Division of Clinical Research, Department of Research and Development, Alfasigma, Bologna, Italy; 5Center for the Study of Diseases of the Esophagus, University of Bologna and Gruppo Villa Maria Care & Research, Ravenna, ItalyCorrespondence: Monica ForniDepartment of Veterinary Medical Science, University of Bologna, Via Tolara, 50, Ozzano Emilia 40064, Bologna, ItalyTel +39 051 20 9 7913Email monica.forni@unibo.itPurpose: AL2106 is a new medical device based on a mixture of chondroitin sulphate in a xyloglucan and glycerol solution made to maximize its bioadhesive capability to the esophageal mucosa. The aim of the present study was twofold to evaluate the AL2106 protective effect on the esophageal mucosa when exposed to an acidic solution mimicking gastric reflux and to assess the resilience of this effect to saline washing.Materials and Methods: A porcine ex vivo model was used and the effects of the new medical device were compared to a sodium alginate suspension (SAS) already present on the market which was assumed as reference. Mucosal damage was induced in 19 porcine esophagi by perfusion with an acidic solution added with pepsin, and Evans blue dye (EBD) tissue uptake was used as an indicator of mucosal permeability. The EBD penetration, expressed as EBD μg/g of dry tissue, was assessed in specimens of untreated damaged mucosa and in specimens treated with AL2106 or SAS. The same evaluation was carried out after washing with normal saline.Results: Both topical agents tested significantly reduced the EBD uptake by more than 60% (AL2106 8.4± 4.5, SAS 3.6± 2.7 vs control 23.2± 13.1, p< 0.01). The saline washing did not cause any significant reduction in the protective effect of AL2106 (8.6± 5.9), while it significantly reduced that of SAS (5.9± 4.3, p< 0.05).Conclusion: The new AL2106 medical device showed a good barrier effect against a reflux-like damaging solution and preserved this effect after the mucosal washing test, thus suggesting its possible relevance for the treatment of gastroesophageal reflux disease.Keywords: bioadhesion, Evans blue dye, EBD, animal model, esophagus, gastroesophageal reflux disease, GERD

Atherosclerotic plaques and thrombosis are chronic inflammatory complications and the main manifestations of cardiovascular diseases (CVD), the leading cause of death globally. Achieving non/minimal-invasive therapeutic means for these implications in the coronary network is vital and has become an interdisciplinary concern. Accordingly, smart drug delivery systems, specifically based on micro- and nanoparticles, as a promising method to offer non/minimal-invasive therapeutic mechanisms are under active research. Notably, computational models enable us to study, design, and predict treatment strategies based on smart drug delivery systems with less time and cost compared with conventional procedures in interventional cardiology. Also, the optimisation and development of computational methods and models have created a broad and practical insight into patient-specific drug design and therapeutic interventions. This review discusses the most recent works on the transport, dynamics, and delivery of particles as drug carriers to target thrombus, inflamed surfaces, and atherosclerotic plaques. Towards understanding and producing optimised particle-based cardiovascular drug delivery systems, this review conveys an original and multifaceted image on the modelling for drug carrier design.

Advances in nanotechnology have generated a broad range of nanoparticles (NPs) for numerous biomedical applications. Among the various properties of NPs are functionalities being related to thiol substructures. Numerous biological processes that are mediated by cysteine or cystine subunits of proteins representing the workhorses of the bodies can be transferred to NPs. This review focuses on the interface between thiol chemistry and NPs. Pros and cons of different techniques for thiolation of NPs are discussed. Furthermore, the various functionalities gained by thiolation are highlighted. These include overall bio‐ and mucoadhesive, cellular uptake enhancing, and permeation enhancing properties. Drugs being either covalently attached to thiolated NPs via disulfide bonds or being entrapped in thiolated polymeric NPs that are stabilized via inter‐ and intrachain crosslinking can be released at the diseased tissue or in target cells under reducing conditions. Moreover, drugs, targeting ligands, biological analytes, and enzymes bearing thiol substructures can be immobilized on noble metal NPs and quantum dots for therapeutic, theranostic, diagnostic, biosensing, and analytical reasons. Within this review a concise summary and analysis of the current knowledge, future directions, and potential clinical use of thiolated NPs are provided. [ABSTRACT FROM AUTHOR]

Raloxifene (RLX) is a second-generation selective estrogen receptor modulator used to treat osteoporosis in postmenopausal women. RLX fails to be developed into injectable dosage forms due to poor solubility. Although oral formulations are clinically available, the lower bioavailability (<2%) embarrasses the pharmaceutists. This work reported a bioadhesive nanosystem intended for oral delivery of RLX to enhance its oral bioavailability and address the formulation challenge. The bioadhesive nanosystem refers to polymer–lipid hybrid nanoparticles made up of Carbopol 940, glyceryl distearate, and TGPS. RLX was solidly encapsulated into bioadhesive nanoparticles (bNPs) through a nanoprecipitation technique along with synchronous desalting of RLX·HCl. The resultant RLX-loaded bNPs (RLX-bNPs) were characterized by particle size, ζ potential, morphology, and entrapment efficiency. The in vitro release and in vivo oral bioavailability of RLX-bNPs in rats were comparatively investigated with RLX-loaded common lipid nanoparticles (RLX-cNPs). The preferred formulation possesses a particle size of 150 nm around with a polydispersity index (PDI) of 0.282. RLX-bNPs exhibited slower drug release than RLX-cNPs owing to the presence of an adhesive layer. After oral administration, RLX-bNPs resulted in significant enhancement in the bioavailability of RLX, up to 556.9% relative to RLX suspensions, while it was merely 244.7% for RLX-cNPs. Cellular testing and ex vivo transport imaging demonstrated that bNPs were endowed with excellent intestinal epithelial affinity and absorbability. Our study affords an alternative option for designing a suitable oral delivery system specific to amphiphobic drugs like RLX·HCl. [ABSTRACT FROM AUTHOR]

The aim of this research was to test the potential of applying a flow cytometric procedure to evaluate the impact of concrete compounds' release to the freshwater microbiome. Cells from the collected samples were stained with a fluorogenic redox indicator dye that measures the redox potential of microbial cells. This novel approach was combined with the assessment of microorganisms' penetration into the internal structures of concrete using the Rose Bengal sodium salt staining. Rose Bengal staining revealed an intense fouling of the upper and side walls of the concrete cubes and also indicated the penetration of microorganisms inside the concrete as observed for the cubes' cross-sections. Flow cytometric cellular redox potential measurement revealed high percentages of active cells within the concrete's porous structures and in non-exposed water (32.7% and 30.2% of active cells) versus samples from exposed water and concrete's outer surfaces (6.8%, 6.1%, and 3.3% of active cells). The results demonstrated a detrimental impact of hydro-technical concrete on the vitality of microbial cells within the freshwater environment. Tested protocol by analyzing the physiology of microbial cells improved the functional description of complex communities to evaluate the fate of contaminants present in the concrete-based hydro-technical infrastructure. [ABSTRACT FROM AUTHOR]

Abstract Background The mechanism by which sea anemones attach to surfaces underwater remains elusive, which is surprising given their ubiquitous distribution in the world’s oceans and tractability for experimental biology. Their adhesion is mechanically interesting, bridging the interface between very hard and soft materials. The Cnidaria are thought to have evolved adhesion to surfaces at least 505 Ma ago implying that, among the Metazoa, only Porifera developed this capability earlier. The purpose of this study was primarily to address an existing hypothesis, that spirocysts (a sticky class of cnidocyst) facilitate adhesion to surfaces, as observed during prey capture. Results We demonstrated conclusively that spirocysts were not involved in the pedal disc adhesion of Exaiptasia pallida. Second, we applied a variety of imaging methods to develop an understanding of the true adhesion mechanism. Morphological studies using scanning electron microscopy identified a meshwork of adhesive material, unique to the pedal disc. Serial block-face SEM highlighted four classes of cells that could secrete the adhesive from the pedal disc ectoderm. A variety of histochemical techniques identified proteins, glycans and quinones in the cell contents and secreted adhesive, with variation in contents of specific cell-types in different areas of the body. Conclusions Spirocysts are not used by Exaiptasia pallida for adhesion to surfaces. Instead, a structurally and compositionally complex secreted glue was observed, firmly attaching the animals underwater. The results of this study provide a basis for further investigations of adhesion in Cnidaria, and establish E. pallida as a new model organism for bioadhesion research.

Introduction. There are a number of drugs, the absorption zone of which is the upper region of the gastrointestinal tract (GIT) – the stomach and duodenum. To increase bioavailability, gastroretentive (intragastric) systems for the controlled drug delivery are being developed. To date, there are various approaches to ensure intragastric drug delivery. One of the most promising approaches is the use of excipients with bioadhesive properties, both individually and in combination with other types of gastroretentive systems.Aim. Development and research of new carriers for gastroretentive bioadhesive drug delivery systems based on interpolyelectrolyte complexes (IPEC) with the participation of chemically complementary poly(meth)acrylates of the Eudragit®.Materials and methods. The study of swelling ability was carried out in a medium of 0.1 M hydrochloric acid solution (pH 1.2) at a temperature of 37 ± 0.5 °C for 6 hours. The study of the release of metronidazole (MZ) from matrices based on the corresponding IPEC was performed on a DFZ II instrument (ERWEKA, Germany) according to the Flow Trough Cell method in 0.1 M HCl medium, pH 1.2, flow rate 4 ml/min in a closed cycle within 6 hours. The amount of released MZ was estimated by UV spectrophotometry on a Lambda 25 instrument (PerkinElmer, USA) at a wavelength of 274 nm. IPEC adhesion was studied using a TA.XTplus texture analyzer (Stable Micro Systems, UK).Results and discussion. Matrices based on IPEC 1 were disintegrated after being in a medium with a pH of 1.2 for 4 hours, matrices based on IPEC 4 were dissolved in an acidic medium for 3 hours. At the same time, matrices based on IPEC 2 and IPEC 3 retain their shape throughout the experiment and are characterized by rather high values of the degree of swelling. IPEC samples are characterized by higher adhesion performance compared to individual copolymers. The release of metronidazole from matrices based on IPEC 1 occurs in accordance with Fick's law of diffusion; from the matrix based on IPEC 4, MZ is released according to the anomalous transport mechanism.Conclusion. IPEC 3 is promising for use as carrier for gastroretentive bioadhesive systems of controlled delivery of metronidazole.

Abstract Advances in nanotechnology have generated a broad range of nanoparticles (NPs) for numerous biomedical applications. Among the various properties of NPs are functionalities being related to thiol substructures. Numerous biological processes that are mediated by cysteine or cystine subunits of proteins representing the workhorses of the bodies can be transferred to NPs. This review focuses on the interface between thiol chemistry and NPs. Pros and cons of different techniques for thiolation of NPs are discussed. Furthermore, the various functionalities gained by thiolation are highlighted. These include overall bio‐ and mucoadhesive, cellular uptake enhancing, and permeation enhancing properties. Drugs being either covalently attached to thiolated NPs via disulfide bonds or being entrapped in thiolated polymeric NPs that are stabilized via inter‐ and intrachain crosslinking can be released at the diseased tissue or in target cells under reducing conditions. Moreover, drugs, targeting ligands, biological analytes, and enzymes bearing thiol substructures can be immobilized on noble metal NPs and quantum dots for therapeutic, theranostic, diagnostic, biosensing, and analytical reasons. Within this review a concise summary and analysis of the current knowledge, future directions, and potential clinical use of thiolated NPs are provided.