Measuring Bullet Shell - A New Carbon Quantum Dot Coating System Leads a New Era of Healthy Aquaculture
At present, livestock and poultry infectious diseases in the breeding industry seriously threaten animal and human health, food supply safety and public health safety, and veterinary pharmaceutical companies are faced with three major pain points: difficult to control the dosage, insufficient antibacterial effect, lack of targeting of existing veterinary drug carriers, and small dosage of target organs. The existing veterinary drug dosage forms are mainly divided into non-coated API tablet injections and sustained-release capsule dosage forms with simple coating improvement, which are called coating "0.0" and coating "1.0", respectively. Although targeted nanopolymer material veterinary drug targeted preparations have been marketed by pharmaceutical companies, the targeted coating preparations are developed in-house and sold after the drug, rather than being promoted and circulated by the coating shell itself, which has extremely large technical barriers and high costs.
In view of the shortcomings of the existing drug coating system, the team created a drug-loaded carbon quantum dot system with synergistic antimicrobial, targeted drug delivery, and in vivo detection functions, and improved its one-step hydrothermal preparation method, which reduced the preparation cost of microspheres by 20% and increased the yield by 100%. Targeting to solve the three major pain points, as the only supplier of veterinary drug microsphere carrier itself, create the "2.0" era of veterinary drug coating, break the technical barriers in the market, enter the blue ocean market of veterinary drug coating system, effectively improve the efficacy of microspheres and targeting, reduce costs, and escort healthy breeding.
The original heart originates, and the ambition of the great bird is established
In the summer of 2015, team leader Huang Jiayi witnessed a sudden large-scale death of livestock in a small farm of a relative's family, and the breeding operation suffered heavy losses overnight. After seeing the serious consequences of bacterial infections in poultry, she became more interested in the problem of bacterial infections and delved into the knowledge about bacterial infections.
With the passage of time, the scene of large-scale death of livestock due to bacterial infection is vivid. She has been concerned about the problem of bacterial infections in poultry and livestock for a long time, and she began to read a lot of articles and research in this area, and has a deeper understanding of bacterial infections in poultry and livestock, and gradually noticed the difference between human and veterinary drugs, and she found that coating technology can greatly increase the stability of drugs. However, veterinary drugs lack the technology in this area, and targeted drugs have a poor mechanism of action and are expensive. After learning about the relevant information, Huang Jiayi, the team leader, was determined to provide a solution to this problem. In the end, with a heart of love for agriculture and rejuvenating agriculture, Huang Jiayi chose to apply for China Agricultural University after the college entrance examination and studied veterinary medicine.
Mechanics practice, practice far-reaching
After entering the school in 2021, the school and college have provided many practical opportunities, and the teachers have also explained the problem of bacterial infection diseases in livestock and poultry many times. In the process of continuous study and research, Huang Jiayi became more and more clear and determined about the specific direction of entrepreneurship, and then found two like-minded companions to form a team, and found her mentor, Professor Hao Zhizhi, a distinguished professor of Changjiang Scholars. Under the guidance and support of the teacher, from the initial reading and research of relevant literature to the gradual planning of a series of research and social practice work, they conducted in-depth research on the livestock breeding situation of many typical breeding enterprises and individual farmers, and took the initiative to go deep into the front line of the industry to understand the situation and obtain effective information.
While the practical research continued to advance, the team also contacted the teacher and entered the laboratory in October 2021 to start the research work. In the following months, the team worked together to overcome the difficulties, and finally independently designed the coating "2.0" experimental plan and began to practice the experiment. During the entire research and development period, the technical team of the measuring bullet shell stayed at the school for the winter and summer vacations, which lasted until July 2022. During this time, the team continued to solve various technical challenges, and finally succeeded in developing a new coating technology that can improve the stability of the drug and effectively inhibit bacterial infection. Between February and June 2022, the team also solved the problem of targeting, enabling the development of a new coating technology to more precisely target bacterial infections. In the end, Huang Jiayi, the team leader, wrote a core paper as the first author.
Down-to-earth and fruitful
Through the research and development process of this technological innovation, it can be seen that this innovative technology began with a focus on the problem of bacterial infections and the lack of development of coating technology in the field of veterinary drugs. After finding like-minded peers and receiving guidance and support from Changjiang Scholars, the team defied difficulties and persisted in pursuit, and finally succeeded in developing a new coating technology.
(1) Natural ingredients, safe and non-toxic
For the first time, the team proposed and confirmed that carbon quantum dots can assist other drugs to enhance their antibacterial effects, screened relevant raw material components, and created Fe3+ selective adsorption of carbon quantum dots with citric acid and polylysine as the main components. The core raw materials of the team's products are all biological raw materials and their polymers, which are non-toxic and irritating to the body and can be naturally degraded in the body. The team's experiments showed that the product had no significant cytotoxicity and hemolytic activity. Polymer is a degradable excipient, degraded into water and carbon dioxide in the body, with high safety, combined with natural biopolymers, the drug encapsulated in the nanoscale polymer microsphere body, can effectively reduce the frequency of administration, stabilize the blood concentration and reduce the toxic side effects of the drug itself, thereby increasing the stability of the drug. The drug is continuously released within 24 hours, which has a significant sustained-release effect compared with the existing carrier, and improves the drug utilization rate.
(2) Synergistic antibacterial and enhanced efficacy
For the first time, the team proposed and validated carbon quantum dots that can be synergistically antibacterial. Synergistic antibacterial and enhanced efficacy: multiple bacteria form bacterial communities with polysaccharide adhesion, and the polysaccharide envelope is the bacterial biofilm. The membrane makes the bacteria very resistant, leading to the growth of the disease course, if too many antibiotics are used and the bacterial resistance is enhanced, it is easy to form "superantigens", which becomes a great problem in infection prevention and control. Polylysine has the effect of penetrating biofilm and inhibiting bacteria, and citric acid can be used as a Fe3+ adsorption carrier to destroy the formation process of bacterial biofilm, and the advantages of the two materials can inhibit the growth of bacterial biofilm and bacteria. Experiments show that carbon quantum dots have a good inhibitory effect on drug-resistant bacteria and common pathogens.
(3) Technological innovation and a number of breakthroughs
1. Cost reduction: The one-step hydrothermal production method of carbon quantum dot system is easy to control, simple, economical, energy-saving, and has a high application prospect, but it has high temperature requirements, long process time, and low quantum yield. In view of the cost-sensitive characteristics of veterinary drugs and the physical and chemical properties of citric acid-polylysine and other components, the team innovated the one-step hydrothermal preparation method of carbon quantum dots, optimized the best variables, and used a heating temperature of 130 °C for 6 hours reaction time, covering the four stages of dehydration, polymerization, passivation, and carbonization, and then obtained carbon quantum dot microspheres with characteristic particle size through dialysis and freeze-drying.
2. Enhanced targeting: Our team used the high osmotic long retention effect (EPR effect) of nanomaterials and carbon quantum dots nanomaterials to effectively increase the blood concentration of lesions and reduce systemic toxicity and side effects. Taking lung as an example, the preparation method of our product can obtain a lung targeted carbon quantum dot microsphere with uniform particles, with a lung distribution rate of 66.5% at 1 h and 97.8% at 10 h.
3. Stable sustained release: The team innovated the combination of natural biopolymers to encapsulate the drug in the nano-scale polymer microsphere body, and the microspheres were slowly released at the administration site, which can effectively reduce the frequency of administration, stabilize the blood concentration, reduce the fluctuation of blood drug concentration, and reduce toxic side effects. Laboratory testing can maintain the blood concentration of the lesion for up to 24 hours.
(4) The first in the field and the future is bright
Relying on the leading advantages of A+ discipline science and technology research and development, and the research foundation of the mentor platform for more than ten years, the quantum "bullet shell" technical team has achieved the same universality and promotion value by creating new formulas and optimizing the process flow to achieve the prospects, but the cost is lower, and the carrier synergistic drug has excellent sustained release, targeting and bacteriostatic properties, which is suitable for breeding leaders who are willing to add a little more "small cost" to increase "big benefits". For the first time, nanosystems were applied to veterinary bacterial treatment.
Work together in the same boat and take root in practice
With the breakthrough of technological achievements, the team has widely absorbed talents, formed a multidisciplinary cross-integration situation, realized the integration of veterinary medicine, immunology, statistics and other disciplines, and the entrepreneurial team worked together to overcome the difficulties, gradually moving from immaturity to initial maturity, and also promoted the promotion and pilot of product technology. Since September 2022, relying on the brand advantages of the University of Agricultural Sciences and the resource platform of the university, the Shell Measurement team has carried out pilot practice certification with a number of downstream farms, such as the trial of Shandong Taikoo Zhuang Farm, as well as the recognition and exchange of some enterprises, such as Qingdao Zhongren and Shandong Xinde. In addition, the shell of the bullet has gone deep into the actual situation in the countryside, entered the agriculture, walked into the countryside, approached the farmers, carried out field interviews and local pilots, solved practical problems for many individual farmers, and received a letter of thanks from Chen Liang, an individual farmer.
Entrepreneurial insights
Zhizhi practices the original intention, and sublimates to help the agricultural foundation
In his reply letter to the students of the Science and Technology Academy of China Agricultural University, General Secretary Xi Jinping emphasized that young people should "cultivate love for agriculture and practice the ability to rejuvenate agriculture". The project of starting from agriculture, serving agriculture and innovating in agriculture. As a student of agricultural science, we must always keep in mind the responsibility and mission of revitalizing agriculture and loving agriculture, always pay attention to agricultural development issues, and keep in mind the goal and mission of building a strong agricultural country. The road to entrepreneurship in the agricultural field is bound to be difficult and full of ups and downs, but it is undoubtedly great and valuable. On the road of entrepreneurship, everyone should not forget their original intention and work hard; Every traveler should be rooted in practice. Start a business, we're on your way!