Clinical translational challenges in nanomedicine
- PDF / 445,180 Bytes
- 6 Pages / 585 x 783 pts Page_size
- 59 Downloads / 282 Views
Introduction Research into the use of nanotechnology in medicine cuts across all fields; however, it is presently most advanced in its applications for cancer. Therefore, in this article, we will use cancer as an indication to discuss the challenges in clinical translation of nanomedicines. Indeed, using nanotechnology to uncap the full potential of existing chemotherapy agents has emerged as an attractive drug development strategy, and several nanotherapeutics are already being used in the clinic.1–2 This stems from the unique physicochemical properties of nanoparticles carrying chemotherapy, which can be facilely modulated to confer unique advantages over existing chemotherapeutic agents.3 Indeed, changing the size of a drug from Angstrom scale to the nanoscale can alter the pharmacokinetic profile of the molecule. Furthermore, it is well known that surface modifications to increase hydrophilicity can mask the nanovectors from the reticuloendothelial system, thereby increasing circulation time.3–5 Such nanovectors accumulate preferentially in tumors helped by the unique leaky tumor vasculature, which when coupled with impaired intratumoral lymphatic drainage contributes to an enhanced permeation and retention (EPR) effect.6,7 Indeed, these nanoparticles were found to deliver between 5–11-fold more doxorubicin, an anticancer drug, to Kaposi sarcoma lesions than to normal skin.8 Doxorubicin-loaded lipid-based nanoparticles are already being used clinically for treatment of breast cancer.9,10
Similarly, the integrated area under the tumor paclitaxel concentration-time curve was found to be 33% higher when administered as an albumin protein-paclitaxel complex nanoparticle, which is currently approved for use in metastatic breast cancer, than when administered as free paclitaxel.11 Interestingly, it should be kept in perspective that the drivers for developing these nanoparticles for delivering doxorubicin and paclitaxel were primarily to overcome off-target side effects, for example cardiotoxicity in the case of doxorubicin, or hypersensitivity to the vehicles used for delivering taxanes.12,13 These advantages arose from the preferential delivery of anti-cancer drugs to the tumor and limited penetration into normal tissue or were due to the fact that the nanoparticle suspension removed the need for biologically incompatible vehicles. However, it is unlikely that an approach of developing nanomedicines to ameliorate the side effects of a chemotherapeutic will translate to the clinic today without a clear efficacy advantage. This article discusses the challenges that nanomedicines face and the potential approaches to overcome these hurdles toward their clinical translation.
Is increased delivery of a drug to the tumor enough to confer efficacy advantage? The potential of using nanoparticles to achieve increased intratumoral concentrations of cytotoxic agents as a result of the enhanced permeation and retention effect spurred the
Shiladitya Sengupta, Brigham and Women’s Hospital and Harvard Medical School; [email protected]
Data Loading...
