1) You have just been hired at a new start-up that has developed an intravenous
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Question
1) You have just been hired at a new start-up that has developed an intravenous (IV) injectable small molecule drug (OP145) to treat osteoporosis. During pre-clinical trials, it was discovered that OP145 led to unexpected negative side effects including nausea, vomiting and heart attacks. The chemical structure of OP145 is provided below: +H20 OP145 OP145 side products Fig. 1: OP145 structure is shown (10 points total) Based on Figure 1 and the provided information above, what are the likely causes of the pre-clinical trial results? a. b. (5 points total) As a new hire your boss expects you to use your biomaterials expertise to further improve the efficacy of OP145 and reduce the negative pre-clinical trial results. How would you use a drug delivery carrier to improve upon the limitations of OP145?Explanation / Answer
a. From figure 1 and the given data, we can see that OP145 produces side products because of its interaction with water. These side products are then responsible for the side effects during the pre-clinical trials. These side effects include nausea, vomiting and heart attacks. The side products of OP145 are phenylacetic acid and 2-Hydroxyphenyl acetate. These side products are only slightly soluble in water (making them accumulate in the body), and are known to show poisoning effects on high concentrations.
b. In order to improve the efficacy of OP145 and reduce the negative pre-clinical trial results, the best method is to avoid contact with water until the drug reaches its target. This can be achieved by using liposomal drug delivery carriers. Other useful options include polymeric micelles and microsphere, which may help to serve a similar purpose for drug delivery.
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