Gelatin Type Research Articles

Paper sizing with gelatine: from the macro- to the nano-scale

Gelatine sizing was used extensively for western papermaking before the nineteenth century and this technique is still applied nowadays for restoration purposes. Despite its wide use, the relationships between gelatine types, the strength of the size and its distribution inside the paper sheet are still unclear. Different concentrations of three gelatines of various origins and types (A/B) were used to size model papers. The gelatine uptake, the strength of the size and the presence of gelatine at the papers surface were investigated by using a water drop test method and ATR-FTIR spectroscopy. At a given concentration, similar uptakes were found for all gelatines but great variations were observed in terms of size strength and of gelatine ability to cover the surface of paper sheets. In addition, Scanning transmission X-ray microscopy was performed on paper fibres cross sections to map the distribution of the organic compounds (both cellulosic and proteinaceous) on a nanometer scale. This showed that gelatine coats but does not penetrate the fibres. It can be inferred that the different size strengths observed between the tested gelatines are mainly due to different ways of filling holes between fibres inside the paper mat, some gelatines being more prone to go inside the sheet than others which remain mostly distributed near the surface.

A review of gelatin: Properties, sources, process, applications, and commercialisation

This review begins with a discussion of the general properties of gelatin and its sources, particularly in the food and health industries, and then briefly address the status quo of gelatin in today's market. Apart from the basic chemical compounds and gelatin types, this paper also discussed the commercialisation of gelatin. This study also highlights the production of conventional gelatin and its current method of processing, i.e. enzymatic hydrolysis. In addition, the variety of raw materials of collagen is outlined and briefly broached the plant hydrocolloids which have been labeled as 'veggie-gelatin'. With regard to the potential and market stability of gelatin, its recent studies are summarised in this paper. Accordingly, this paper focuses on assessing the general utilities of the various sources of collagen as gelatin derivatives. At that basis, the aim of this review is to provide an insight into gelatin in current applications, market value and progress in gelatin extraction.

Influence of the span 80/Gelatin B combination on the formulation and stabilization of Argan oil-in-water emulsions

The present study aims to evaluate the effect of the combination of a linear protein: Gelatin type B and an oil-soluble emulsifier Span 80 (sorbitan monooleate) in the stabilization of argan oil-in-water emulsions. For this purpose, the emulsifiying properties of Gelatin itself with Argan oil as lipid phase were investigated first, by preparing oil-in-water (O/W) emulsions containing 10 wt%. Argan oil and varying Gelatin concentrations (0.5-2 % w/w), we have also formulated Argan O/W emulsions by span 80 alone at levels ranging from 1 to 6 wt%. Subsequentely, we explored the influence of the simultaneous application of the Span 80 and the gelatine on the stability properties and on the droplets size of Argan O/W emulsions, using different mixtures of the two emulsifiers. We compared the stability properties (flocculation, creaming, and phase separation) of argan O/W emulsions prepared with type B gelatine as the only emulsifier with those of emulsions prepared with span 80 and mixture of gelatin/Span. For stable emulsions, our analysis was completed with measurement of droplets size and Zeta Potential. Finally, all of the experimental results and the storage time showed that the emulsions prepared by 10 wt% argan oil and 2 (w/w) % Gelatin+ 3 wt% Span 80 were the most stable with optimum conditions for minimal creaming, small droplets size (size <1µm) and high net droplet charge (absolute value of ZP > 23). The presence of span 80 in coexistence with gelatin, even in small quantitiees, has a profound influence on the stability of the argan O/W emulsions.

Utilization of Sweet Potato in Development of Boba

Currently, boba phenomenon is extensively consumed by all generations from children to the elders. Boba which known as tapioca balls are originally made up of tapioca starch which then is served with milk tea. This sweet potato has lower calories than tapioca which can give benefits to the consumer since it has a lot of nutritional value such as high β-carotene, vitamin C, higher value of dietary fiber, higher antioxidants level and higher in protein content. Therefore, in this research this sweet potato flour were prepare in three sample which are sweet potato flour was substituted with 50% sweet potato flour and 50% tapioca flour, 100% sweet potato flour with added of two types of gelatine which are fish gelatine and bovine gelatine to make the boba pearls. This substitution will affect the physicochemical properties of the mixture such as pH and textural properties such as chewiness and energy needed to chew. As the results, the boba with fish gelatine has lower energy needed to chew which make it suitable for all level of generation which has chewiness value of 217.678±3.803 g with energy needed to chew is 4136.833±39.08382 g.%. With the growing of boba phenomenon, the findings from this study can help the consumers to continue consuming their favourite beverages will eating in healthy lifestyle.

Incorporation of gelatin improves toughness of collagen films with a homo-hierarchical structure

In this study, gelatin (type A and type B) with/without transglutaminase (TGase) were added to collagen fiber films to form hierarchical structure and its effects on the film were investigated. The analysis of mechanical properties indicate that gelatin significantly increased the toughness of the collagen film, where the 10 wt% type A gelatin -contained films had highest tensile strength, elongation at break and work of fracture. However, TGase crosslinking compromised the benefits of type A gelatin greatly, while type B gelatin showed a slight improvement, due to the difference in crosslinking activity between them. In the meantime, the hydrogen bonds were formed between the collagen and gelatin according to the results of the Fourier transformation infrared. In general, it is expected that the hierarchical structure formed in the collagen/gelatin films can be used as an effective strategy to enhance the collagen matrix films’ mechanical properties.

A Comparison of Two Gelatin Consolidants for the Preservation of Thermally Altered Skeletal Remains

A recent study (Topoleski & Christensen 2019) found that applying a food-grade gelatin solution to thermally altered skeletal remains resulted in significantly better structural preservation (reduced fragmentation) during recovery and transport compared to untreated controls. Here we expand upon this research and test whether a technical-grade gelatin would result in even better skeletal evidence preservation. Results show that bones treated with both the food-grade and technical-grade gelatins were better preserved (i.e., had less fragmentation) than untreated controls. Application of the technical-grade gelatin, however, did not result in significantly better preservation than the food-grade gelatin, and is less accessible, more expensive, and more difficult to prepare. Food-grade gelatin is therefore recommended, but other types of gelatins can be equally effective.

The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings

Bio-based coatings and release systems for pro-angiogenic growth factors are of interest to overcome insufficient vascularization and bio-integration of implants. This study compares different biopolymer-based coatings on polyethylene terephthalate (PET) membranes in terms of coating homogeneity and stability, coating thickness in the swollen state, endothelial cell adhesion, vascular endothelial growth factor (VEGF) release and pro-angiogenic properties. Coatings consisted of carbodiimide cross-linked gelatin type A (GelA), type B (GelB) or albumin (Alb), and heparin (Hep), or they consisted of radically cross-linked gelatin methacryloyl-acetyl (GM5A5) and heparin methacrylate (HepM5). We prepared films with thicknesses of 8–10 µm and found that all coatings were homogeneous after washing. All gelatin-based coatings enhanced the adhesion of primary human endothelial cells compared to the uncoated membrane. The VEGF release was tunable with the loading concentration and dependent on the isoelectric points and hydrophilicities of the biopolymers used for coating: GelA-Hep showed the highest releases, while releases were indistinguishable for GelB-Hep and Alb-Hep, and lowest for GM5A5-HepM5. Interestingly, not only the amount of VEGF released from the coatings determined whether angiogenesis was induced, but a combination of VEGF release, metabolic activity and adhesion of endothelial cells. VEGF releasing GelA-Hep and GelB-Hep coatings induced angiogenesis in a chorioallantoic membrane assay, so that these coatings should be considered for further in vivo testing.

Stability of hydrocolloid enriched oil-in-water emulsions in beverages subjected to thermal and nonthermal processing

Storage stability of concentrated oil-in-water beverage emulsions subjected to thermal and non-thermal processing was evaluated over 14 days at 22 °C. Emulsions were made with canola oil and aqueous dispersions of Type “A” and Type “B” gelatin and xanthan. They were also conjugated with propylene glycol alginate (PGA), modified starch and modified gum Arabic was studied at pH 3.4 and 7.0. Increase in apparent viscosity was observed with storage for gelatin Type “A” emulsions (pH 7.0) and gelatin Type “B” emulsions (pH 3.4). All emulsions showed shear-thinning behavior associated with droplet flocculation. Increase in the slope of particle size distribution was more obvious for protein (gelatin) stabilized emulsions. Concentrated gelatin Type “A”-modified starch had smaller particle size and greater stability at pH 3.4, followed by gelatin Type “B”-modified starch and gelatin Type “B”-xanthan-PGA both at pH 7.0. Simulated orange beverage (pH 3.0) and dairy beverage (pH 6.8) using stabilized emulsions were pasteurized by heat and high pressure. Emulsions formulated by modified starch produced better stability in both beverage types. Gelatin Type “A” and modified starch conjugate resulted in greater stability compared to other conjugated emulsions. However, gelatin alone failed to stabilize the emulsion systems. The ringing was characteristically associated with emulsions formed with gelatin alone. Neither thermal processing nor high-pressure treatment resulted in destabilization of emulsions.

Exploring the Properties of Pineapple Leaf Fiber and Prosopis Julifora Powder Reinforced Epoxy Composite

ABSTRACT Natural fibers derived from plants are gaining attraction for its low-cost production, excellent mechanical properties, eco-friendly nature and availability. They act as an effective replacement of synthetic materials, makes them suitable for industrial applications. In this work, natural fiber derived from the Pineapple leaf fiber (PLF) and powder derived from Prosopis Juliflora (PJP) plant as the filler was utilized as an effective reinforcement for polymer matrix composites. PLF has high cellulose content, makes it suitable for the achievement of high tensile strength, whereas the porous nature of the fiber surface enhances bonding with the polymer matrix. The low cost and wide availability of the fibers make it a suitable alternative for the harmful synthetic fibers. Semi-crystallinity of the fiber allows reduction in water absorption. The PJF belonged to gelatinous or mucilaginous type. PLF was chemically treated with NaOH to remove the wax content on the surface and to improve its mechanical properties. Composites were fabricated by using compression molding machine with 30 weight percentage (wt.%) of untreated PLF and PJP, 30 wt.% of treated PLF and PJP, 40 wt.% of treated PLF and PJP, 50 wt.% of treated PLF and PJP. The remaining wt.% attributes to the epoxy matrix addition. In the fiber wt.%, equal weights of PLF & PJP were taken. The untreated and treated fiber composite samples are tested for their tensile, impact and flexural strength. SEM images of the PLF, PJP and mechanical tested samples were analyzed. Water absorptivity test was carried out to identify the absorption level of fibers in the composite. The test results suggest that the Pineapple leaf fiber and Prosopis Julifora powder reinforced epoxy reinforced composites would be a low-weight, low cost and higher strength material appropriate for industrial applications.

Physico-Chemical Characteristics of Giant Featherback (Chitala lopis) and Mackerel (Scomberomorus commerson) Bone Gelatins and Their Potential as Gelling agents in Gel Mixtures for Roselle (Hibiscus sabdariffa L.) Soft Jelly Candies

The gel strength of gelatin depends on its raw material. Fish gelatin shows a broad range of gel strengths. Giant featherback and mackerel bone gelatins have the gel strengths 220 and 38 Bloom, respectively. Here, we prepared roselle soft jelly candy using the single gelatin and mixtures gelatins from bovine, giant featherback, and mackerel sources. Roselle calyces extract has been used as a food additive to improve taste, aroma, and antioxidant content. The soft jelly candies (1.5 % w/v roselle extract and 12 % gelling agent) were prepared using three types of gelatin (giant featherback (GF), mackerel (M), and bovine (B)) in four mixtures (GF:B = 1:3, GF:B = 1:1, M:B = 1:3, and M:B = 1:1). This experiment was arranged in a completely randomized design with three replications for each treatment. Physico-chemical and sensory characteristics of the jelly candies were determined. The data were analyzed by ANOVA continued by the LSD test. The results showed that water content, pH, gel strength, hardness, rigidity, and hedonic quality (taste, color, texture, and overall performance) of the roselle soft jelly candies were affected by choice of gelatin, but not total reducing sugar. Roselle soft jelly candy made with giant featherback and bovine gelatin (1:3) mix was the most preferred by the panelists.

Tunable physical and mechanical properties of gelatin hydrogel after transglutaminase crosslinking on two gelatin types

The crosslinking and related gel properties of 3 wt% gelatin (type-A and type-B) catalyzed by microbial transglutaminase (MTG, dose of 0–20 U/g gelatin) have been investigated. A MTG-depended increase in the molecular weight and mean diameter of both gelatins was observed, where type-A presented a higher crosslinking efficiency than type-B due to more acyl donors of the former. As MTG concentration increased, the surface hydrophobicity and thermal stability of type-A gelatin increased. Textural profile analysis (TPA) of type-A gelatin hydrogel showed a decrease in hardness and slight increase in springiness, while type-B gelatin gel was not affected generally. Rheological measurements confirmed the melting point of type-A gelatin hydrogel continually increased until the disappearance of gel thermo-reversibility at higher MTG levels (≥12 U/g gelatin), while type-B gelatin hydrogel always showed a sol-gel transition, suggesting that the gel performance was depended on the dominance of whether physical crosslinking or chemical crosslinking. Scanning electron microscope (SEM) results showed that the network structure of the type-A gelatin became more irregular as MTG increasing which indicated that introducing additional covalent cross-links within or between gelatin chains had a profound influence on gel's network structure, closely associated with the gel properties mentioned above. In summary, the superiority of type-A in MTG-crosslinking efficiency than type-B, can be used to modulate the physical and mechanical properties of gelatin hydrogel, governing by the combing of weak physical crosslinking and strong covalent crosslinking, which will be suitable for numerous industrial applications.

Microstructure and characteristic properties of dogfish skin gelatin gels prepared by freeze/spray-drying methods

The effects of two pretreatments (microwaves or oven-drying) on the dogfish (Squalus acanthias) skin as well as two drying processes (freeze-drying or spray-drying) on the extracted gelatins were studied. Thus six types of gelatins were obtained, three of which were freeze-dried (FG) and the others were spray-dried (SG), from the untreated skin (US), microwaves-pretreated skin (MS) and oven-pretreated skin (OS). The highest yield (8.67%) was obtained for the OSFG, while the lowest one (3.06%) was measured for the OSSG. Interestingly, all gelatins exhibited relatively high protein (84.02–89.53%), and low lipid (0.50–1.71%) and ash (3.05–7.17%) contents. In addition, gelatins were analyzed by the Fourier transform infrared and the spectra displayed important differences in some specific peaks, particularly in the amide I, amide II and amide III. The gelatins extracted from the untreated skin, regardless the drying method, presented the highest foaming capacity. The textural profile analysis showed that USSG was the hardest (213.6 g) and the chewier (23.8 N × mm) gelatin. Moreover, analysis of thermal properties showed that USSG also has the highest glass-transition temperature. The interesting properties of gelatin extracted from dogfish skin encourage their future use as a functional ingredient in industrial food formulations.

The Mechanical Properties of Mimic Skin

This paper focuses on the characterized of the mechanical properties and hyper elastic behavior of lab made skin. Bovine Serum Albumin (BSA) combined with gelatin as a base. BSA is a plasma lead concentrations or heparin plasma which is separated from blood sample and it is not associated with significant changes in iron or hemoglobin concentrations. In general, the gelatin is widely used as the best material for skin substitution since it exhibits the characteristic of human skin. However, the lab made skin layer was made of non-halal type gelatin (Type B). The methodology process started by adding the BSA and using the type A gelatin to carry out the mechanical properties and hy-per elastic behavior of halal lab made skin layer. A uniaxial tensile test standard that being used in this study is ASTM D412. The raw data (Load-Extension) from computational was plotted on graph stress-strain. The numerical approach such as Mooney-Rivlin model and Yeoh’s model were selected to analyze a stress-stretch of composition gelatin and BSA. From the results Mooney-Rivlin model, the con-stant, C1 is in the range of (0.0187-0.0658) MPa and C2 is in the range of (0.0628-0.0737) MPa. Meanwhile the constant, CP for Yeoh model is in the range of (0.0748-0.0861) MPa. As a conclusion, the composition of gelatin and Bovine Serum Albumin is a best combina-tion as it increases the strength of the lab made skin layer. Therefore, the most suitable composition is 10 wt.% of gelatin and Bovine Serum Albumin.

Gelatin/Whey Protein- Potato Flour Bioplastics: Fabrication and Evaluation

This research utilized three animal proteins which are whey protein isolate (Wh) and two types of gelatin, including bovine gelatin (BG) and chicken gelatin (CG) from bovine shin bones and chicken feet respectively, to improve the mechanical properties of whole potato flour bioplastics. The goal is the development and characterization of eco-friendly bioplastic sheets by employing the compression molding method. The tensile, DMTA, FTIR and TGA characteristics of the blending bioplastics were compared with bioplastic made from whole potato flour as control. Results showed that protein treatments greatly enhanced the tensile strength (at least 2 times), tan δ (up to twice) and elongation at break (3 to 11 times). Furthermore, the thermal stability of studied bioplastics does not differ up to 200 °C. Among the blending bioplastics, the BG bioplastic had the highest tensile strength (5.67 MPa) and CG bioplastic had the highest elongation at break (20.50%). Meanwhile, the investigation of functional groups using Fourier-transform infrared spectroscopy (FTIR) confirmed better molecular interactions in the blending bioplastics. This research shows the feasibility of producing animal protein‐potato flour biodegradable edible bioplastic materials with different properties and, consequently, different applications, which contribute to adding a high value to different byproducts from the livestock/poultry industries.

Quality Risk Management and Quality by Design for the Development of Diclofenac Sodium Intra-articular Gelatin Microspheres.

The aim of the present study was to evaluate the development of an intra-articular nonsteroidal anti-inflammatory drug gelatin microsphere formulation based on quality risk management and quality by design approaches. Specifically, after setting the quality target product profile and the critical quality attributes, risk assessment was performed by constructing Ishikawa fishbone diagrams based on preliminary hazard analysis. A Plackett-Burman screening experimental design was applied in order to identify the factors (previously classified by risk assessment analysis as having high risk of failure) having a statistically significant impact on the formation of gelatin microspheres. Particle size, polydispersity index, and drug loading were used as responses, while diclofenac sodium was selected as a model drug. All drug-loaded gelatin microspheres were prepared by emulsion-crosslinking process. Screening results showed that gelatin type, surfactant type and quantity, oil phase type, emulsification speed, and glutaraldehyde's concentration had a statistically significant impact on microsphere's final and intermediate critical quality attributes. A design space was then constructed based on central composite design overlaying contour plots, while verification experiments for the optimum suggested formulation (derived from a set control strategy) showed good agreement between the predicted and the experimentally observed results. In addition, the physicochemical characterization of the optimum formulation showed the formation of significant molecular interactions between the drug and the gelatin matrix, leading to the complete amorphization of diclofenac within the microsphere structure, while dissolution release experiments showed a biphasic release profile which extended the drug's release for up to 30days, governed by a Fickian diffusion release mechanism.

Improved Diabetic Wound Healing by EGF Encapsulation in Gelatin-Alginate Coacervates.

Topical imageplication of epidermal growth fctor (EGF) has been used to accelerate diabetic foot ulcers but with limited efficacy. In this study, we selected a complex coacervate (EGF-Coa) composed of the low molecular weight gelatin type A and sodium alginate as a novel delivery system for EGF, based on encapsulation efficiency and protection of EGF from protease. EGF-Coa enhanced in vitro migration of keratinocytes and accelerated wound healing in streptozotocin-induced diabetic mice with increased granulation and re-epithelialization. While diabetic wound sites without treatment showed downward growth of hyperproliferative epidermis along the wound edges with poor matrix formation, EGF-Coa treatment recovered horizontal migration of epidermis over the newly deposited dermal matrix. EGF-Coa treatment also resulted in reduced levels of proinflammatory cytokines IL-1, IL-6, and THF-α. Freeze-dried coacervates packaged in aluminum pouches were stable for up to 4 months at 4 and 25 °C in terms of appearance, purity by RP-HPLC, and in vitro release profiles. There were significant physical and chemical changes in relative humidity above 33% or at 37 °C, suggesting the requirement for moisture-proof packaging and cold chain storage for long term stability. We propose low molecular weight gelatin type A and sodium alginate (LWGA-SA) coacervates as a novel EGF delivery system with enhanced efficacy for chronic wounds.

In vitro response of mesenchymal stromal cells and peripheral blood mononuclear cells to high- and low-endotoxin gelatine methacryloyl hydrogels

Purpose: Gelatin methacrylol (GelMA) hydrogels are widely used for cartilage regeneration. There are many types of GelMAs and gelatins commercially available, but their exact endotoxin content is often not stated. Endotoxins and other pro-inflammatory factors are known to influence cartilage health and repair. Unravelling the impact of such endotoxin content can help understand if these materials are suitable for regenerative purposes. It also poses the question whether in vitro Results obtained with endotoxin containing hydrogels can be translated to the clinic.

Effect of utilization of alternative hydrocolloid-based stabilizers on rheology of oil-in-water beverage emulsions

In this study, effect of using alternative stabilizers based on protein (gelatin ‘A’ and type ‘B’) and polysaccharide hydrocolloids [modified starch and modified gum Arabic (MGA)] was studied using rheological properties of concentrated oil-in-water beverage emulsions. Emulsions were prepared adding 10 g/100 g canola oil into hydrated solutions of 1 g/100 g and 0.75 g/100 g gelatin (type ‘A’ and type ‘B’), and 6 g/100 g and 12 g/100 g modified starch and MGA in buffer solutions at pH 3.4 and 7.0. The choice of pH was based on mimicking acidic fruit-based beverages (pH 3.4) and dairy/milk beverage emulsions (pH 7.0). Emulsions stabilized with gelatin “A” showed a lower flow behavior index (n = 0.85) as compared to gelatin “B” at pH 7.0. However, for polysaccharides stabilized emulsions, unlike protein stabilized emulsions, only slight changes in viscosity and flow behavior indices were noted at elected concentrations. Gelatin stabilized emulsions were more susceptible to pH than modified starch and MGA stabilized emulsions. Gelatin type ‘A’ possessed greater shear thinning features at high pH and showed Newtonian behavior at acidic pH unlike Gelatin type ‘B’ which showed shear thinning behavior at pH 3.4.

Gelatin nanoparticles for NSAID systemic administration: Quality by design and artificial neural networks implementation.

The present study evaluates the preparation of systemic administrated NSAID gelatin nanoparticles with the aid of quality by design and artificial neural networks (ANNs). Specifically, two different preparation techniques (i.e. nanoprecipitation and two-step desolvation) were implemented for the formulation of diclofenac sodium (DLC) gelatin nanoparticles (GNs). Preliminary screening experiments showed that in the case of nanoprecipitation the best compromise (in terms of achieving both small particle size and high encapsulation efficiency) was the use of poloxamer 407 (as stabilizer) and acetone (as non-solvent), while in the case of two-step desolvation significant effect had the use of acetone, gelatin type and bloom number (type B with bloom 150 was selected for further evaluation). Implementation of a central composite experimental design (CCD), showed that in the case of nanoprecipitation the optimum formulation can be achieved at high poloxamer, high gelatin and moderate to high glutaraldehyde (GTA used for crosslinking) concentrations, while in the case of two-step desolvation high gelatin and GTA concentrations are needed. Artificial neural networks (ANN) implementation showed significantly improved prediction ability compared to MLR, while verification experiments showed good agreement between the ANN predicted and the experimentally obtained results. SEM analysis of the optimum suggested formulations showed nanoparticles with smooth surface, while powder X-ray diffraction (XRD) analysis showed the formation of amorphously dispersed systems, and Fourier transform infrared spectroscopy (FTIR) revealed the presence of molecular interactions irrespectively of the preparation method followed. A slightly faster release profile was observed in the case of nanoprecipitation based GNs, while all formulations followed biphasic release profile.

Ultra-Small Size Gelatin Nanogel as a Blood Brain Barrier Impermeable Contrast Agent for Magnetic Resonance Imaging

Magnetic Resonance Imaging (MRI) contrast agents with rapid renal excretion that do not penetrate the blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCFB) are preferred for safer and low-risk diagnosis. Gadolinium (Gd)-conjugated nanoparticles have been proposed for use as such contrast agents; however, the particle size must range between 1 to 7 nm to ensure rapid renal excretion. In this study, three types of gelatin, dissolved in water at varying concentrations of 0.1–2 wt.%, were irradiated with 5 kGy γ-rays at 25 °C under aerated conditions to produce ultra-small gelatin nanogels having an average particle size ranging between 5.5 ± 1.9 to 21 ± 3.7 nm. Ultra-small Gd-coordinated gelatin nanogels (GdGN) suitable for use as MRI contrast agents were produced using 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid mono- N -hydroxysuccinimide ester (DOTA-NHS) and DOTA-butylamine as Gd ligand derivatives. Non-cytotoxicity and effective relaxivity of GdGN as a positive MRI contrast agent were verified using in vivo experiments. Rapid renal excretion of GdGN was observed in mice within 1 h with no accumulation in the liver. GdGN did not migrate across the BCFB in normal mice, thus emphasizing its safety as an MRI contrast agent.