Band 8, Heft 2

Many nanomaterials were developed for the anticipated in vivo theranostic use exploiting their unique characteristics as a multifunctional platform. Nevertheless, only a few nanomaterials are under investigation for human use, most of which have not entered clinical trials yet. Radionanomedicine, a convergent discipline of radiotracer technology and use of nanomaterials in vivo, can facilitate clinical nanomedicine because of its advantages of radionuclide imaging and internal radiation therapy. In this review, we focuse on how radionanomedicine would impact profoundly on clinical translation of nanomaterial theranostics. Up-to-date advances and future challenges are critically reviewed regarding the issues of how to radiolabel and engineer radionanomaterials, in vivo behavior tracing of radionanomaterials and then the desired clinical radiation dosimetry. Radiolabeled extracellular vesicles were further discussed as endogenous nanomaterials radiolabeled for possible clinical use.

Radionanomedicine is the medical field which uses radioisotope labeled nanomaterials for diagnostic, therapeutic or theranostic purposes. An amphiphile- encapsulation method has been developed to hydrophilize nanoparticles and the introduction of multifunctional ligands. A copper-free click chemistry has been applied for introduction of various ligands to the nanoparticles. The combination of the amphiphile-encapsulation method and click chemistry might provide a versatile nano-platform to radionanomedicine, which might contribute to the earlier clinical application of radionanomedicine for theragnosis of various diseases.

Cyclosporine is considered a highly lypophilic compound meaning low bioavailability through oral administration. In this study, cyclosporine was entrapped in a novel aromatic, quaternized derivative of chitosan (i.e. methylated N-(4-N,N-dimethyl aminobenzyl) chitosan) in order to improve solubility and bioavailability. Methylated N-(4,N,N-dimethyl aminobenzyl) chitosan was synthesized by the Schiff base reaction method. Polymeric nanoparticles containing cyclosporine was prepared and the physico-chemical properties of prepared nanoparticles were determined. The nanoparticles were studied morphologically using transmission electron microscopy (TEM). Finally, the release of cyclosporine from nanoparticles was studied in vitro using simulated intestinal fluid adjusted to pH of 6.8. For the preparation of nanoparticles, different formulations were studied and it was found that proper nanoparticles were prepared in equal concentration (1 mg/mL) of polymer and sodium tri-poly phosphate (TPP). The size, zeta potential, PdI, EE% and LE% of the prepared nanoparticles were reported as 173±36 nm, 23.1±4.18 mV, 0.243±0.05, 97.1±4.38% and 3.2±0.21%, respectively. The TEM images of nanoparticles revealed spherical to sub-spherical nanoparticles with no sign of agglomeration. This study suggests that preparations of nanoparticles composed of methylated N-(4,N,N-dimethyl aminobenzyl) chitosan can be a good candidate for improving the oral bioavailability of cyclosporine.

Surface modified self-nanoemulsifying formulations (SNEFs) loaded with gentamicin were formulated using suitable blends of soybean oil, a mixture of Kolliphor ® P188 and Kolliphor ® EL as surfactants, and Transcutol ® HP as co-surfactant, and administered orally to white albino rats for evaluation of anti-pneumococcal activity against Streptococcus pneumoniae . Droplet size and zeta potential measurements showed that SNEFs had mean droplet sizes in the range of 80.7±0.5–210.2±0.0, and were stable with mean zeta potential in the range of –25.2±3.0 to –42.5±1.3 mV. Preliminary screening against S. pneumoniae in vitro revealed that gentamicin-loaded SNEFs had better bacterial inhibition than the standard drug, and at a low minimum inhibitory concentration (MIC) of 2.5 mg/mL. Gentamicin delivered into cerebrospinal fluid of rats from orally administered SNEFs produced a prolonged and enhanced activity against S. pneumoniae at a dose of 7 mg/kg than the standard drug at the same dose. Hence, results from this study showed that the activity of gentamicin against S. pneumoniae was improved by formulation as surface modified SNEFs.