286
A. S. Shinde et al.
testing of nanomedicine on the normal development of inflammatory responses and
innate immunity is the key while accessing the immune safety profile of nanodrug.
With all the complexity, different in vitro and in vivo models should be studied thoroughly for its immune system reactions. For this, representative and specific assays
are needed to be designed. But the laboratory models provide limited knowledge and
information for potential immune response in human subjects. In several cases, there
is no molecular correlation found between immune reactions in human versus mice,
where alternate molecular pathways have been used [180]. For example, cell lines are
mostly transformed or tumor-derived. Thus, the NPs cytotoxicity on highly proliferating macrophage cell lines may not reflect what has its toxic effect on noncycling
primary resident macrophages cells.
On the other hand, NPs can induce TNF-α and yield similar results in continuous
versus primary macrophages. Thus, cell lines are beneficial for rapid and reproducible testing only for validating biomarkers, which reflect normal human cell
responses. In vivo experimental models are also required to understand and study
the systemic immune reactions. Genetically modified mice for the immunity system
deliver straightforward answers for potential activation of the immune system by
the NPs. The target delivery for protected organs like CNS, in vivo models, are
mandatory. Blood circulation is the ideal way to deliver NPs to the CNS. Polymeric
nanoparticles or coating with PEG have been used to cross BBB [181]. The nanomaterials used as biomedicine can be synthesized to target or avoid the immune system.
Thus, there is a need for the evolution of new nanomaterial-mediated approaches and
assays to help to justify the results obtained from different methods.
25 Conclusions
In the last few years, the scientist has developed several new technologies for the
diagnostics and treatment of various diseases. The use of nanotechnology in the development of nanocarriers as DDS has shown high potential in research. Nano-DDS
presents unique advantages which have proven to have enhanced intracellular uptake
as compared to the other conventional drug forms. Ligands such as antibodies that are
conjugated to nanocarriers are favored in a targeted therapeutic approach because of
the better-controlled therapy where delivery of active drugs is achievable in smaller
amounts at the required sites in the body. Building upon these advances towards
human clinical trials, much work is needed to be done in over the next 5–10 years to
more fully realize the promise of nanomedicine. First, the logical design of nanomaterials and the development of tools is needed to design a detailed understanding of
biomedical processes required. For example, the targeting strategies for drug carrier
design may vary in type, developmental stage, and location of the disease. Second,
more complex DDS such as multi-functional NPs that are simultaneously are capable
of targeting, imaging, and treatment therapy, are the motif of future research. Third,
the main concern about these DDS is regarding their immune toxicity issues, which
A. S. Shinde et al.
testing of nanomedicine on the normal development of inflammatory responses and
innate immunity is the key while accessing the immune safety profile of nanodrug.
With all the complexity, different in vitro and in vivo models should be studied thoroughly for its immune system reactions. For this, representative and specific assays
are needed to be designed. But the laboratory models provide limited knowledge and
information for potential immune response in human subjects. In several cases, there
is no molecular correlation found between immune reactions in human versus mice,
where alternate molecular pathways have been used [180]. For example, cell lines are
mostly transformed or tumor-derived. Thus, the NPs cytotoxicity on highly proliferating macrophage cell lines may not reflect what has its toxic effect on noncycling
primary resident macrophages cells.
On the other hand, NPs can induce TNF-α and yield similar results in continuous
versus primary macrophages. Thus, cell lines are beneficial for rapid and reproducible testing only for validating biomarkers, which reflect normal human cell
responses. In vivo experimental models are also required to understand and study
the systemic immune reactions. Genetically modified mice for the immunity system
deliver straightforward answers for potential activation of the immune system by
the NPs. The target delivery for protected organs like CNS, in vivo models, are
mandatory. Blood circulation is the ideal way to deliver NPs to the CNS. Polymeric
nanoparticles or coating with PEG have been used to cross BBB [181]. The nanomaterials used as biomedicine can be synthesized to target or avoid the immune system.
Thus, there is a need for the evolution of new nanomaterial-mediated approaches and
assays to help to justify the results obtained from different methods.
25 Conclusions
In the last few years, the scientist has developed several new technologies for the
diagnostics and treatment of various diseases. The use of nanotechnology in the development of nanocarriers as DDS has shown high potential in research. Nano-DDS
presents unique advantages which have proven to have enhanced intracellular uptake
as compared to the other conventional drug forms. Ligands such as antibodies that are
conjugated to nanocarriers are favored in a targeted therapeutic approach because of
the better-controlled therapy where delivery of active drugs is achievable in smaller
amounts at the required sites in the body. Building upon these advances towards
human clinical trials, much work is needed to be done in over the next 5–10 years to
more fully realize the promise of nanomedicine. First, the logical design of nanomaterials and the development of tools is needed to design a detailed understanding of
biomedical processes required. For example, the targeting strategies for drug carrier
design may vary in type, developmental stage, and location of the disease. Second,
more complex DDS such as multi-functional NPs that are simultaneously are capable
of targeting, imaging, and treatment therapy, are the motif of future research. Third,
the main concern about these DDS is regarding their immune toxicity issues, which