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Targeted Materials

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Drug Delivery

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Abstract

The successful delivery of drug molecules to a desired tissue is contingent upon some degree of direct or indirect identification of that tissue by the drug dosage form. This can be approached from the perspective of engineering the material to be responsive to the environment either at the interface or surrounding the tissue. We discuss the first approach in this chapter and the second approach later in Chap. 7.

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Author information

Authors and Affiliations

  1. DuPont Central Research and Development, Wilmington, USA

    Eric P. Holowka

  2. School of Engineering and Applied Science, Harvard University, Cambridge, MA, USA

    Sujata K. Bhatia

Authors
  1. Eric P. Holowka
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  2. Sujata K. Bhatia
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Problems

Problems

  1. 5.1

    We have learned in this chapter that there are implications in solution properties to the change in the geometry of a self-assembly structure. This is apparent when comparing systems consisting of spherical versus tubular shapes, such as micelles, where there is a distinct difference in their respective aspect ratios (A f). If a biomedical engineer is designing an oral drug delivery system where the target tissue is the small intestine, answer the following questions with your knowledge of diffusion in self-assembled systems.

    1. (i)

      What are the relative viscosities of a spherical micelle (A f = 1) and a tubular micelle (A f = 50)?

    2. (ii)

      Which geometry micelle would you expect to be a more effective drug delivery system for the oral application described? Why?

    3. (iii)

      How would the percolation values differ for a spherical system relative to a fiber system?

    4. (iv)

      If the concentration of both the spheres and tubes is 7 mg/ml, do you think the colloid concentration would be in an acceptable range for this application for each respective shape? Why?

  2. 5.2

    The allergic response involves the aggregation of IgE receptor molecules within glycosphingolipid-cholesterol microdomains, known as lipid RAFTs, at the surface of mast cells to facilitate a process known as degranulation. If each RAFT domain consists of an average surface area of 0.031 μm2 relative and the mast cell is 20 μm in diameter with a cell membrane thickness of 5 nm and a Young’s modulus of 1.2 × 107 Pa, answer the following questions with your knowledge of the interaction surface area between elastic and hard materials.

    1. (i)

      Calculate the elastic modulus of the mast cell membrane assuming that E* is approximately equal to the bending energy (e bend) within a contact surface area of 0.01 μm2.

    2. (ii)

      A medical researcher would like to design a functionalized gold nanoparticle system to target a single RAFT domain on a mast cell. What would be the ideal particle radius if the pressure of the interaction between the nanoparticle and cell membrane is 1 × 10–10 Pa?

    3. (iii)

      What would the ideal nanoparticle radius be if the surface area of the RAFT domain doubled?

  3. 5.3

    A biomedical graduate student has designed a targeted vesicle system and is unsure of the possible mechanism of cellular internalization. If the vesicle system has a 50-nm diameter and is spherical in shape, answer the following questions with your knowledge of active and passive cellular delivery.

    1. (i)

      Based on the properties of this vesicle system, what mode(s) of cellular delivery would be preferred? Why?

    2. (ii)

      What is the vesicle size required to avoid lipid membrane fouling (ΔP = 8.75 × 107 ng/nm s2) assuming the pore size is 60 nm in diameter, the dynamic viscosity is 1 with a constant flux of 50 nm/s, and the filter area is represented by the surface area of the cell of 20-μm diameter and 5-nm membrane thickness?

    3. (iii)

      If you had to operate above the fouling limit, how would you increase the diffusive flux within the membrane?

    4. (iv)

      How long would it take to envelop the particle when D = 5 × 105 nm2/s and α = 1?

  4. 5.4

    A research lab in biomedical engineering wishes to design a micellar oral drug delivery system that effectively targets the heart. If the micellar system is 20 nm in diameter and charge-neutral, answer the following questions with your knowledge of self-assembled and targeted systems.

    1. (i)

      Discuss the sequence of physiological constraints in order as the oral drug passes from the mouth to the small intestine.

    2. (ii)

      Would changing the diameter of the nanoparticle from 20 to 200 nm affect the constraints of the oral delivery system? Why?

    3. (iii)

      Would changing the surface charge of the nanoparticle to one that is highly cationic affect the constraints of the oral delivery system? Why?

  5. 5.5

    Use the components in the following table and your knowledge of targeted and self-emulsifying drug delivery to determine the desired route of internalization for a vesicle system based on the criteria and physical limitations discussed in this chapter.

  6. (i)
    figure a

    Based on calculations of the thickness, curvature, and size of the self-assembled system, is it likely that it is internalized within the cell through an active or passive mechanism if the bending energy (e bend) is 5 × 106 Pa/m2and Young’s modulus is 1.2 × 107 Pa?

  7. (ii)

    What is the likely kinetics of binding from your answer to (i) if the rate constant for the binding of RGD receptors to the cell is 1.35 × 10–9 M?

  8. (iii)

    Do the characteristics of binding suggest that the binding force (F binding = 2 × 10–10 N) of the micelle system with a mass of 1 ng to the target cell type is possible relative to opposing forces (i.e., drag force) if the velocity of the system is 50 mm/s in blood plasma with a viscosity of 4cP, with an acceleration of 5 mm/s2? Why?

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Holowka, E.P., Bhatia, S.K. (2014). Targeted Materials. In: Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1998-7_5

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