The in situ hydrogel drug delivery system is a hot research topic in recent years. Combining both properties of hydrogel and solution, in situ hydrogels can provide many advantages for drug delivery application, including easy application, high local drug concentration, prolonged drug retention time, reduced drug dose in vivo, good biocompatibility and improved patient compliance, thus has potential in tumor treatment. In this paper, the related literature reports in recent years were reviewed to summarize and discuss the research progress and development prospects in the application of in situ hydrogels in tumor treatment.
Large bone defects resulting from trauma, infection and tumors are usually difficult for the body’s repair mechanisms to heal spontaneously. Generally, various types of bones and orthopedic implants are adopted to enhance bone repair and regeneration in the clinic. Due to the limitations of traditional treatments, bone defect repair is still a compelling challenge for orthopedic surgeons. In recent years, bone tissue engineering has become a potential option for bone repair and regeneration. Amidst the various scaffolds for bone tissue engineering applications, hydrogels are considered a new type of non-toxic, non-irritating and biocompatible materials, which are widely used in the biomedicine field currently. Some studies have demonstrated that hydrogels can provide a three-dimensional network structure similar to a natural extracellular matrix for tissue regeneration and can be used to transport cells, biofactors, nutrients and drugs. Therefore, hydrogels may have the potential to be multifunctional sustained-release drug carriers in the treatment of bone defects. The recent applications of different types of hydrogels in bone defect repair were briefly reviewed in this paper.
As the primary site for the biotransformation of drugs, the liver is the most focused on organ type in pharmaceutical research. However, despite being widely used in pharmaceutical research, animal models have inherent species differences, while two-dimensional (2D) liver cell monocultures or co-cultures and three-dimensional (3D) liver cell monoculture in vitro liver models do not sufficiently represent the complexity of the human liver’s structure and function, making the evaluation results from these tools less reliable. Therefore, there is a pressing need to develop more representative in vitro liver models for pharmaceutical research. Fortunately, an exciting new development in recent years has been the emergence of 3D liver cell co-culture models. These models hold great promise as in vitro pharmaceutical research tools, because they can reproduce liver structure and function more practically. This review begins by explaining the structure and main cell composition of the liver, before introducing the potential advantages of 3D cell co-culture liver models for pharmaceutical research. We also discuss the main sources of hepatocytes and the 3D cell co-culture methods used in constructing these models. In addition, we explore the applications of 3D cell co-culture liver models with different functional states and suggest prospects for their further development.
1 September 2019 in International Journal of Nanomedicine
Objective: This study aimed to investigate the interaction between the ion-complementary self-assembling peptide RADA16-I and the hydrophobic drug mangiferin (MA), and the potential of the self-assembling peptide to be exploited as a drug carrier of MA. Methods: The RADA16-I–MA suspension was prepared by magnetic stirring, followed by fluorescence spectrophotometry, particle size determination, rheological properties analysis, and in vitro release assay to characterize the interaction between RADA16-I and MA. Then, the effects of in situ MA-loaded hydrogel on the proliferation of KYSE 30 and DLD-1 tumor cells and the toxic effect of the hydrogel on 293T renal epithelial cells were studied by the Cell Counting Kit 8 method. Results: The RADA16-I–MA suspension was formed in water under magnetic stirring; the in situ hydrogel was formed when the suspension was added to PBS. The particle size in the RADA16-I–MA suspension was around 300–600 nm with an average size of 492 nm. Within 24 h, the cumulative release of MA from the RADA16-I–MA hydrogel was about 80%. The release rate of MA from the hydrogel was dependent on the concentration of RADA16-I and the release can be fitted with a first-order kinetic equation. The results suggested that the self-assembling peptide can stabilize MA in water to form a relatively stable suspension; the results also indicated that controlled release of MA from the RADA16-I–MA in situ hydrogel formed from the RADA16-I–MA suspension can be achieved by adjusting the concentration of the peptide in suspension. The cell viability studies showed that the RADA16-I–MA in situ hydrogel not only can maintain or enhance the intrinsic proliferation inhibition effects of MA on tumor cells, but also can reduce the toxicity of MA to normal cells. Conclusion: The self-assembling peptide RADA16-I can be a potential candidate for constructing a delivery system of the hydrophobic drug MA.
Lung cancer is a major cause of cancer-related deaths worldwide. Stimulus-sensitive hydrogels, which can be formed by responding to stimuli in the cancer microenvironment, have been widely studied as controlled-release carriers for hydrophobic anticancer drugs. In this study, self-assembling peptide RADA16-I was used to encapsulate the hydrophobic drug emodin (EM) under magnetic stirring to form a colloidal suspension, and the colloidal suspension (RADA16-I-EM) was introduced into environments with physiological pH/ionic strength to form hydrogels in situ. The results showed that RADA16-I had good cell compatibility and the RADA16-I-EM in situ hydrogels can obviously reduce the toxicity of EM to normal cells. In addition, compared with free EM (in water suspensions without peptide) at equivalent concentrations, RADA16-I-EM in situ hydrogels significantly reduced the survival fraction of LLC lung cancer cells, while increased the uptake of EM by the cells, and it also induced apoptosis and cell cycle arrest in the G2/M phase more significantly and reduced the migration, invasion, and clone abilities of the cells in vitro. The RADA16-I-EM in situ hydrogels also showed better cancer growth inhibition effects in cancer models (mice bearing LLC cells xenograft cancer), which induced cell apoptosis in the cancer tissue and reduced the toxic side effects of EM on normal tissues and organs in vivo compared with the free EM. It was revealed that RADA16-I can be exploited as a promising carrier for hydrophobic anticancer drugs and has the potential to improve the administration of anticancer drugs to treat cancer effectively with enhanced chemotherapy.
1 January 2022 in Risk Management and Healthcare Policy
Objective: To investigate the current status of knowledge and behavior about rational drug use in college students in different colleges and universities in a city in southwest China, providing reference for students’ education of rational drug use in colleges and universities. Methods: A questionnaire survey on knowledge and behavior in rational drug use was carried out on the students recruited by occasional sampling method in 6 colleges and universities in Zunyi, China. Statistical analyses on demographic information and answers to questionnaire questions were carried out with SPSS 18.0. Results: A total of 865 valid questionnaires were recovered from 923 questionnaires sent out. Some knowledge and behaviors of the students on drug use were irrational. There was statistically significant difference in some specific questions of the knowledge in rational drug use between medical and non-medical students (P< 0.05); the average score of rational drug use behavior of medical students was lower than that of non-medical students (P< 0.05); the average score of the rational drug use behavior of female students was lower than that of male (P< 0.05); the students’ major types had significantly different influence on their behavior in rational drug use (P< 0.05). The school-carried pharmacy education can effectively improve students’ rational medication; the majority of college students believed that it is necessary to popularize the knowledge of rational drug use on campus; and students’ favorite way to acquire knowledge about rational drug use was to attend related lectures or elective courses. Conclusion: The knowledge and behavior of rational drug use among college students need to be improved. Professional medical education may exert a positive impact on rational drug use among college students. Thus, it is necessary to popularize the knowledge of rational drug use among college students, especially in non-medical colleges and universities.