Critical Reviews in Therapeutic Drug Carrier Systems最新文献

Brain tumors pose a serious burden to health care because the cancers are usually incurable, despite advancements in treatment strategies including surgery, radiotherapy, and chemotherapy. Most studies report that specific drugs are effective in vitro, but many lose their therapeutic value in clinical settings. Maintaining therapeutic drug concentrations as an agent reaches a cancer target is the efficacy prerequisite for any form of treatment. However, in the case of brain tumors, the blood-brain barrier (BBB) acts to physically and physiologically block the drug, which complicates treatment options. In addition, strategies are limited by a number of factors such as difficulties that are associated with targeting tumor cells. The therapeutic potential of targeted drug delivery as an alternative to current strategies is gaining significant ground, with many studies highlighting its efficacy and compatibility in overcoming the BBB before reaching its final target in brain. In this review, we briefly describe basic physiology associated with the BBB and how modern science is taking advantage of physiological processes to deliver anticancer agents to brain. We also summarize different modes of drug delivery and highlight how nanoparticles as drug-delivery vehicles are used for drug transport in brain tumors as well as different types of surface modification that are used to increase target potential.

Exosomes are endogenous extracellular vesicles (30-100 nm) composed with membrane lipid bilayer which carry vesicular proteins, enzymes, mRNA, miRNA and nucleic acids. They act as messengers for intra- and inter-cellular communication. In addition to their physiological roles, exosomes have the potential to encapsulate and deliver small chemotherapeutic drugs and biological molecules such as proteins and nucleic acid-based drugs to the recipient tissue or organs. Due to their biological properties, exosomes have better organotropism, homing capacity, cellular uptake and cargo release ability than other synthetic nano-drug carriers such as liposomes, micelles and nanogels. The secretion of tumor-derived exosomes is increased in the hypoxic and acidic tumor microenvironment, which can be used as a target for nontoxic and nonimmunogenic drug delivery vehicles for various cancers. Moreover, exosomes have the potential to carry both hydrophilic and hydrophobic chemotherapeutic drugs, bypass RES effect and bypass BBB. Exosomes can be isolated from other types of EVs and cell debris based on their size, density and specific surface proteins through ultracentrifugation, density gradient separation, precipitation, immunoaffinity interaction and gel filtration. Drugs can be loaded into exosomes at the biogenesis stage or with the isolated exosomes by incubation, electroporation, extrusion or sonication methods. Finally, exosomal cargo vehicles can be characterized by ultrastructural microscopic analysis. In this review we intend to summarize the inception, structure and function of the exosomes, role of exosomes in immunological regulation and cancer, methods of isolation and characterization of exosomes and products under clinical trials. This review will provide an inclusive insight of exosomes in drug delivery.

Oral cancer is the 11th most common cancer in the world with a high morbidity rate. Various conventional therapies have been used for the treatment of oral cancer such as surgery, radiotherapy, and chemotherapy used either alone or in combination but these have many limitations, making them unsuitable for treating oral cancer. Nanotechnology has been emerged out as an innovative tool in the field of oral cancer which has proved to provide effective results overcoming the limitations of conventional drug therapies. This system involves a nanoparticle drug delivery system based on a targeted therapy in which therapeutic drugs or agents act on the targeted cells without affecting normal healthy cells. Literature has shown that several nanoparticles, organic and inorganic nanoparticles, have been used as the drug delivery system in different types of oral cancers such as oral squamous cell carcinoma, cancer of the tongue, head, and neck cancers. Drugs like cisplatin, 5-fluorouracil, methotrexate, doxorubicin, etc., when coated with nano-polymers have shown better results compared with conventional drugs in oral cancer. Other nanoparticles such as liposomes, hydrogels, nanodiamonds, carbon rods, etc. have also been used with minimal side effects. This paper aims to review and discuss various nanotechnology systems in the field of oral cancer and to evaluate the efficacy of these systems in treating oral cancer compared with conventional drug delivery methods.

Viral infections such as AIDS, hepatitis, herpes keratitis, and herpes labialis became resistant to drugs and it is difficult to design vaccine. In current era drug-resistant viruses are now treated by nanoparticles (NPs) and this field is known as nanobiotechnology that relates nanoscience with the biological system. NPs due to their antiviral activity are used in the treatment of viral diseases. The advantages of using the NP is its specific target action and increase the efficiency of treatment with minimum side effects. Liposomes, quantum dots, polymeric NPs, solid lipid NPs, silver NPs, gold NPs, and magnetic NPs are used to treat viral infections. NP-based therapeutics have completely replaced the usage of drugs and vaccines for viral diseases treatment. Nano vaccines have been investigated for the delivery of drugs; biomaterials-based NPs are in development to be formulated into nano vaccines. But there are limitations in the manufacturing and stabilization of NPs in the body. This review focuses on the antiviral activity of several NPs, its uptake by different viruses for viral disease treatment, nano vaccines, and the limitation of the NPs as nanotherapeutics.

Applications of nanoceria in the biomedical field are quite promising, as previous data has shown potential use of nanoceria as therapeutics via radical scavenging and oxidative stress mitigating properties. But, still, there are contradicting reports regarding nanoceria activity, mode of action, and in vitro toxicity in the cell. There are different nanoceria synthesis methods and Ligands for functionalization and loading of nanoceria into drugs for targeted drug delivery. Redox chemistry of nanoceria exerts their anticancer properties through apoptosis and oxidative stress as it can switch between Ce3+ and Ce4+ and act as free radical scavengers. For breast cancer treatment, cerium oxide nanoparticles (CeONPs) can act as protectant for healthy cells against on-going radiotherapy. Similarly, CeONPs were used to make pancreatic cancer cells more sensitive to radiation damage setting them on the apoptotic pathway. Herein, the study reflects the use of nanoceria as a drug delivery system in chemotherapy due to its efficiency in acidic pH and oxidase activity in the microenvironment. A controlled drug delivery system was adapted using a nano-complexes of AMD-GCCNP-DOX, which were then employed against the retinoblastoma cells from the human eye to target the overexpressing chemokine receptor 4 (CXCR4). In radiotherapy, nanoceria acts as radioprotectants due to their free radical scavenging property and inhibit the proliferation and migration of gastric cancer. This paper summarizes the synthesis methods and application of nanoceria in cancer.

In recent years, allergies are on the rise. The growth of allergies cases has changed the immune system's response to new pathogens. The therapy used to treat these diseases is based on allergen avoidance, pharmacotherapy and allergen-specific immunotherapy. The last one has received a lot of interest in the research field, due to the possibility of leading the patient to a cure. In this sense, new allergen immunotherapy need to be developed or improved to increase safety and efficiency. This review aims to evaluate patents published, from 2015 to July 2020, that have developed allergic immunotherapy treatment and administration routes, as well as new alternatives of vehicles, carriers and delivery systems in this context. The advance of new patents has been mostly seen in China and United States. The oral route is the most used in the development of new allergy treatments. However, due to the challenges that still exist in allergy therapy, association with other pathways is interesting to amplify the possibilities and alternatives of treatment. Thus, other routes of administration for allergen-specific immunotherapy such as topical, sublingual and intranasal have been explored in the research and industrial fields. Nevertheless, it has been observed that few studies are using these alternative administration routes, probably due to the higher cost and lack of investments. The delivery systems are also other tools that can be more explored in the allergen immunotherapy formulations. The effectiveness, safety and acceptance of this therapy depends on the development of new formulations and routes of administration.

Several ocular drug delivery (ODD) systems, like hydrogels, microparticles, nano-emulsions, micro-emulsions, and liposomes have been researched, which can govern the drug release and sustain therapeutic levels for a delayed period in the eye. While new drugs targeting methods to the eye are possible by various nanoparticles. Presently in the market, there are fewer choices and need for novel nano-ocular delivery systems as well as therapies for prolonged delivery to the anterior and posterior eye segments. The primary objective of this article is to summarize current discoveries and proven activities of different nano- and microsystems in ODD. This article also depicts some regulatory updates along with the patents granted to the inventor for their work on ODD. Overall, a thought of how the different forthcoming of nanotechnologies like nanoparticles and nanomedicine can be used to investigate the frontiers of ODD and treatment can be withdrawn by this article.

Self-emulsifying drug delivery system (SEDDS), a category of lipid-based technology, has gained interest in the recent years for enhancement of solubility and bioavailability of poorly water-soluble drugs. With the progress of research in this field, novel excipients have been developed with enhanced properties. But excipient selection is the key hurdle in the formulation of SEDDS. The objective of this review is to summarize different types of oils, surfactants, co-surfactants which are the key components of liquid SEDDS (L-SEDDS), various carriers utilized in the conversion of L-SEDDS to solid SEDDS (S-SEDDS), their description, properties, grades, and applications in pharmacy. This article provides an overview of solidification techniques to transform L-SEDDS to S-SEDDS which are more stable and have better patience compliance. This review presents numerous literature reports on various excipients used and the discussion on how these excipients affect the final results.

There is emergent need for in vitro models which are physiologically correct, easy to reproduce, and mimic characteristic functionalities of desired tissue, organ, or diseases state for ophthalmic drug screening, as well as disease modeling. To date, a variety of in vitro models have been developed for the applications ranging from 2D cell culture-based monolayers, multilayer, or co-culture models, to 3-dimensional (3D) organoids, 3D printed and organ on chip systems. Each model has its own pros and cons. While simple models are easier to create, and faster to reproduce, they lack recapitulation of the complex framework, functionalities, and properties of tissues or their subunits. Recent advancements in technologies and integration with tissue engineering and involvement of microfluidic systems have offered novel platforms which can better mimic the in vivo microenvironment, thus possessing potential in transformation of ophthalmic drug development. In this review we summarize existing in vitro ocular models while discussing applicability, drawbacks associated with them, and possible future applications.