294
11.4 Engineered Nanomaterials in Pharmaceuticals:
Biological and Environmental Interactions
The introduction and use of nanotechnology in the pharmaceutical industry exhibited remarkable potential and remarkable efforts are in progress worldwide to fulfill
the promise of the nanorevolution. Previously, nanotherapies were mainly used as
vaccine or cancer therapy, whereas recent trends toward engineering nanomaterials
as personalized medicine for the prevention of diseases by employing nanotherapeutics with other advanced nanotechnologies, such as nanobots and nanodevices
(Goswami et al. 2017).
The intervention dates back to 1930 when first nanoscale iron colloidal preparation was administered in human. It has been reported that currently there are 43
approved drug formulations commonly referred as nanomedicines, and approximately 789 clinical trials are ongoing pertaining to 25 devices and 122 therapeutics
(Weissig et al. 2014; Weissig and Guzman-Villanueva 2015). Milled nanocrystals
and liposomes were the first-generation products that used nanomaterials to enhance
bioavailability or drug exposure at action sites, respectively for poorly water- soluble
drugs. TRICOR
®
is an example that contains active ingredient (Fenofibrate) crystals
milled into the nanosize range (Tyner et al. 2015). The first approved new drug
application (NDA) was Gris-PEG (griseofulvin ultramicro size, <1000 nm) that targeted treatment of fungal infections. Further, the first US FDA-approved
nanotechnology- enabled product was Doxil
®
nanodrug (stealth liposomes encapsulating about 10,000 doxorubicin molecules) that came into being in 1995 for treating AIDS-related Kaposi’s sarcoma. Numerous unique features such as (i) increased
biodistribution, (ii) enhanced targeting, and (iii) potential of stimuli-sensitive
microenvironments payload release facilitated the development of nanotherapeutics
of huge antibody–drug conjugates, small-molecule platforms, polymeric nanoparticles, albumin nanoparticles, metal-based nanoformulations, etc. In vaccine therapy, virosomes (e.g., InflexalV
®
and Epaxal
®
), consisting of unilamellar phospholipid
membrane nanovesicles integrating virus-derived glycoproteins (100–150 nm) are
considered an efficient delivery system. In viral gene therapy, the European
Medicines Agency (EMA) in 2012 approved the first product for lipoprotein lipase
deficiency that used adeno-associated virus (AAV), allowing stable gene transfer
and enduring transgene expression. Various other products, such as aprepitant, fenofibrate, megasterol acetate, and rapamycin are being marketed using the NanoCrystal
®
or the DissoCube
®
technology.
The ever-increasing usage of engineered nanomaterials in pharmaceuticals has
provoked scientific community to question their possible negative effect on ecology
and animal health. Moreover, the unique properties of engineered nanomaterials
make them highly reactive (chemically and biologically), able to interact with the
neighboring matters including biological organisms as well as the environmental
components that results in toxicity as a result of biological and environmental
interactions.
D. Kundu et al.
11.4 Engineered Nanomaterials in Pharmaceuticals:
Biological and Environmental Interactions
The introduction and use of nanotechnology in the pharmaceutical industry exhibited remarkable potential and remarkable efforts are in progress worldwide to fulfill
the promise of the nanorevolution. Previously, nanotherapies were mainly used as
vaccine or cancer therapy, whereas recent trends toward engineering nanomaterials
as personalized medicine for the prevention of diseases by employing nanotherapeutics with other advanced nanotechnologies, such as nanobots and nanodevices
(Goswami et al. 2017).
The intervention dates back to 1930 when first nanoscale iron colloidal preparation was administered in human. It has been reported that currently there are 43
approved drug formulations commonly referred as nanomedicines, and approximately 789 clinical trials are ongoing pertaining to 25 devices and 122 therapeutics
(Weissig et al. 2014; Weissig and Guzman-Villanueva 2015). Milled nanocrystals
and liposomes were the first-generation products that used nanomaterials to enhance
bioavailability or drug exposure at action sites, respectively for poorly water- soluble
drugs. TRICOR
®
is an example that contains active ingredient (Fenofibrate) crystals
milled into the nanosize range (Tyner et al. 2015). The first approved new drug
application (NDA) was Gris-PEG (griseofulvin ultramicro size, <1000 nm) that targeted treatment of fungal infections. Further, the first US FDA-approved
nanotechnology- enabled product was Doxil
®
nanodrug (stealth liposomes encapsulating about 10,000 doxorubicin molecules) that came into being in 1995 for treating AIDS-related Kaposi’s sarcoma. Numerous unique features such as (i) increased
biodistribution, (ii) enhanced targeting, and (iii) potential of stimuli-sensitive
microenvironments payload release facilitated the development of nanotherapeutics
of huge antibody–drug conjugates, small-molecule platforms, polymeric nanoparticles, albumin nanoparticles, metal-based nanoformulations, etc. In vaccine therapy, virosomes (e.g., InflexalV
®
and Epaxal
®
), consisting of unilamellar phospholipid
membrane nanovesicles integrating virus-derived glycoproteins (100–150 nm) are
considered an efficient delivery system. In viral gene therapy, the European
Medicines Agency (EMA) in 2012 approved the first product for lipoprotein lipase
deficiency that used adeno-associated virus (AAV), allowing stable gene transfer
and enduring transgene expression. Various other products, such as aprepitant, fenofibrate, megasterol acetate, and rapamycin are being marketed using the NanoCrystal
®
or the DissoCube
®
technology.
The ever-increasing usage of engineered nanomaterials in pharmaceuticals has
provoked scientific community to question their possible negative effect on ecology
and animal health. Moreover, the unique properties of engineered nanomaterials
make them highly reactive (chemically and biologically), able to interact with the
neighboring matters including biological organisms as well as the environmental
components that results in toxicity as a result of biological and environmental
interactions.
D. Kundu et al.