The first application of regenerative medicine highlighted in the article is bone regeneration and repair. Currently, the only effective method of stimulating bone re-growth after an injury is taking a piece of the patient’s own bone and transplanting it to the site through a very painful procedure. These bone losses or defects which demand painful transplants are fare from uncommon and affect over 20 million people annually.1 According to the article, this has fueled an interest in targeting areas of injury with therapeutic agents such as growth factors and cytokines which are naturally involved in the bone regrowth signaling cascade to promote bone repair at the site of injury without painful transplant.1 However, the short half life of these proteins combined with the toxicity caused by repeated administrations demonstrate a significant roadblock for this method of bone regrowth and repair. This article highlighted that the favorability of nanoparticle-based delivery systems is due to the enhancement of the pharmacokinetics of the therapeutic particle encapsulated or attached to the polymer, as discussed in Professor Zhou’s recent lectures. Pharmacokinetics of a drug or therapeutic particle are a description of the movement of these materials through the body. Often, the pharmacokinetics of a drug present a significant barrier to their effective administration to treat disease as they may have limited stability or solubility. The example utilized in class was glyburide, a potential treatment for stroke patients which was constrained by its limited solubility and high degradation rates which necessitated continuous brain injection over 3 days for effective treatment. Professor Zhou highlighted that nanoparticles facilitated the release of glyburide in a way that limits degradation and eliminates the need to pump the drugs directly into the brain by generating nanoparticles which are specifically engineered to penetrate the brain. Thus, as Professor Zhou stressed this week, nanoparticles are a powerful method of changing the pharmacokinetics of a drug to make it suitable for clinical applications. According to the article, the growth factors which could naturally allow for bone regrowth and regeneration are extremely degradable within the body and an almost toxically high level of these proteins need to be injected in order for them to have any appreciable effect. The use of nanoparticles is highlighted in the article as an interesting approach to this pharmacokinetics problem because they are capable of deep tissue penetration and have extremely tunable properties such as solubility, diffusivity and release characteristics. First, the review article highlights the stimulation of human mesenchymal stem cells with PLGA-encapsulated growth factor proteins to successfully promote osteogenesis in a recent study. Additionally, the effective administration of growth factor rhBMP-2 was enhanced through PEGgylation of the protein, which facilitated enhanced bone formation in rats. I believe these technologies represent a valuable method of harnessing the bodies natural regrowth and remodeling potential to cut down on toxically high doses of therapeutics and painful surgeries. This opinion that nanoparticles may be effective in enhancing drug administration is supported by the in-class example of improved pharmacokinetics of glyburide in treating stroke.
References
(1) Van Rijt, Sabine, and Pamela Habibovic. “Enhancing Regenerative Approaches with Nanoparticles.” Journal of the Royal Society Interface 14.129 (2017): 20170093. PMC. Web. 30 Sept. 2018.
