Controlled Release Technology Research Articles

Encapsulation of fluazinam to extend efficacy duration in controlling Botrytis cinerea on cucumber.

Fluazinam is an effective fungicide in controlling gray mold, but has short duration of efficacy. Increasing application dosage may cause phytotoxicity. To overcome this shortage, a controlled-release technology was studied by encapsulating fluazinam. Ethyl cellulose polymer microcapsules were loaded with fluazinam to formulate a fluazinam capsule suspension (FCS). The efficacy for inhibition of B. cinerea and persistency of the FCS were examined by comparing with fluazinam technical concentrate (FTC) and aqueous fluazinam suspension concentrate (FSC) using microscopic observation and high-performance liquid chromatography analysis. FCS formed capsules, with median size of 3.17 μm in diameter, had 82.3% encapsulation efficiency. It had a stronger inhibitory activity against B. cinerea than FTC and FSC measured 7 days after the treatments. The half-life of FCS on cucumber leaves was 3.4 days, longer than the 2.3 days of FSC. FCS formulation significantly improved the inhibition of B. cinerea and resulted in prolonged and sustained release. Moreover, microencapsulation increased the duration of the efficacy of fluazinam on target crops. This formulation could help to sustain pesticides and protect the environment. © 2021 Society of Chemical Industry.

\u03b9-Carrageenan nanocomposites for enhanced stability and oral bioavailability of curcumin

BackgroundCarrageenan (CRN), a polygalactan consisting of 15 to 40% ester sulfate, is used in oral controlled-release technology due to its viscosity and large molecular weight. Curcumin (Cur) is a highly potent antioxidant and anti-inflammatory agent against various diseases, such as tumors, liver disease, rheumatism, and Alzheimer’s disease. Although Cur shows excellent effects in the body, it has major problems, such as poor solubility and low bioavailability in water.MethodNanocomposites containing Cur were developed by emulsion technique. Cur@CRN was characterized through the viscosity measurement, size analysis, stability test, and loading efficiency. Antioxidant effects was analyzed with DPPH reagent, and anti-inflammatory effects was analyzed by NFkB/IkBr signaling pathway with wester blot. Cellular interaction was confirmed by flow cytometry and confocal images. Especially, permeability test was demonstrated in MDCK and Caco-2 monolayer cells.ResultsCur@CRN enhanced stability, antioxidant, and anti-inflammatory effects in vitro, compared with other polymer nanocomposites. Sulfate groups (SO42−) in CRN are transported across cell membranes by anion exchangers of the SLC26 gene families. We confirmed Caco-2 cells expressed SLC26A2 receptors interacted with CRN, expect for Tween 80 and hydroxypropyl cellulose. In contrary, other cells did not interact with CRN due to non-expression of SLC26A2 receptors. Based on this, Cur@CRN showed 44-fold better permeability than free Cur in MDCK cell assay.ConclusionEnhanced intestinal permeability of Cur can be applied in various health care facilities with significant antioxidant and anti-inflammatory effects compared with nonformulated Cur. Since the CRN composed of nanocomposites has a high molecular weight, high viscosity, and sulfate groups, it will be a platform that can increase the bioavailability of various insoluble drugs as well as Cur.

Passing the torch of the Journal of Biomedical Materials Research—Part A

The field of biomaterials science is a constant wonder, with the advent or application of new chemistries; novel methods to characterize biomaterials in unprecedented resolution; and exciting applications of existing, composite, or innovative biomaterials to biomedical problems. The journal will continue to publish original contributions concerning studies of the preparation, performance, and evaluation of biomaterials and the response of blood and tissues to biomaterials. In addition, interdisciplinary areas are covered, such as tissue engineering, medical devices, and controlled release technology where biomaterials play a significant role. We welcome high-quality submissions by investigators throughout the world who are making exciting advancements in these areas. The journal will also continue to publish award-winning papers selected annually by SFB, as well as timely and critical review articles. Over the last several years, the publication landscape for biomaterials research has grown substantially and provides many opportunities to publish one's work. Such decisions are made for many reasons, including the publication process, perceptions of journal impact, alignment with a professional society, turnaround time for decision, ability to effectively reach one's target audience, and visibility of the work. As the official journal of the SFB, I aim to ensure that JBMR Part A is at the top of every author's list when considering where to submit their best work. We can accomplish this by (a) identifying, inviting, and accepting high quality work; (b) publishing articles that are of wide interest; and (c) increasing the visibility and contributions of accepted articles. We have identified a collection of new Associate Editors, representing the breadth of research within our discipline. Along with myself, these individuals will be tasked with managing the review process closely in order to ensure the quality and rigor of submissions and accelerate our time to first decision. It is my goal that all submissions to the journal receive a first decision in less than 1 month. Furthermore, we have empowered Associate Editors to personally solicit submissions at scientific meetings and to also reach decisions based on their own evaluation of submissions. We need to continue striving to decrease turnaround time, increase diversity of submissions, and ensure that only high-quality papers are published. It is imperative that we accelerate publication if we are to elevate the journal to the highest level. In addition, we will use social media and other platforms to highlight the publication of new work in the journal and amplify its reach throughout the community. I will regularly evaluate the composition of our Editorial Board to ensure its involvement in our mission. Participation on our Editorial Board is an honor and recognition of great accomplishments in our discipline, and I will leverage this expertise in several ways. I will call upon the Board for advice and suggestions to continually improve all aspects of the journal. Members of the Board will be asked to evaluate papers in a timely manner. Emerging initiatives will include a reviewer mentoring program to provide personal training on best practices for reviewing papers in the journal, where trainees will be selected and matched with members of the Board. This will provide an opportunity to enhance reviewer expertise and build a connection between trainees and the journal as a preferred target for submitting manuscripts. These initiatives will empower the Board to have a lasting, positive influence on the future of the journal. Such a venture requires the participation of many individuals. Our publisher Wiley is continually working to streamline the submission process to make the submission of your manuscript faster and more efficient. Our Associate Editors and Editorial Board work hard in this largely volunteer effort because of their commitment to our discipline. Our scientific community should submit our best work to JBMR Part A and say “yes” when asked to serve as reviewers. Your reviews should be thoughtful, accurate, and returned in a timely manner to improve the quality of the work and shorten the review time. We must continue to improve the quality of work published in our journal through critical discussions at annual meetings, effective reviews of submitted papers, and referencing papers from our journal in other publications. I look forward to representing our societies and discipline in this important role and partnering with Wiley Publishing to expand the reach of our journal around the globe. It is an exciting time in our field. Please embrace the JBMR Part A and help us reach the heights that our journal deserves. Onward and upward! Kent

A mathematical model for pH-responsive ionically crosslinked TEMPO nanocellulose hydrogel design in drug delivery systems

Ionically crosslinked hydrogels based on TEMPO nanocelullose and alginate were prepared to develop a generalized pH value, temperature and biopolymer concentration dependent mathematical model. The distinctive attention was in the demonstration of hydrogen bonds effects in the mathematical model, prevailing especially in the field of low crosslink densities of TEMPO nanocellulose hydrogel in acid medium. Accordingly, alginate hydrogels were subjected to the research as comparable samples with less significant hydrogel bonds effect. The equation was built upon the determination of the average mesh size in a TEMPO nanocellulose and alginate hydrogel network and studying its changes in different pH release environments. Based on rheological measurements of TEMPO nanocellulose and alginate from the basic and acidic release environment, the mechanism of swelling and shrinkage was thoroughly discussed as well as the influence of substituent groups, ionic interactions and hydrogen bonds in different pH medium were evaluated. Due to the protonation of carboxylic groups, TEMPO nanocellulose and alginate hydrogels shrink in an acid environment. The presented approach will accelerate, improve and reduce the cost of research in the field of controlled release technology with target drug delivery.

Application of imidacloprid controlled-release granules to enhance the utilization rate and control wheat aphid on winter wheat

During winter wheat production, aphids need to be controlled with pesticides for the entire growth period. Controlled-release technology has been regarded as an alternative method for the improvement of pesticide efficiency. This study investigated two types of imidacloprid controlled-release granule (CR-GR): 2% imidacloprid CR-GR and 0.2% imidacloprid pesticide-fertilizer controlled-release granule (PF-CR-GR) when wheat was sown in winter. The release performance, utilization rate, terminal residues in edible parts, control effect on aphids, and achieved winter wheat yield were evaluated for both laboratory experiments and field application. Imidacloprid PF-CR-GR released more quickly in aqueous medium than CR-GR because of its good water solubility. After CR-GR treatments, the concentrations in wheat roots and soil were similar throughout the entire sampling period, and the concentrations in shoots were about 10–20% of those in roots. Imidacloprid was better absorbed when CR-GR was used as root treatment, compared with foliar treatment. Field application showed that imidacloprid CR-GR and PF-CR-GR controlled aphids throughout the entire growth period of winter wheat and improved the wheat yield. These findings identified application of imidacloprid CR-GR and PF-CR-GR on winter wheat as an effective way to enhance the pesticide utilization rate and ensure adequate yield. This paper provides a theoretical basis for the scientific use of pesticides and guides scientific pesticide application.

In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations.

Drug controlled release technologies (DCRTs) represent an opportunity for designing new therapies. Main objectives are dose number optimization and secondary effects reduction to improve the level of patient/client acceptance. The present work studies DCRTs based in blended polymeric implants for single dose and long-term therapies of florfenicol (FF), a broad spectrum antibiotic. Polymers used were PLGA and Eudragit E100/S100 types. Eudragit/PLGA and FF/PLGA ratios were the main studied factors in terms of encapsulation efficiencies (EEs) and drug release profiles. In addition, morphological and physicochemical characterization were carried out. EEs were of 50-100% depending on formulation composition, and the FF releasing rate was increased or diminished when E100 or S100 were added, respectively. PLGA hydrolytic cleavage products possibly affect Eudragit solubility and matrix stability. Different mathematical models were used for better understanding and simulating release processes. Implants maintained the antimicrobial activity against Pseudomonas aeruginosa up to 12 days on agar plates. The developed DCRTs represents a suitable alternative for florfenicol long-term therapies.

The mutual effect of the crosslinker and biopolymer concentration on the desired hydrogel properties

Controlled release technology has a great potential in pharmaceutical and medical applications to ensure high efficacy of treatment, reduces the aggressive action of the medicines per patient, decreases the cost of treatment and reduces the side effects of the drug as well. In this research, hydrogels from biopolymers were designed for potential use in the drug release systems. The main objective was the manipulation of alginate and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) - oxidized cellulose nanofibers hydrogels crosslinking density by changing the biopolymer and crosslinker concentrations. Rheological measurements of prepared hydrogels were performed to determine the viscosity as a biomedical applicability factor and for determining shear modulus as a basis for theoretical mesh size calculations. The homogeneity of the hydrogel was confirmed by NMR verifying the validity of the mesh size calculations at the same time. In the last stage, the improved mathematical model was developed taking into account the concentration of crosslinker and the concentration of biopolymer in hydrogel as well. The designed model is the first step for the preparation of hydrogels with specific properties.

Preparation of natural pyrethrum-polylactic acid microspheres with different particle sizes and surface morphology

Controlled-release technology has been widely studied in the field of medicine, but it is rarely used in pesticides. The objective of this study was to obtain pyrethrin-polylactic acid microspheres with different particle sizes and morphologies. By adjusting the concentration of polylactic acid and the rotation speed, a series of microspheres can be prepared simply and efficiently by using the single emulsion-solvent evaporation method. The result of laser particle size analyzer showed that the average diameter of the microspheres ranged from 13.5 to 142.4 μm. The FESEM observation revealed that the obtained microspheres were spherical with pores on the surface. And as the particle size decreases, the area of the surface pores becomes larger and shallower. The spectrum of FTIR indicated the presence of pyrethrin in the prepared microspheres.

Advanced nursing recovery therapy in the field of nanotechnology based on tetracycline hydrochloride type drugs

With the development of wound care theory and practice methods, the development of new materials and the improvement of sustained release and controlled release technologies, medical dressings will develop in the direction of multi-functionality, diversification and intelligence. This has also promoted the development of clinical care, better service for wound patients, new dressings, and new methods for wound care. Among many new dressings, nanotechnology-based polymer nanogels have good application prospects due to their good water retention properties and micelle stability properties. At present, a large number of researchers have developed a variety of wound care materials, which are widely used in clinical settings. However, due to the shape of the material or its characteristics, the mechanism of action of many materials has not been studied in detail. How to prepare a new type of wound dressing, which has multiple functions - integrating haemostasis, bacteriostatic, stimulating cell division and differentiation, accelerating tissue healing, moisturising and phlegm, etc., so as to achieve a good evaluation of patients' post-care recovery is. China's long-standing and urgent problem in the medical device market. Therefore, this study used the tetracycline hydrochloride drug doxycycline as an antibiotic drug for nano-modified dressings. Under the theoretical guidance of the interaction between wound healing and pH of microenvironment, a polyethylene glycol (PEG) modified PEG-doxycycline hydrogel nanocomposite dressing was prepared to study the stability of nanoparticles in the dressing. Physical and pH responsiveness, swelling behaviour of composite dressings, and physicochemical properties of drug release behaviour were studied. At the same time, in order to study the effect of the PEG-doxycycline nanocomposite hydrogel on the recovery of wound care in patients, this study applied the composite nano dressing to the clinic. Through the comparative study of patients' quality of life, wound healing, nursing satisfaction and treatment effect, the innovative application of tetracycline hydrochloride in the recovery of wound care of patients under nanotechnology is realised. The results of this study indicate that PEG-doxycycline nanocomposite hydrogel prepared under the guidance of nanotechnology can promote wound healing, shorten hospital stay and reduce complications. At the same time, the use of the dressing can also reduce the work of nursing, alleviate the suffering of the patient, improve the comfort of the patient, and greatly improve the nursing effect and effect on the patient. This has certain promotion and research value for the implementation of continuous nursing methods for patients with chronic wounds, which can be popularised in clinical practice.

Encapsulation of Food Components and Bioactive Ingredients and Targeted Release

The potential utilization of encapsulation techniques in food, pharmaceutical and agricultural products preparation, presents a new alternative for complementary technologies such as targeting delivery vehicles and carriers for active food ingredients. Encapsulation could be accomplished by different techniques like: simple or complex coacervation, emulsification technique, phase separation, spray drying, spray chilling or spray cooling, extrusion coating, freeze drying, fluidized-bed coating, liposomal entrapment, centrifugal suspension separation, co-crystallization and molecular inclusion complexation. Encapsulation is a method by which one bioactive material or mixture of materials is coated by the other material. It is designed for protection, isolation, assists in the storage and controlled release. A timely and targeted release improves the effectiveness of ingredients, broadens the application and ensures optimal dosage, thereby improving cost-effectiveness process for manufacturers. This review highlights recent innovations in encapsulation and controlled release technologies. In addition, design principle of novel peppermint oil delivery systems which displays the new structured biomaterials for capsules fabrication by complex coacervation technique, besides microemulsification method for bioactive material, Lactobacillus encapsulation and targeted release studies reported.

New polymeric molluscicide-attractant (niclosamide-l-glutamate) for control of Biomphalaria alexandrina

Controlled-release technology was introduced to offer an incredible guarantee for improving the adequacy of the existing active molecules and solving the related environmental troubles. Our study attempts to utilize the controlled release of alginate niclosamide-l-glutamate formulation to control Schistosoma mansoni intermediate host (Biomphalaria alexandrina snail) and to evaluate the amount of niclosamide released in relation to its attraction and mortality rate. Results: polymeric formulations B3-4b at a concentration of 0.3 ppm niclosamide in combination with 75% l-glutamate caused 100% mortality of B. alexandrina snails 5-day post-exposure. Stable snails mortality rates were obtained post-exposure to polymer B3-4a (R2 = 0.9823). The high potential of the polymeric formulations B3-4a (0.2 ppm niclosamide and 75% l-glutamate) to attract snail toward polymer direction was manifested by 80%, 14%, 6% and 0% snail in areas (I), (II), (III) and (IV), respectively 24-hr post-exposure. While, B3-4a showed a high mortality rate of attracted snails resembled by 40% and 100% on the 2nd and 7th days, respectively. The modified structure of polymer-niclosamide-l-glutamate prolonged the validity and efficiency of the niclosamide. Slowly released molluscicide was effective at lower concentrations with increasing concentrations of the applied attractant that could reduce its toxicity to the water ecosystem.

Research Progress on Controlled Release Technology for Insect Pheromones

Research Progress on Controlled Release Technology for Insect Pheromones

Drugs adsorption and release behavior of collagen/bacterial cellulose porous microspheres

A porous microsphere with good biocompatibility was fabricated based on collagen (COL) and bacterial cellulose (BC). The adsorption and release behaviors of the COL/BC porous microspheres were studied using BSA as the model protein, and employing quasi-primary, quasi-secondary, and Kannan-Sundaram intragranular diffusion models, zero-order, first-order, Higuchi and Korsmeyer-Peppas models. The results showed that the COL/BC porous microspheres are beneficial to the proliferation of MC3T3 E1-cells. The linear Langmuir equation can accurately describe the adsorption equilibrium relationship of BSA to the COL/BC microspheres. The pseudo-second-order model can more accurately explain and predict the membrane diffusion kinetics of BSA than both pseudo-primary-order and Kannan-Sundaram intragranular diffusion models. The adsorption rate was affected by both membrane and intragranular diffusions. The drug release behavior indicated that the microsphere-loaded BSA was primarily adsorbed at the inner wall of the pore, and exhibited the characteristics of a scaffold-based matrix meanwhile. The drug release kinetics can be accurately described by the first-order release model. The present study elucidated the mechanism of drug adsorption and release of COL/BC porous microspheres and provided a theoretical basis for its application in controlled release technology.

Mesenchymal stem cells-curcumin loaded chitosan nanoparticles hybrid vectors for tumor-tropic therapy

The combination of controlled release technology and targeted drug delivery has become a promising strategy for cancer therapy. In this study, cell-nanoparticle hybrid vector was constructed using mesenchymal stem cells as the targeting cellular carrier and biotinylated chitosan polymer nanoparticles as the drug depot. Drug-loaded nanoparticles (hydrodynamic size =377.0 ± 14.6 nm and zeta potential = 9.6 ± 1.9 mV) were prepared by encapsulating hydrophobic model drug curcumin into biotinylated chitosan polymer. The biotin-modified nanoparticles were anchored on biotinylated mesenchymal stem cells surface by biotin-avidin binding, achieving an upload of 54.73 ± 3.95 pg/cell. The anchorage of nanoparticles on mesenchymal stem cells had no effect on their viability and homing property. Biotin-avidin binding lasted over 48 h, which could be sufficient for cell-directed tumor-tropic delivery. The in vitro and in vivo anti-tumor results advocate that cell-nanoparticle hybrid vector could prove beneficial in pulmonary melanoma metastasis therapy.

Biochemical effects of banding limit the benefits of nitrification inhibition and controlled-release technology in the fertosphere of high N-input systems

Enhanced efficiency fertilisers (EEFs) may have an important role in improving nitrogen (N) use efficiency in agricultural systems. The performance of EEFs when applied by broadcasting and incorporation is well documented; however, little information is available for sub-surface banded N-fertiliser. This study aimed to determine the effectiveness of EEFs within the fertosphere in several soils. This was determined by: (i) establishing the key chemical effects and N-transformation activity within a urea band, and (ii) contrasting these findings with nitrification inhibitor (NI)-coated urea and a controlled-release polymer-coated urea (PCU). A 112-day incubation experiment was conducted with the EEFs band-applied in three contrasting soils with a history of sugarcane production. In standard urea and NI-urea treated soils, the pH within the fertosphere significantly increased to a maximum of ~pH 9.2–9.3. Alkaline conditions and high ammonium concentrations promoted elevated aqueous ammonia concentrations, resulting in complete nitrification inhibition. The PCU granules released ~40% of total urea content within 14 days, followed by subsequent release at significantly lower rates. The initial rapid urea release was attributed to damaged polymer coats, while close proximity of neighbouring granules within the band may have contributed to the subsequent slower release phase through reduced concentration gradients and restricted diffusion from granules. Variation between soils suggests that soil properties such as clay content and pH buffer capacity may influence urea hydrolysis, but not nitrification. These results suggest that both NI and controlled-release technology may not have the expected impacts on N transformations and availability when applied in a concentrated band.

Taste and dissolution of theophylline extended-release dry syrups

Objectives In this study, we examined the taste and dissolution of theophylline extended-release dry syrups using one branded and six generic formulations. Methods Healthy volunteers underwent sensory testing to assess the syrup taste. Drug dissolution was examined using in vitro dissolution tests. Results and discussion: Syrup taste, including sweetness, bitterness, and aftertaste, was different between formulations. These differences can likely be attributed to the presence of different pharmaceutical additives between formulations. Our results indicated that syrup aftertaste was dependent on the level of sweetness and bitterness. In addition, dissolution behaviors were different between formulations, suggesting bio-inequivalence between formulations. These differences likely reflect the use of different controlled-release technologies between formulations. Conclusions This study provides useful information for selecting branded or generic theophylline extended-release dry syrups for individualized treatments.

Formulation and Controlled Release behavior of Urea Fertilizer from biodegradable superabsorbent composite

Controlled release technology is one of the most efficient techniques to reduce environmental hazards accompanied with fertilizers and herbicides. In the present work, new formulations for controlled release of urea fertilizers were prepared based on biodegradable polymers and agricultural waste. The release behavior of urea fertilizer from the superabsorbent composite was estimated using UV/Vis spectrophotometer. The effect of the pH of the soil on the release rate was also investigated.

Controlled release technology for anti-angiogenesis treatment of posterior eye diseases: Current status and challenges.

Antiangiogenic therapeutics, such as corticosteroids, VEGF targeting antibodies and aptamers have been demonstrated effective in controlling retinal and choroidal neovascularization related vision loss. However, to manage the chronic conditions, it requires long term and frequent intravitreal injections of these drugs, resulting in poor patient compliance and suboptimal treatment. In addition, emerging drugs such as tyrosine kinase inhibitors and siRNAs received much expectations, but the late stage clinical trials encountered various obstacles. Controlled release technology could improve the existing treatment regimen by extending therapeutic duration, reducing risks and burdens caused by frequent injections, and enabling new drugs to overcome the hurdles of translation. Here, we give qualitative and quantitative discussions about the principle mechanisms of polymeric reservoir, polymeric matrix and hydrogel systems. We also reveal the design rationales of the existing drug delivery and release systems in preclinical and clinical stages. Lastly, the animal models of ocular angiogenesis diseases are critically reviewed, which could help to facilitate the translation of controlled release technologies from bench to bedside.

Thermal and morphological characterization of highly porous nanocomposites for possible application in potassium controlled release

The use of fertilizer and water availability are essential factors limiting the agricultural production. The controlled release technology is very promising because it allows the maintenance of fertilizer concentrations within an ideal range avoiding inefficiency and toxicity problems, minimizing the environmental impacts and improving their efficiency. In this context, the nanostructured hydrogels appear as a possible carrier vehicle for these controlled release systems due to their inherent properties, such as biodegradability, low toxicity, and cost, rapid absorption and desorption controlled capacity of water and solutes. In this work, we performed the synthesis of nanostructured hydrogels based on poly(methacrylic acid) (PMAA)/Cloisite-Na+ via free radical polymerization. SEM images indicated a similarity in the basic structure of all nanocomposites. The porous diameter of the hydrogels increased with increasing of nanoclay content. EDS analysis showed the ions belonging to nanoclay present in the nanocomposites, confirming the formation of true nanocomposites. TG–DTG and DSC techniques confirmed an improvement in the thermal stability of nanocomposites caused by the addition of nanoclay. For instance, the degradation initial temperature of the hydrogel was increased from 198.5 to 203.5 °C, and inversely, the degradation rate of the 2° thermal event was decreased from 0.694 to 0.472% min °C−1, when the nanoclay was increased from 0 to 20 mass/%. Moreover, the controlled release investigation showed an improvement in the release time and quantity of the fertilizer released with nanoclay content. This result is very required for this specific application.

Development of Antibody-Drug Conjugates Using DDS and Molecular Imaging.

Antibody-drug conjugate (ADC), as a next generation of antibody therapeutics, is a combination of an antibody and a drug connected via a specialized linker. ADC has four action steps: systemic circulation, the enhanced permeability and retention (EPR) effect, penetration within the tumor tissue, and action on cells, such as through drug delivery system (DDS) drugs. An antibody with a size of about 10 nm has the same capacity for passive targeting as some DDS carriers, depending on the EPR effect. In addition, some antibodies are capable of active targeting. A linker is stable in the bloodstream but should release drugs efficiently in the tumor cells or their microenvironment. Thus, the linker technology is actually a typical controlled release technology in DDS. Here, we focused on molecular imaging. Fluorescent and positron emission tomography (PET) imaging is useful for the visualization and evaluation of antibody delivery in terms of passive and active targeting in the systemic circulation and in tumors. To evaluate the controlled release of the ADC in the targeted area, a mass spectrometry imaging (MSI) with a mass microscope, to visualize the drug released from ADC, was used. As a result, we succeeded in confirming the significant anti-tumor activity of anti-fibrin, or anti-tissue factor-ADC, in preclinical settings by using DDS and molecular imaging.