Biomedical Engineering Reference
In-Depth Information
5.6.2 Uptake by Nonphagocytic Cells
Uptake of NMs by nonphagocytic cells such as tumor cells can also happen if par-
ticles are <500 nm.
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Nonphagocytic internalization of nano-enabled drugs into
the target cells can occur macropinocytosis, clathrin-mediated endocytosis, and
non-clathrin-mediated endocytosis in such a way that as particle size increased,
internalization decreases. Cellular uptake was not observed for particles >500 nm.
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5.6.3 Uptake by Drug-Resistant Cancer Cells
Overcoming drug resistance in cancer chemotherapy by using NMs as delivery
systems is a very hot area of research in this century. Various mechanisms that
have been proposed include enhanced intracellular concentration of the drug by
endocytosis,
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inhibition of multidrug resistance (MDR) proteins by carrier com-
ponent materials such as Pluronic block copolymers,
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,
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promotion of other
uptake mechanisms such as receptor-mediated cellular internalization,
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adhe-
sion of NMs to the cell surface and increased drug concentrations at the vicinity
of target cancer cells.
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Furthermore, both drug and inhibitors of MDR proteins
can be incorporated into the same carriers for simultaneous delivery to the cancer
cells. For example, dox and cyclosporin A encapsulated in polyalkylcyanoacry-
late NPs have been demonstrated to reverse resistance synergistically.
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5.7 DRUG RELEASE AND BIODEGRADATION
Drug release refers to the process by which the drug loaded in or on the NMs is
released in the body through diffusion or dissolution of the NMs matrix releas-
ing the drug in solution. Biodegradation refers to the process by which the drug
delivery system is broken down inside the body.
Both drug release and biodegradation are important to consider when
developing an NMs drug delivery system. Ordinarily, effectiveness of drugs
is dependent not only on its active components but also on its solubility and
diffusion. When the drug is delivered using an NMs delivery system, effective-
ness is affected by parameters such as the particle size, release process which
is in turn affected by the biodegradation of the particle matrix. The smaller the
particles, the larger the surface area-to-volume ratio; therefore, most of the drug
associated with small particles would be at or near the particle surface which
leads to faster drug release. In contrast, larger particles have large cores, which
allow more drugs to be encapsulated per particle and give slower release. Thus,
control of particle size provides a means of tuning drug release rates.
5.7.1 Factors Affecting Drug Release
In general, the drug release rate depends on: (1) drug solubility, (2) desorption
of the surface-bound or adsorbed drug, (3) drug diffusion out of the NM matrix
into the body, (4) NM matrix erosion or degradation, and (5) the combination of
