The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant in vitro antitumor effect against multiple myeloma cells was demonstrated. The therapeutic properties of the nanoplexes were evaluated in vivo against human multiple myeloma xenografts in NOD-SCID mice. The systemic injection of miR-34a mimic-loaded nanoparticles significantly inhibited tumor growth and translated into improved survival of the laboratory mice. RT-PCR analysis carried out on retrieved tumors demonstrated the presence of a high concentration of miR-34a mimics. The integrity of the nanoplexes remained intact and no organ toxicity was observed in treated animals.

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Currently, six liposomal chemotherapeutics have received clinical approval and many more are in clinical trials or undergoing preclinical evaluation. Liposomes exhibit low toxicity and improve the biopharmaceutical features and therapeutic index of drugs, thereby increasing efficacy and reducing side effects. In this review we discuss the advantages of using liposomes for the delivery of chemotherapeutics. Gemcitabine and paclitaxel have been chosen as examples to illustrate how the performance of a metabolically unstable or poorly water-soluble drug can be greatly improved by liposomal incorporation. We look at the beneficial effects of liposomes in a variety of solid and blood-borne tumors, including thyroid cancer, pancreatic cancer, breast cancer and multiple myeloma.

No abstract

The use of cationic polymers, especially polyethylenimine and chitosan, for the in vivo delivery of doubled-stranded RNAs is discussed in this review.