ABSTRACT
Osimertinib is an irreversible third representative epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the treatment of non-small cell lung cancer (NSCLC) with T790M resistance and classical EGFR mutations. However, the therapeutic effectiveness of osimertinib is limited by acquired drug-resistance, poor water solubility and low tumor accumulation rates. Nanodrug delivery systems can increase the solubility and stability of drugs, prolong the blood circulation time of drugs, improve the uptake rate of cells, promote drug accumulation in tumor tissues, and improve drug resistance. Thus, they are effective in overcoming the limitations of traditional targeted drugs. In this study, we reviewed the mechanism of action of the third-generation EGFR-TKI osimertinib, focused on research advances in osimertinib nanodrug delivery systems against NSCLC, and explored the challenges and future development direction in this field.
ABSTRACT
Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.
Subject(s)
Animals , Drugs, Chinese Herbal/chemistry , Plants, Medicinal , Antioxidants , Anti-Inflammatory Agents , Drug CarriersABSTRACT
Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.
Subject(s)
Nanomedicine , Nucleosides/chemistry , Nucleotides , Nanoparticles/chemistry , Drug Delivery Systems , Drug CarriersABSTRACT
Messenger RNA (mRNA) has shown tremendous potential in disease prevention and therapy. The clinical application requires mRNA with enhanced stability and high translation efficiency, ensuring it not to be degraded by nucleases and targeting to specific tissues and cells. mRNA immunogenicity can be reduced by nucleotide modification, and translation efficiency can be enhanced by codon optimization. The 5´ capping structure and 3´ poly A increase mRNA stability, and the addition of 5' and 3' non-translational regions regulate mRNA translation initiation and protein production. Nanoparticle delivery system protects mRNA from degradation by ubiquitous nucleases, enhances mRNA concentration in circulation and assists it cytoplasmic entrance for the purpose of treatment and prevention. Here, we review the recent advances of mRNA technology, discuss the methods and principles to enhance mRNA stability and translation efficiency; summarize the requirements involved in designing mRNA delivery systems with the potential for industrial translation and biomedical application. Furthermore, we provide insights into future directions of mRNA therapeutics to meet the needs for personalized precision medicine.
Subject(s)
RNA, Messenger/genetics , Cytoplasm , Nanoparticles , Precision MedicineABSTRACT
@#Dental caries are the most common and widespread biofilm-dependent oral disease. Nanotechnology promises to be a useful strategy for dental caries management by combating caries-related bacteria, decreasing biofilm accumulation, inhibiting demineralization and enhancing remineralization. Many potential applications of nanotechnology in the development of anticaries materials have recently been reported, especially for anticaries adhesive nanomaterials and anticaries nanofilled composite resins. This review summarizes the current progress in the application of functional nanoparticles in the following products: antibacterial nanomaterials, remineralizing nanomaterials and nanodrug delivery systems.
ABSTRACT
Phospholipids are the major components of the biomembrane. Combining the phospholipids and the drugs to form drug-phospholipid complex can improve the solubility, stability and bioavailability of the drugs. On this basis, the nanodrug delivery system, which is constructed with the drug- phospholipid complex as an intermediate carrier, has become a research hot spot in the field of pharmaceutics. This kind of nanodrug delivery system can not only improve the solubility, stability and bioavailability of drugs, but also carry out the targeted drug delivery, decrease the drug dose and reduce the side effects, thereby it is very promising. In this review, we describe the structural composition, characteristics, forming mechanism of the drug-phospholipid complex and the research progresses in a variety of nanodrug delivery systems based on drug-phospholipid complex.
ABSTRACT
Dental caries and periodontal diseases are common chronic infectious diseases that cause serious damage to oral health. Bacteria is the primary factor leading to such conditions. As a dental plaque control method, chemotherapeutic agents face serious challenges in dental care because of the specific physiological and anatomical characteristics of the oral cavity. Nanodrug delivery system is a series of new drug delivery systems at nanoscale, and it can target cells, promote sustainedrelease effects, and enhance biodegradation. This review focuses on research progress on nanodrug delivery systems for prevention and control of dental caries and periodontal diseases.
Subject(s)
Humans , Dental Care , Dental Caries , Dental Plaque , Drug Delivery Systems , Periodontal DiseasesABSTRACT
Phospholipids are the major components of the biomembrane. Combining the phospholipids and the drugs to form drug-phospholipid complex can improve the solubility,stability and bioavailability of the drugs. On this basis,the nanodrug delivery system,which is constructed with the drug-phospholipid complex as an intermediate carrier,has become a research hot spot in the field of pharmaceutics. This kind of nanodrug delivery system can not only improve the solubility,stability and bioavailability of drugs,but also carry out the targeted drug delivery,decrease the drug dose and reduce the side effects,thereby it is very promising. In this review,we describe the structural composition,characteristics,forming mechanism of the drug-phospholipid complex and the research progresses in a variety of nanodrug delivery systems based on drug-phospholipid complex.
ABSTRACT
OBJECTIVE: Chemotherapy is the primary treatment in addition to surgery and radiotherapy in cancer therapy, and drug resistance of tumor cells remains a major obstacle to successful cancer chemotherapy. In present study, we aim to develop a novel drug delivery system, ie, doxorubicin (DOX) conjugated poly (amido amine) (PAMAM) dendrimers was further decorated by hyaluronic acid (HA) (DOX-PAMAM-HA) to circumvent drug resistance in cancer cells. METHODS: Nuclear magnetic resonance (NMR) was performed to confirm the synthesis of the DOX-PAMAM-HA, its average size was analyzed by a dynamic light-scattering detector, and its morphological examination was performed by transmission electron microscope (TEM). To study the ability of DOXPAMAM-HA in overcome multi-drug resistance, the multi-drug resistant breast cancer cells (MCF-7/ADR cells) was used as model cell, and the confocal microscopy was utilized to observe the drug intracellular distribution, moreover, the hematoxylin-eosin staining (HE) studies were employed to evaluate the tissue staining and toxicity. RESULTS: The drug delivery system DOX-PAMAM-HA was successfully synthesized, which is spherical particles with a average particle size of 323 nm. The uptake in MCF-7/ADR cells for DOXPAMAM-HA is higher than that of DOX solution, and DOX-PAMAM-HA maybe distribute mainly in the lysosome of the cells, which could increase the accumulation of DOX in its action target (nucleus). In contrast, DOX solution was mainly diffused in the cytoplasm of the tumor cells. Furthermore, less toxicity in heart and spleen induced by DOX-PAMAM-HA in comparing to that of DOX solution after intravenous administration for 3 weeks. CONCLUSION: DOX-PAMAM-HA is a prospect future nanodrug delivery system in overcoming drug-resistance of tumor cells.