Ginseng encapsulated Poly(Lactic-co-Glycolic Acid)/ Polyaniline microcapsules coated on stainless steel 316L using electrodeposition technique for drug-eluting stent application

Drug-eluting stent (DES) has successfully minimised the occurrence of restenosis and in-stent neointimal formation. However, its drawback of polymer hypersensitivity is often led to late-stent thrombosis. Besides, incomplete coating and bridging on stent surfaces as well as rapid release of anti-proliferative drugs to the site of implantation have contributed to late endotheliasation. The incorporation of ginseng within biodegradable polymer coating will address these issues due to its specific therapeutic values. Therefore, 30 mg ginseng was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microcapsules to be electrodeposited as a coating on stainless steel 316L (SS316L). A proficient technique of electrodeposition was performed at different currents (1 - 3 mA) and deposition times (20 - 60 seconds) while different polyaniline (PANI) compositions (0.5 - 2.0 mg) were also adopted in the electrodeposition process to drive the formation of microcapsules coating. Based on different currents and deposition times, it was found that electrodeposition with addition of PANI conducted at 2 mA current and 40 seconds deposition time has formed low wettability and uniform microcapsules coating through the analyses of ATR-FTIR, SEM and contact angle. Reduction in current or deposition time caused less attachment of microcapsules coating with high wettability records. Increasing current or prolonging deposition time has led to debris formation and melted microcapsules with non-uniform wettability measurements. The colour of electrolytes was also changed from milky white to dark yellow when the current and the deposition time increased. Based on different composition of PANI, the utilisation of 1.5 mg PANI has assisted the formation of stable, uniform and rounded microcapsules coating with appropriate wettability and surface roughness through the ATR-FTIR, XPS, SEM, AFM and contact angle analyses. Low PANI content (0.5 mg) was not enough to drive the formation of microcapsules coating while higher content of PANI (2.0 mg) caused the deposition of melted microcapsules. A month coating stability analysis showed that the coating stability was improved at the utilisation of 1.5 mg PANI with moderate PLGA degradation and less appearance of melted microcapsules. The similar coating also has promoted greater endothelial cell proliferation and attachment compared to other coating variation through MTT assay and VP-SEM analyses. The capabilities of ginseng encapsulated PLGA/PANI microcapsules coating in delivering its therapeutic values would be beneficial in addressing the complication of current DES

Electrodeposition of ginseng/polyaniline encapsulated poly(lactic-co-glycolic acid) microcapsule coating on stainless steel 316L at different deposition parameters

Electrodeposition is commonly used to deposit ceramic or metal coating on metallic implants. Its utilization in depositing polymer microcapsule coating is currently being explored. However, there is no encapsulation of drug within polymer microcapsules that will enhance its chemical and biological properties. Therefore, in this study, ginseng which is known for its multiple therapeutic effects was encapsulated inside biodegradable poly(lactic-co-glycolic acid) (PLGA) microcapsules to be coated on pre-treated medical grade stainless steel 316L (SS316L) using an electrodeposition technique. Polyaniline (PANI) was incorporated within the microcapsules to drive the formation of microcapsule coating. The electrodeposition was performed at different current densities (1–3mA) and different deposition times (20–60s). The chemical composition, morphology and wettability of the microcapsule coatings were characterized through attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM) and contact angle analyses. The changes of electrolyte colors, before and after the electrodeposition were also observed. The addition of PANI has formed low wettability and uniform microcapsule coatings at 2mA current density and 40s deposition time. Reduction in the current density or deposition time caused less attachment of microcapsule coatings with high wettability records. While prolonging either one parameter has led to debris formation and melted microcapsules with non-uniform wettability measurements. The color of electrolytes was also changed from milky white to dark yellow when the current density and deposition time increased. The application of tolerable current density and deposition time is crucial to obtain a uniform microcapsule coating, projecting a controlled release of encapsulated drug

Acetyl Rb1 Ginsenoside from North American Ginseng: Extraction and Application

North American ginseng is a unique medicinal plant which is believed to show several biological activities including: anti-stress, anti-angiogenic, immunosuppressive, and anti-oxidant activity. Components previously isolated from North American ginseng include ginsenosides, polysaccharides, peptides, polyacetylenic alcohols, and fatty acids. The biological and pharmacological effects of ginseng are mainly related to the ginsenoside components, making their extraction and characterization of interest in order to identify them, and study their biological activities. This thesis focused on the extraction of ginsenosides from North American ginseng by an ultrasonication method with methanol and DMSO as solvents and their aqueous mixtures. Quantitative analysis of individual ginsenosides from the extracts was measured by HPLC, which demonstrated that ultrasonication significantly enhanced the extraction efficiency, with the best efficiency found using 80% solvent (methanol, and DMSO) and 20% water. Immunosuppressive activity of these ginseng extracts was tested in LPS-induced macrophage cells showing that the 80% DMSO and 80% methanol extracts gave significant potency toward immunosuppressive activity in a dose-dependent manner. Moreover, significant quantities of 6”-O-acetylginsenoside Rb1 were obtained using DMSO as the extraction solvent during ultrasonication, and identified using MS, FTIR, and 1D (1H and 13C) and 2D (gCOSY, gHSQC, and gHMBC) NMR. Also, subsequent bioassay experiments confirmed that acetyl ginsenoside Rb1 demonstrated additional immunosuppressive activity towards inhibiting the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in LPS-induced macrophage cells in a dose-dependent manner using murine macrophages. In addition, acetyl ginsenoside Rb1 gave significant anti-angiogenic activity and exhibited enhanced potency towards inhibiting tube-like structure formation of endothelial cells. Supercritical fluid chromatography (SFC) using supercritical carbon dioxide which is considered as a “green” separation method and believed as a promising technique for separation, isolation, and identification of herbal and medicinal plants, was used to separate and isolate ginseng extracts obtained by supercritical CO2 extraction (SFE). The effect of temperature and pressure on the separation of ginsenosides was studied with methanol being added to the CO2 mobile phase. Acidic, basic, and ionic additives were introduced to the mobile phase, respectively, to study their effect on the separation of ginsenosides. The best separation condition was obtained by adding 0.05% v/v trifluoroacetic acid in methanol. A high-concentration component in the extracts from the supercritical fluid extraction of North American ginseng was isolated by SFC and identified as sucrose using NMR, HPLC, and ESI-MS. Because of it\u27s unique biological activities, development of a suitable delivery system for acetyl ginsenoside Rb1 (ac-Rb1) was investigated for the first time in this research. PLGA microspheres were used to encapsulate ac-Rb1,examining both a double emulsion and a microfluidic technique. The size and morphology of the ac-Rb1 loaded PLGA microspheres were characterized by SEM and ZEISS light microscopy, showing unimodal 50-65 µm size diameters, respectively using the microfluidic technique. Also, another delivery system of PLGA in gelatin hydrogel was prepared in order to achieve a localized delivery method, overcoming drawbacks such as PLGA removal by macrophages and a high initial burst effect from gelatin hydrogel that can damage tissues around the injection site. The ac-Rb1 loaded microspheres were incorporated into the gelatin hydrogels to form a new delivery system examining gluteradlehyde crosslinking concentrations from 10-100µl. FTIR, DSC and TGA confirmed the formation and chemical stability of the gelatin encapsulated composites. Release profiles were studied and quantified by UV-Vis spectrophotometry with the results showing that the release of ac-Rb1 from the unimodal microspheres prepared by the microfluidic technique showed a lower initial burst effect than those from the double emulsion method. The burst effect was followed by a slow release profile which can be used for long term drug delivery applications to maintain the ginsenoside concentration for an extended time period. It should be mentioned that although the large burst effect could release a therapeutic agent relatively fast, it can also damage tissues around the treatment site. Hence, a combination delivery system was developed using cross-linked gelatin. The release of ac-Rb1 from the cross-linked gelatin encapsulated microspheres was effected by the pH of the releasing medium as well as the crosslinker concentration. Then, the in vitro cumulative release data of the core and core-composite systems was analyzed using empirical equations in Matlab. The results showed that the in vitro release kinetics data followed Fickian diffusion with the best fit observed using the Weibull model, for all investigated cases. Moreover, the released ac-Rb1 from delivery systems showed a significant immunosuppressive effect on LPS-induced macrophages indicating the novel delivery systems for ac-Rb1 have potential for next-generation biomedical agents in drug-release devices

Supercritical technologies as sustainable tool for the concentration and co-encapsulation of Lavandula luisieri natural bioactives

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, leída el 27-01-2021Tradicionalmente, las plantas han sido utilizadas para el tratamiento y prevención de enfermedades o conservación de alimentos. Su diversa aplicación deriva de la producción de metabolitos secundarios como defensa contra agentes externos dañinos, mostrando una variada actividad con interés en diferentes campos. De hecho, la inclusión de plantas como herramienta terapéutica en los sistemas de salud está recomendada por organismos internacionales como la OMS. Actualmente el 52% de los fármacos son o bien un compuesto natural o un derivado del mismo, con un interés comercial creciente debido ala preferencia que los consumidores muestran los productos de origen natural como parte de hábitos de vida saludables para la prevención de enfermedades crónicas..Traditionally, plants have been used for the treatment and prevention of diseases or food conservation. These diverse applications are a consequence of the production of secondary metabolites as defence against external damaging agents, presenting a varied activity with interest in many fields. In fact, the inclusion of plants as therapeutical tool in health systems is recommended by international organisations like the WHO. Nowadays, 52% of drugs are a natural compound or a derivate, and have a growing commercial interest because of the consumers’ preference for natural products inclusion as part of natural habits to prevent chronic illnesses...Fac. de FarmaciaTRUEunpu

Design and evaluation of novel electroconductive alginate hydrogels based on graphene oxide and reduced graphene oxide with applications in tissue engineering

193 p.El alginato es uno de los mejores biomateriales para la preparación de estos hidrogeles debido a sus excelentes propiedades, entre ellas su alta biocompatibilidad y facilidad de gelificación. Los hidrogeles de alginato han sido particularmente efectivos en la curación de heridas, administración de fármacos,terapias basadas en células y aplicaciones de ingeniería de tejidos. Estos hidrogeles a base de alginato conservan una estructura similar a las matrices extracelulares. Sin embargo, los hidrogeles de alginato tienen una adhesión celular deficiente, una resistencia mecánica débil y una liberación rápida del fármaco. Para compensar este inconveniente, muchos investigadores han incorporado diferentes materiales en la matriz de alginato para proporcionar soporte biomimético. El grafeno y sus derivados(óxido de grafeno y óxido de grafeno reducido) han demostrado ser candidatos adecuados para mejorarlas propiedades superficiales y la resistencia mecánica del alginate. Anteriormente observamos que GO,recubierto con suero bovino fetal (FBS) dentro de hidrogeles de alginato, mejora la viabilidad de los mioblastos incrustados. En la investigación actual, nuestro objetivo es estudiar varias proteínas,específicamente albúmina sérica bovina (BSA), colágeno tipo I y elastina, para discernir su impacto en la mejora observada previamente en mioblastos incrustados dentro de hidrogeles de alginato que contienenGO recubierto con FBS. Por lo tanto, describimos los mecanismos de formación de capas de proteína BSA, colágeno y elastina en la superficie GO y rGO. GO muestra una alta adsorción por BSA y elastina,mientras que rGO muestra una alta adsorción por colágeno. encontramos que la integración de GO y rGOdisminuye la impedancia y la capacitancia de GO y rGO. Además, describimos una mejor viabilidad celular y liberación de proteínas de las células incrustadas dentro de hidrogeles que contienen GOrecubierto de proteínas. Concluimos que estos hidrogeles híbridos podrían suponer un paso adelante en lamedicina regenerativ

A New Generation of Polymer/Ceramic Composite Biomaterials for Bone Regeneration

There is a substantial emerging interest for fundamental and applied research on the reinforcement of polymeric materials using nanotechnology. In the biomedical industry, development of novel bone cement composite materials with enhanced mechanical properties is of tremendous potential importance. The most universally used injectable bone cement is made of poly(methyl methacrylate) (PMMA); however, the major disadvantage of PMMA is its non-biodegradability. Polymers such as poly(propylene fumarate) (PPF) and polycaprolactone (PCL) are biodegradable, but suffer from a lack of mechanical properties. The aim of this research was to test the efficacy of these biodegradable polymers integrating nanotechnology for the development of composite biomaterials with improved mechanical properties sufficient for bone cements. This goal was investigated through a range of different studies. Focusing on nanostructured titania (n-TiO2) initially, titania nanofibers (n-TiO2 fibers) and nanowires (n-TiO2 wires) were introduced into a PPF matrix for potential use as an orthopaedic biomaterial to treat skeletal bone defects and diseases such as osteonecrosis. PPF was modified with maleic anhydride to provide functionality for the coordination of PPF to the surface of TiO2 nanofibers through a ring-opening reaction. The synthesis and modification of PPF were confirmed by NMR (1H and 13C) and XPS. The reaction chemistry of the functionalized PPF and nano-TiO2 was also investigated by XPS and FTIR analyses. The PPF-grafted nano-TiO2 was further employed in the development of bone cement composites by crosslinking/polymerization in the presence of N-vinyl pyrrolidone. Mechanical testing of the resulting bone cement composites demonstrated a significant enhancement of the tensile and flexural properties attributed to the chemical bonding between the PPF matrix and TiO2 nanofibers. On the basis of the determined mechanical properties, an optimum composition was found at 5 wt% loading of n-TiO2 fiber (0.5% in the starting composition) which provided a significant increase in Young’s modulus (153%), tensile strength (113%), flexural modulus (196%), and flexural strength (126%) when compared with the unfilled PPF. These improvements were attributed to the chemical linkage of the filler to the polymer matrix which enhances the transfer of a mechanical load to the n-TiO2 fiber, leading to an increase in the mechanical properties of the bone cement composite. Secondly, bone formation is an angiogenesis-dependent process, and the need for treatment modalities that enhance neovascularization is especially important for bone regeneration in necrotic bone. A bone cement system capable of delivering an angiogenic modulator in a controlled manner may have the ability to boost the angiogenic response when injected to an osteonecrotic lesion. Therefore, an angiogenic agent, ginsenoside Rg1, was incorporated into an orthopedic PPF-based cement. Additionally, Sr-doped TiO2 nanofibers synthesized in supercritical CO2 were added to the cement formulation as an alternative radiopacifier to enable visualization of the bone cement composites and potential monitoring of the healing and loosening processes. XPS analysis showed that Sr2+ was doped in the crystalline matrix of anatase with the formation of SrTiO3. The strong interfacial adhesion between PPF and nanofibers were characterized by SEM, FTIR, XPS, and thermal analyses and mechanical testing. The Sr-doped n-TiO2 fibers were shown to provide reasonably higher radiopacity to the PPF matrix, which is 0.32 ± 0.03 mm Al, than the unmodified fibers at the same loading level (0.20 ± 0.01 mm Al). In addition, bone cement composites loaded with ginsenoside Rg1 were found to provide a high drug release without sacrificing the mechanical properties of the bone cement. Furthermore, tube formation bioassays suggested that human umbilical vein endothelial cell lines would rearrange and align into a tubular structure in the presence of ginsenoside Rg1. Consequently, the proposed cement combines the immediate mechanical support given by the chemical bonding between the filler/polymer and optimum radiopacity (0.30 ± 0.12 mm Al) due to the incorporation of the Sr-doped TiO2 nanofibers to PPF matrix. Thirdly, because of the unique biological activities of ginsenoside Rg1, upregulating in vitro proliferation, migration, chemo-invasion, and tube formation in human umbilical vein endothelial cells (HUVECs), Rg1 can be incorporated into scaffold materials for bone tissue engineering applications. This incorporation could be achieved by encapsulation of ginsenoside Rg1 in biodegradable microspheres of PPF. Rg1-loaded PPF microspheres were prepared by both a double emulsion and a microfluidic technique for the first time in this research. The size and morphology of the Rg1-loaded PPF microspheres were characterized by SEM, showing unimodal 50-65 μm size diameters using the microfluidic technique, ideal for easy flowing powders required in commercial formulations. The PPF microspheres produced from the microfluidic technique gave high encapsulation efficiencies of up to 95.35 ± 0.82%, while those obtained from a conventional double emulsion method gave a much broader size distribution in the range of 2-45 μm with lower encapsulation efficiencies of 78.48 ± 1.68%. Release profiles were studied and quantified by UV-Vis spectrophotometry, with the results showing a lower initial burst in the release of Rg1 from the unimodal microspheres prepared by the microfluidic technique than from the double emulsion method. The burst effect was followed by a slow release profile which can be used for long term drug delivery applications to maintain the ginsenoside Rg1 concentration for an extended time period. Moreover, the released Rg1 showed a significant stimulatory effect on angiogenesis behavior and tube formation in human umbilical vein endothelial cells (HUVECs). Therefore, PPF microspheres developed in this study have potential for next-generation biomedical agents in drug-release devices for bone tissue engineering. Finally, the use of hydroxyapatite HAp is rather limited for heavy load-bearing applications due to low mechanical reliability and poor processability. Therefore, immobilization of a biocompatible metal/metal oxide on the surface of HAp has been receiving increased attention for applications involving the enhancement of mechanical properties of biocompatible prostheses. A novel nanostructured HAp and a composite of HAp and TiO2 with ultrafine structure and significantly improved mechanical properties were prepared using combined co-precipitation and sol-gel method in the green solvent, scCO2, and incorporated into polycaprolactone (PCL) matrix to develop scaffolds with enhanced physical and mechanical properties for bone regeneration. SEM and TEM analyses were employed to examine the morphology of the HAp nanoplates and HAp-TiO2 nanocomposites. The presence of Ti, O, Ca, and P in the HAp-TiO2 nanocomposites was detected by EDX. In addition, the effect of metal alkoxide concentration, reaction temperature, and pressure on the morphology, crystallinity, and surface area of the resulting nanostructured composites was examined using SEM, XRD, and the BET method. Chemical composition of the products were characterized using FTIR, XPS, and XANES analyses. TGA analysis was performed to investigate thermal behavior of the synthesized nanomaterials. Mechanical testing revealed a significant increase in the Young’s modulus (88.6%), tensile strength (122%), flexural modulus (47%), and flexural strength (59.6%) of PCL/HAp-TiO2 composites containing 20 wt % HAp-TiO2 compared to PCL/HAp composites

Glucose diffusivity in tissue engineering membranes and scaffolds: implications for hollow fibre membrane bioreactor

Unlike thin tissues (e.g., skin) which has been successfully grown, growing thick tissues (e.g., bone and muscle) still exhibit certain limitations due to lack of nutrients (e.g., glucose and oxygen) feeding on cells in extracapillary space (ECS) region, or also known as scaffold in an in vitro static culture. The transport of glucose and oxygen into the cells is depended solely on diffusion process which results in a condition where the cells are deprived of adequate glucose and oxygen supply. This condition is termed as hypoxia and leads to premature cell death. Hollow fibre membrane bioreactors (HFMBs) which operate under perfusive cell culture conditions, have been attempted to reduce the diffusion limitation problem. However, direct sampling of glucose and oxygen is almost impossible; hence noninvasive methods (e.g., mathematical models) have been developed in the past. These models have defined that the glucose diffusivity in cell culture medium (CCM) is similar to the diffusivity in water; thus, they do not represent precisely the nutrient transport processes occurring inside the HFMB. In this research, we define glucose as our nutrient specie due to its limited published information with regard to its diffusivity values, especially one that corresponds to cell/tissue engineering (TE) experiments. A series of well-defined diffusion experiments are carried out with TE materials of varying pore size and shapes imbibed in water and CCM, namely, cellulose nitrate (CN) membrane, polyvinylidene fluoride (PVDF) membrane, poly(L-lactide) (PLLA) scaffold, poly(caprolactone) (PCL) scaffold and collagen scaffold. A diffusion cell is constructed to study the diffusion of glucose across these materials. The glucose diffusion across cell-free membranes and scaffolds is investigated first where pore size distribution, porosity and tortuosity are determined and correlated to the effective diffusivity. As expected, the effective diffusivity increases correspondingly with the pore size of the materials. We also observe that the effective glucose diffusivity through the pores of these materials in CCM is smaller than in water. Next, we seeded human osteoblast cells (HOSTE85) on the scaffolds for a culture period of up to 3 weeks. Similar to the first series of the diffusion experiments, we have attempted to determine the effective glucose diffusivity through the pores of the scaffolds where cells have grown at 37°C. The results show that cell growth changes the morphological structure of the scaffolds, reducing the effective pore space which leads to reduced effective diffusivity. In addition, the self-diffusion of glucose in CCM and water has also been determined using a diaphragm cell method (DCM). The results have shown that the glucose diffusivity in CCM has significantly reduced in comparison to the water diffusivity which is due to the larger dynamic viscosity of CCM. The presence of other components and difference in fluid properties of CCM may also contribute to the decrease. We finally employ our experimentally deduced effective diffusivity and self-diffusivity values into a mathematical model based on the Krogh cylinder assumption. The glucose concentration is predicted to be the lowest near the bioreactor outlet, or in the scaffold region, hence this region becomes a location of interest. The governing transport equations are non-dimensionalised and solved numerically. The results shown offer an insight into pointing out the important parameters that should be considered when one wishes to develop and optimise the HFMB design

Novelty processing and smart delivery of Ganoderma Lucidum spores

In recent decades the traditional Chinese medicinal mushroom Ganoderma lucidum (GL), a fungal specie widely consumed homoeopathically in the Eastern Hemisphere, has been studied particularly with respect to antitumour and immunoenhancing effects. Research into the various claims however remains limited owing to the lack of quality and consistency across investigations. As such, efficacy and feasibility of scaleup has not been evaluated in a way that allows widespread consumption or approved treatment. This project tackles three aspects of drug development from Ganoderma lucidum: Biocompound extraction, healthcare evaluation via in-vitro testing, and encapsulation for smart delivery. These avenues are brought together for the first time to evaluate the prospects of developing GL for effective and safe healthcare. This research investigates the parameters that would influence the extractability of a biocompound from the spores of Ganoderma lucidum (GLS), via two conventional methods: Hot Water Extraction (HWE) and Ultrasound-Assisted Extraction (UAE). They are evaluated with respect to their crude water-soluble polysaccharide yield (GLPS). Solvent polarity and process duration were statistically significant factors affecting extract yield, with both extraction methods showing considerable gains over similar setups in literature, recovering over 6% crude GLPS using shorter durations and lower temperatures than other published investigations. This investigation highlighted the importance of solvent viscosity on specific DGlucan extraction in the GLPS yield. Bioactive effects of the extract were evaluated via cytotoxicity toward Human Osteosarcoma (HOS) cells in-vitro, achieving over 40% cell growth inhibition. Cytotoxicity however was only achieved when water-insoluble fractions were administered – suggesting cytotoxicity was a result of the unextracted crude triterpenoids (GLTP) containing Ganoderic Acids. Therefore, HOS-inhibitory capabilities are then compared to a GLPS extract containing Ganoderic Acids (in this work termed “PSGA”), extracted using HWE subject to supervised machine learning optimisation. As well as determining that this yield was maximised at the longest HWE duration and smallest solvent volume, it was observed to inhibit HOS growth by nearly 58% after 24 hours. Low doses and shorter incubation were most effective - suggesting concepts such as resistance (clonal selectivity) and delayed apoptosis, but further work will verify the reported effects of PSGA dosage and exposure time on cancer proliferation. Lastly, research effort is devoted to creating an alginate matrix for the controllable delivery of GLS using Electrohydrodynamic Atomisation (EHDA). Significant effects of the system’s process parameters on particle morphology are observed, in particular EHDA voltage. The carrier’s size, shape and surface features are correlated with its release profile. Importantly, GLS content (something traditionally compromised to maintain particle integrity) was maximised at 50 wt% whilst maintaining a controlled and spherical shape and size – making this study novel and extremely important. It is established that GLS-Alginate particles could offer controlled release over a 2-week administration in pH-neutral conditions; an environment not yet established as “stable” for alginate, yet reflective of physiological passage. Thus, for the first time sodium alginate is proven to be a real contender in controlling the delivery of GLS biomolecules. The reconciliation of these essential stages of drug development highlights some crucial points of focus as GL continues to undergo rigorous development in the realm of drug discovery

Advances in Nanogels

In the last two decades, nanogels have emerged as very promising and versatile biomaterials suitable for a wide range of applications. Their features, such as large surface areas, the ability to hold molecules, flexibility in their size and their water-based formulations, have earned them great recognition as drug delivery systems for various in vivo applications, confirming their potential. On the other hand, because of their tuneable and versatile characteristics, nanogels have been investigated in recent years for applications in various fields other than biomedicine. In view of this variety of possible applications of nanogels, in this Special Issue, we extend our knowledge on the topic of their possible uses described in literature, taking stock of the state-of-the-art for all possible nanogel applications and their synthesis methods