Nanoparticles are poorly delivered
Nanoparticles have steadily been making their way into bio-medicine or nanomedicine over the past decade, with drug delivery being one of the areas that have seen the highest interest and development. An efficient drug delivery system should both retain the drugs within the vehicle and then subsequently release them when they are proximal to the desired location, and nanoparticles can accomplish this. However, in 2016, it was reported that only 0.7% of the introduced nanomedicine is eventually found in the targeted tumor. This leads to an inefficient clinical translation of nanomedicine mediated treatment and negatively affects manufacturing costs.
Smart nanoparticles
Liposomes and polymeric micelles are popular nanoparticulate tools for tumor-targeted drug delivery; however, both of these drug delivery systems speed up delivery via interaction with proteins in the blood, thus diminishing the quality of treatment. The ideal drug delivery system thus should release drugs actively, but only when stimulated.
Smart drug delivery systems are thus modifications to conventional nanoparticulate drug delivery tools. These can be used for targeted delivery that aids in the controlled and timely release of drugs and thus reduces toxicity in patients and improves the outcome of therapy.
Converting conventional nanoparticles to smart nanoparticles
The stimulation can be in the form of endogenous (pH, hormones, enzymes, biomolecules) or exogenous (temperature, magnetic field, ultrasound, radiation, electric pulse) stimuli. There are a variety of conventional nanoparticles that can be converted into smart drug delivery systems and are presented below.
Polymeric micelles:
Polymeric micelles have been pH-induced to mediate self-assembly of a conjugate drug that has been formulated to treat multidrug resistance (MDR) cancer. Ongoing research with glucose-responsive polymeric micelles might result in a treatment for diabetes. Opaxio by Cell Therapeutics, a polymeric drug activated by enzymes, targeted towards ovarian and lung cancer is in Phase III clinical trials.
Liposome formulations:
Liposome formulations have already been approved by the US FDA for clinical use, including Doxil for ovarian cancer and Depocyt for lymphocytic meningitis, among others.
ThermoDox, by Celsion Pharmaceuticals, is a heat-sensitive liposome nanomedicine targeting breast and liver cancers that is undergoing Phase III clinical trials. Temperature-triggered liposome deliveries also hold promise for the treatment of multidrug resistance in cancers.
Hybrid smart nanoparticles:
Organic-inorganic hybrid smart nanoparticles are made by hybridizing polymeric particles with nanometals like silica. The FDA-approved AuroLase therapy by Nanospectra BioSciences is a gold-silica conjugate stimulated by near-infrared radiation targeted at prostate cancer. Although in a nascent developmental stage, gold nanoparticle conjugates have been documented to combat multidrug resistance in cancer cells.
Exosomes:
Exosomes are nano-sized membrane vesicles that can be stimulated via endogenous or exogenous stimuli. This is a promising area of potential nanomedicine discovery, and the exosome-based drug delivery system exoCAT has been recently developed to treat Parkinson’s disease in a mouse model.
Conclusions
Smart drug delivery systems are becoming increasingly popular, as the administration of the drug can be adequately controlled, leading to better patient compliance. A total of 51 nanomedicines had been approved by the FDA by the year 2016, and many are currently approved for clinical trials.
Several aspects need to be evaluated for preclinical research to make the transition to the clinic. The endogenous stimuli used to trigger drug delivery tend to vary a lot among patients, hence these systems need to be optimized for reproducibility. Furthermore, the safety and therapeutic efficacy of the designed drug, along with the time frame for approval procedures, need to be evaluated.
