Nanotherapeutics for Nose-to-Brain Drug Delivery: An Approach to Bypass the Blood Brain Barrier

Treatment of neurodegenerative diseases or other central nervous system (CNS) disorders has always been a significant challenge. The nature of the blood-brain barrier (BBB) limits the penetration of therapeutic molecules to the brain after oral or parenteral administration, which, in combination with hepatic metabolism and drug elimination and inactivation during its journey in the systemic circulation, decreases the efficacy of the treatment, requires high drug doses and often induces adverse side effects. Nose-to-brain drug delivery allows the direct transport of therapeutic molecules by bypassing the BBB and increases drug concentration in the brain. The present review describes mechanisms of nose-to-brain drug delivery and discusses recent advances in this area with especial emphasis on nanotechnology-based approaches

Nanotechnology approaches for inhalation treatment of lung diseases

AbstractLocal administration of therapeutics by inhalation for treatment of lung diseases has the ability to deliver drugs, nucleic acids and peptides specifically to the site of their action and therefore enhance the efficacy of the treatment, limit the penetration of nebulized therapeutic agent(s) into the bloodstream and consequently decrease adverse systemic side effects of the treatment. Nanotechnology allows for a further enhancement of the treatment efficiency. The present review analyzes modern therapeutic approaches of inhaled nanoscale-based pharmaceutics for the detection and treatment of various lung diseases

Development of Liposomal Vesicles for Osimertinib Delivery to EGFR Mutation—Positive Lung Cancer Cells

Osimertinib (OSI, AZD9291), is a third-generation, irreversible tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. OSI has been approved as a first-line treatment of EGFR-mutant lung cancer and for metastatic EGFR T790M-mutant non-small cell lung cancer. Liposome-based delivery of OSI can provide a new formulation of the drug that can be administered via alternative delivery routes (intravenous, inhalation). In this manuscript, we report for the first time development and characterization of liposomal OSI formulations with diameters of ca. 115 nm. Vesicles were composed of phosphatidylcholines with various saturation and carbon chain lengths, cholesterol and pegylated phosphoethanolamine. Liposomes were loaded with OSI passively, resulting in a drug being dissolved in the phospholipid matrix or actively via remote-loading leading to the formation of OSI precipitate in the liposomal core. Remotely loaded liposomes were characterized by nearly 100% entrapment efficacy and represent a depot of OSI. Passively-loaded vesicles released OSI following the Peppas-Sahlin model, in a mechanism combining drug diffusion and liposome relaxation. OSI-loaded liposomes composed of l-α-phosphatidylcholine (egg-PC) demonstrated a higher toxicity in non-small lung cancer cells with EGFR T790M resistance mutation (H-1975) when compared with free OSI. Developed OSI formulations did not show antiproliferative activity in vitro in healthy lung epithelial cells (MRC-5) without the EGFR mutation

Nanotechnology-Based RNA Vaccines: Fundamentals, Advantages and Challenges

Over the past decades, many drugs based on the use of nanotechnology and nucleic acids have been developed. However, until recently, most of them remained at the stage of pre-clinical development and testing and did not find their way to the clinic. In our opinion, the main reason for this situation lies in the enormous complexity of the development and industrial production of such formulations leading to their high cost. The development of nanotechnology-based drugs requires the participation of scientists from many and completely different specialties including Pharmaceutical Sciences, Medicine, Engineering, Drug Delivery, Chemistry, Molecular Biology, Physiology and so on. Nevertheless, emergence of coronavirus and new vaccines based on nanotechnology has shown the high efficiency of this approach. Effective development of vaccines based on the use of nucleic acids and nanomedicine requires an understanding of a wide range of principles including mechanisms of immune responses, nucleic acid functions, nanotechnology and vaccinations. In this regard, the purpose of the current review is to recall the basic principles of the work of the immune system, vaccination, nanotechnology and drug delivery in terms of the development and production of vaccines based on both nanotechnology and the use of nucleic acids

Nanotechnology approaches for personalized treatment of multidrug resistant cancers

AbstractThe efficacy of chemotherapy is substantially limited by the resistance of cancer cells to anticancer drugs that fluctuates significantly in different patients. Under identical chemotherapeutic protocols, some patients may receive relatively ineffective doses of anticancer agents while other individuals obtain excessive amounts of drugs that induce severe adverse side effects on healthy tissues. The current review is focused on an individualized selection of drugs and targets to suppress multidrug resistance. Such selection is based on the molecular characteristics of a tumor from an individual patient that can potentially improve the treatment outcome and bring us closer to an era of personalized medicine