Nanomaterials: Versatile Drug Carriers for Nanomedicine
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large classes of therapeutic agents for cytotoxic activity, small interference RNA
(siRNA), chemosensitizers, and antiangiogenic agents. A generalized overview of
some nano-vehicles for release of drug which aims to progress the pharmacokinetics,
pharmacodynamics, and bioavailability of drugs summarizes in Table 1.
Drug targeting, maintaining the therapeutic effect with a reduction in cytotoxicity
and biocompatibility are the primary goals of drug delivery systems (DDS) [8]. The
nanoscale carriers have upgraded the DDS. Thus comprises different biocompatible
and biodegradable materials such as natural or synthetic materials [18]. At present,
very few DDS has been approved by the FDA, and many are being studied in drug
delivery. Here, we discuss the approaches to enhance the drug delivery systems based
on drug targeting, controlled drug release, multidrug resistance, and multifunctional
nano-carriers.
4 Drug Targeting
The synthesis of nanoparticles with an effective drug delivery system is one of the
main challenges faced in the development process. Thus achieved with two critical
functions by the DDS-evading host immune response and reaching their predetermined targets. Nanoparticles can be classified based on the potentiality to locate and
drug delivery to the target area of the body as a passive and active target.
Intravenous drug delivery tends to disperse evenly in the body. Where the take-up
ability of individual-sized particles by the tumor cells is to a greater extent than that
of the healthy normal cells because of the combination of faulty particle screening
and leaky tumor blood vessels, this phenomenon is known as enhanced permeability
and retention (EPR) effect showing mechanism for passive targeting [19].
The properties of nanoparticles, such as particle size, shape, and surface charge,
influences the EPR effect, which in return helps in circulation time, intracellular
internalization, and penetration speed. For instance, phagocytic cells can uptake
larger particles, while nonphagocytic cells prefer smaller particles for uptake [21].
Hence, due to the EPR effect, nanoparticles that encapsulate drugs get accumulated
in the tumor at higher concentrations (5–10 times) as compared to healthy tissues
within 1–2 days [22]. For example, FDA approved Doxil® (a PEG-coated liposomal system containing Doxorubicin delivery for cancer therapy), and Abraxane®
(paclitaxel-coated with albumin nanoparticles for the metastatic breast cancer) tend
to circulate in the body with longer (100 times) half-life with reducing systemic toxicity simultaneously than that of the free anticancer drugs [23]. The surface charge of
the nanoparticles plays an essential role in blood circulation and the internalization
of the cell. Negatively surface charged NPs will circulate in the blood for a more
extended period while the NPs with a positive charge are more readily uptaken by
the cancer cells (due to negative surface charge) [24].
EPR effect is not feasible for targeting cancer cells in all tumors, due to different
porosity of tumor vessels and the degree of vascularization. Passively targeted NPs
fails more than 95% to reach the cancer cells when injected intravenously, thus
257
large classes of therapeutic agents for cytotoxic activity, small interference RNA
(siRNA), chemosensitizers, and antiangiogenic agents. A generalized overview of
some nano-vehicles for release of drug which aims to progress the pharmacokinetics,
pharmacodynamics, and bioavailability of drugs summarizes in Table 1.
Drug targeting, maintaining the therapeutic effect with a reduction in cytotoxicity
and biocompatibility are the primary goals of drug delivery systems (DDS) [8]. The
nanoscale carriers have upgraded the DDS. Thus comprises different biocompatible
and biodegradable materials such as natural or synthetic materials [18]. At present,
very few DDS has been approved by the FDA, and many are being studied in drug
delivery. Here, we discuss the approaches to enhance the drug delivery systems based
on drug targeting, controlled drug release, multidrug resistance, and multifunctional
nano-carriers.
4 Drug Targeting
The synthesis of nanoparticles with an effective drug delivery system is one of the
main challenges faced in the development process. Thus achieved with two critical
functions by the DDS-evading host immune response and reaching their predetermined targets. Nanoparticles can be classified based on the potentiality to locate and
drug delivery to the target area of the body as a passive and active target.
Intravenous drug delivery tends to disperse evenly in the body. Where the take-up
ability of individual-sized particles by the tumor cells is to a greater extent than that
of the healthy normal cells because of the combination of faulty particle screening
and leaky tumor blood vessels, this phenomenon is known as enhanced permeability
and retention (EPR) effect showing mechanism for passive targeting [19].
The properties of nanoparticles, such as particle size, shape, and surface charge,
influences the EPR effect, which in return helps in circulation time, intracellular
internalization, and penetration speed. For instance, phagocytic cells can uptake
larger particles, while nonphagocytic cells prefer smaller particles for uptake [21].
Hence, due to the EPR effect, nanoparticles that encapsulate drugs get accumulated
in the tumor at higher concentrations (5–10 times) as compared to healthy tissues
within 1–2 days [22]. For example, FDA approved Doxil® (a PEG-coated liposomal system containing Doxorubicin delivery for cancer therapy), and Abraxane®
(paclitaxel-coated with albumin nanoparticles for the metastatic breast cancer) tend
to circulate in the body with longer (100 times) half-life with reducing systemic toxicity simultaneously than that of the free anticancer drugs [23]. The surface charge of
the nanoparticles plays an essential role in blood circulation and the internalization
of the cell. Negatively surface charged NPs will circulate in the blood for a more
extended period while the NPs with a positive charge are more readily uptaken by
the cancer cells (due to negative surface charge) [24].
EPR effect is not feasible for targeting cancer cells in all tumors, due to different
porosity of tumor vessels and the degree of vascularization. Passively targeted NPs
fails more than 95% to reach the cancer cells when injected intravenously, thus