Certainly completion of the CALAA-01 phase I clinical trial, including establishment of a maximum tolerated dose (MTD) and recommended dose level for subsequent trials, is a near-term priority. Thorough evaluation of all of the safety and preliminary efficacy indications from this study will greatly inform the design of a phase II investigation of CALAA-01. Beyond CALAA-01, investigation
of additional therapeutic candidates Inhibitors,research,lifescience,medical employing the RONDEL system, such as those targeting hypoxia-inducible factor-2α (HIF-2α), has been undertaken. The relatively fast clearance of these nanoparticles that has been observed, as has been described above, suggests that strategies to prolong circulation in an effort to enhance tumor accumulation may warrant investigation. The transient elevations in some cytokine Inhibitors,research,lifescience,medical levels seen in interim CALAA-01 clinical data imply that exploration of chemical modifications to the siRNA payload may yield nucleic acids that enhance the nanoparticles therapeutic index. With encouraging interim clinical data in hand, avenues for continued development and improvement of nanoparticles identified, and the emergence of alternative siRNA-containing
nanoparticles in the clinic from which all in this field Inhibitors,research,lifescience,medical will learn, the future for siRNA-containing nanoparticles based on cyclodextrin-containing polycations appears
bright. 9. Conclusions CDP-based nanoparticles have made the transition from the laboratory to the Inhibitors,research,lifescience,medical clinic within the last several years. Two technology platforms have been developed, Cyclosert for small molecule delivery and RONDEL for nucleic acid delivery. Both programs have Inhibitors,research,lifescience,medical produced a clinical candidate for oncology, CRLX101 (formerly IT-101), a camptothecin analog, and CALAA-01, an siRNA therapeutic targeting RRM2. While clinical development is still in the early phases, proof of concept was achieved for both technologies. Clinical development is ongoing and it will be interesting to see what patient benefits these innovative drugs can provide.
The (-)-p-Bromotetramisole Oxalate design and development of simple systems with the aim of delivery and controlled release of hydrophilic drugs administered through oral route are still a challenge. Compared to classical dosage forms, the goals for the development of such systems include maintaining of blood levels for the drug in a therapeutic window for a desired period. Such controlled drug-delivery systems present considerable advantage over conventional dosage forms, but they PR-957 molecular weight involve carrying out specific and complex technologies [1–12]. The most widespread systems giving modified releases are hydrophilic matrix carriers or hydrophilic coating matrix (e.g., on tablets).