Nanoparticle delivery for central nervous system diseases and its clinical application

In the treatment of central nervous system(CNS)diseases such as glioma,Alzheimer's disease(AD)and Parkinson's disease(PD),drugs are expected to reach specific areas of the brain to achieve the desired effect.Although a growing number of therapeutic targets have been identified in preclinical studies,the ones that can ultimately be used in the clinic are limited.Therefore,the research process and clinical application of drugs for treating CNS diseases are still large challenges.Physiological barriers such as the blood‒brain barrier(BBB)act as selective permeable membranes,allowing only certain molecules to enter the brain;this barrier is the major obstacle restricting the arrival of most drugs to brain lesions.Recently,nanoparticles,including lipid-based,cell-derived biomimetic,polymeric and inorganic nanoparticles,have gained increasing attention because of their ability to cross physiological barriers,and could play an important role as delivery carriers and immunomodulators.Additionally,clinical applications of nanoparticles in CNS diseases are underway.This review focuses on the progress of current research on the use of nanoparticles for the treatment of CNS diseases to provide additional insight into the treatment of CNS diseases.

Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers（NLCs）.The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC.The influence of different parameters on migration times,peak symmetry,efficiency and resolution was studied;these parameters included the pH of the electrophoretic buffer solution and the applied voltage.The piroxicam peak was obtained with a satisfactory resolution.The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9.The optimal voltage was 20 kV and the cartridge temperature was 20 ℃.The corresponding calibration curve was linear over the range of 2.7-5.4 μg/mL of NLC suspension.The reproducibility of migration time and peak area were investigated,and the obtained RSD%values（n = 5） were 0.99 and 2.13.respectively.

Extracellular vesicles:Emerging tools as therapeutic agent carriers

Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient cells in cell-to-cell communication.Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy.EVs can also natively carry or be modified to contain therapeutic agents(e.g.,nucleic acids,proteins,polysaccharides,and small molecules)by physical,chemical,or bioengineering strategies.Due to their excellent biocompatibility and stability,EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction,immunoregulation,or other therapeutic effects,which can be targeted to specific cell types.Herein,we review EV classification,intercellular communication,isolation,and characterization strategies as they apply to EV therapeutics.This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications,using representative examples in the fields of cancer chemotherapeutic drug,cancer vaccine,infectious disease vaccines,regenerative medicine and gene therapy.Finally,we discuss current challenges for EV therapeutics and their future development.

Entrapment and Sustained Release of Hydrophobic Drugs with Different Molecular Weights from PHBHHx-PEG Nanoparticles

Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 （PEG200） end-capped poly （3-hydroxybutyrate-co-3-hydroxyhcxanoate） （PHBHHx-PEG） was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil （5-Fu, Mw=130.1）, TGX221 （Mw=364.4）, and Rapamycin （RAP, Mw=914.2） were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1% and 74.7% after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.