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The field of nanotechnology now has pivotal roles in electronics, biology and medicine. Its application can be appraised, as it involves the materials to be designed at atomic and molecular level. Due to the advantage of their size, nanospheres have been shown to be robust drug delivery systems and may be useful for encapsulating drugs and enabling more precise targeting with a controlled release. In this review specifically, we highlight the recent advances of this technology for medicine and drug delivery systems.
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REVIEW
Nanomedicine and drug delivery: a mini review
Agha Zeeshan Mirza Farhan Ahmed Siddiqui
Received: 24 October 2013 / Accepted: 23 January 2014
ÓThe Author(s) 2014. This article is published with open access at Springerlink.com
Abstract The field of nanotechnology now has pivotal
roles in electronics, biology and medicine. Its application
can be appraised, as it involves the materials to be designed
at atomic and molecular level. Due to the advantage of
their size, nanospheres have been shown to be robust drug
delivery systems and may be useful for encapsulating drugs
and enabling more precise targeting with a controlled
release. In this review specifically, we highlight the recent
advances of this technology for medicine and drug delivery
systems.
Keywords Drug delivery Nanotechnology Inorganic
nanoparticles Organic nanoparticles
Nanoparticles
Nanoparticles are organic or inorganic structures (sizes
1–100 nm) similar to antibodies and DNA plasmids [13].
Significant work has been done in past decades in the field
of nanotechnology; now it is possible to fabricate, char-
acterize, and modify the functional properties of nanopar-
ticles for medical diagnostics and biomedical applications
[410]. Nanobiotechnology bridges the physical and bio-
logical sciences [11], with applications of nanophase and
nanostructures in different areas of science, especially in
biomedicine, in which these objects are of great interest
[1216]. Nanoparticles are influencing the field of medi-
cine from nanobiotechnology, microfluidics, biosensors,
drug delivery, and microarrays to tissue micro-engineering
[17]. Metal, organic and polymeric nanoparticles and lip-
osomes are commonly studied and can be designed for the
site-specific delivery of drugs (Fig. 1)[18] especially those
drugs which have poor solubility and absorption [19,20].
Nanoparticles for drug delivery
The most promising application of nanomaterials is the
promise of targeted, site-specific drug delivery. The
potential of eliminating a tumorous outgrowth without any
collateral damage through nanomaterial-based drug deliv-
ery has created significant interest and nanoparticles form
the basis for bio-nano-materials [3] and major efforts in
designing drug delivery systems are based on functional-
ized nanoparticles [21,22]. Initially, they were devised as
carriers for vaccines and anticancer drugs [23] and then the
nanometer size ranges may significantly enhance the drug
delivery by affecting the bio-distribution and toxicody-
namics of drugs [24,25]. This can make in vivo delivery of
many types of drugs which pose serious delivery problems,
a relatively easy task [26]. Modifying or functionalizing
nanoparticles to deliver drugs through the blood brain
barrier for targeting brain tumors can be regarded as a
brilliant outcome of this technology [27]. For example,
doxorubicin does not cross the blood–brain barrier, but its
integration with polysorbate 80 modified polybutylcyano-
acrylate nanoparticles can increase its delivery to the brain
to a significant extent [28]. Due to their size, shape and
functionality, nanoparticle systems play a pivotal role in
creation of DNA delivery vectors [29]. They can penetrate
deep into tissues and are absorbed by the cells efficiently
A. Z. Mirza (&)
Department of Chemistry, University of Karachi, Karachi 75270,
Pakistan
e-mail: dr.zeeshan80@gmail.com
F. A. Siddiqui
Faculty of Pharmacy, Federal Urdu University of Arts, Science
and Technology, Karachi 75300, Pakistan
123
Int Nano Lett (2014) 4:94
DOI 10.1007/s40089-014-0094-7
[30]. Nano-sized colloidal carriers of drugs can be regarded
as an advanced development in pharmacotherapy [31].
They act as potential carriers for several classes of drugs
like anti-cancer, anti-hypertensive and hormones, etc. [18].
Submicron colloidal particles have been used as nanopar-
ticles for the purpose of drug delivery [32] and also used
for the diagnosis of diseases [26]. Nanoparticles have
widened the scope of pharmacokinetics for insoluble drugs.
For example, the trans-retinoic acid nanoparticle coated by
CaCO
3
was developed as a new drug delivery system,
which on spray drying formed aggregates. The aggregates
thus formed were found to re-disperse in water, which
stimulated insulin secretion from islets [33]. Generally,
nanoparticle may be composed of polymeric or inorganic
materials. Some important examples from literature are
reviewed in the following sections.
Polymeric nanoparticle
Polymeric nanoparticles are made from biocompatible and
biodegradable materials and a variety of natural (gelatin,
albumin) and synthetic polymers (polylactides, poly-
alkylcyanoacrylates) [32] are considered as the most
promising drug carrier as compared to liposomes [34].
Polymers as host material play a significant role in metals
[3436] and semiconductors [3740] nanoparticles. These
nanoparticles are designed as drug carrier with the objec-
tive of delivering active molecules to the intended target
[41]. Polymers are filled with dispersed nano-fillers
(smaller than 100 nm) in nano-composites [42]. Polymer
hydrophobicity, nanoparticle area and monomer concen-
tration affect the adsorption capacity of the drug [43].
During polymerization, drugs may be added and be
entrapped within the nanoparticle polymer network. Prob-
lems of drug bioavailability can be solved with nanotech-
nology. To improve drug absorption and bioavailability of
hydrophobic drugs (paclitaxel or 5-fluorouracil) nano-scale
cavities with liposomes or encapsulated polymers can be
designed which can metabolize drugs at optimum rates for
desired therapeutic effect in target tissues [4446]. Nano-
capsules can be synthesized using polymers or from albu-
min and liposomes [24].
There are several polymers available for the synthesis of
nanoparticles. Polylactide–polyglycolide copolymers,
polyacrylates and polycaprolactones, etc. are synthetic
polymers whereas albumin, gelatin, alginate, collagen and
chitosan used as natural polymers [25]. Polylactides and
poly (DL-lactide-co-glycolide) polymers undergo hydro-
lysis upon implantation, form biologically compatible
Fig. 1 Example of metal nanoparticles, dendrimers, peptide-based nanoparticles, liposomes, carbon nanotubes and quantum dots
94 Page 2 of 7 Int Nano Lett (2014) 4:94
123
fragments, and are mostly investigated for drug delivery
[47]. It is apparent that chemical conjugation of drugs with
different polymers provides opportunities to increase their
activities. Jie et al. synthesized amphiphilic N-(2-hydroxy)-
propyl-3-trimethylammonium-chitosan-cholic acid poly-
mers by joining cholic acid and glycidyl trimethyl
ammonium chloride onto chitosan and self-assembled into
nanoparticles in phosphate-buffered saline. Doxorubicin
could be encapsulated into these nanoparticles and then
could easily be uptaken by breast cancer (MCF-7) cells and
released into the cytoplasm [48]. Shengtang et al. synthe-
size folic acid-conjugated chitosan–polylactide copolymers
to build a drug carrier with active targeting of paclitaxel.
Targeting characteristic was confirmed using folic acid
receptor-expressed MCF-7 breast cancer cells [49]. One
research described the fabrication of quatemized
poly(propylene imine) dendrimer of generation-3, QPPI
(G3) as a drug carrier for poorly soluble anti-inflammatory
drug nimesulide and an improvement in solubility of drug
was observed [50]. Abdullah et al. [51] encapsulated nano-
scaled emulsion containing ibuprofen with carbopol 934,
940 and ultrez 10 as viscosity modifiers. Behbehani et al.
[52] observed the effect of silica nanoparticles on the
activity of a-amylase. Park et al. [53] reported that glycol
chitosan-based nanoparticles of adriamycin are useful for
sustained and specific delivery of adriamycin, thus showing
lower cytotoxicity than adriamycin alone.
Release of drugs from nanoparticles and biodegradation
are important parameters to be considered for developing
successful formulations. Therefore, the diffusion charac-
teristics and breakdown properties of the nanoparticles at
the drug delivery site need to be carefully mapped to
achieve effective therapeutic capabilities [54].
Inorganic nanoparticles
Nanoparticles offered important multifunctional platforms
for biomedical applications. Varieties of nanoparticles,
such as silica nanoparticles [55], quantum dots [56,57],
metal nanoparticles [58] and lanthanide nanoparticles [59,
60], have unique properties which are adapted for different
applications in the bio-analysis field.
A nanoparticle does not only indicate drug delivery but
confirmation of target delivery is also important. Tracking
of nanomedicine from the systemic to sub-cellular level
becomes essential. Many florescent markers are available;
however, nanoparticles have not only advantage of show-
ing improvement in fluorescent markers for medical
imaging and diagnostic applications but also in imaging of
tumors and other diseases in vivo [61]. For example, Lee
et al. synthesized Fe
3
O
4
nanocrystals on uniform dye-
doped mesoporous silica nanoparticles to be used as a
contrast agent in magnetic resonance imaging and loaded
doxorubicin in the pores. This system has great potential as
probes in magnetic resonance and fluorescence imaging
and doxorubicin was successfully delivered to the tumor
sites and its anticancer activity was retained [62]. Simi-
larly, histidine-tagged cyan fluorescent protein-capped
magnetic mesoporous silica nanoparticles system was
fabricated for drug delivery and fluorescent imaging [63].
Quantum dots are small-sized (1–10 nm) semiconductor
nanocrystals composed of inorganic elemental core (e.g.,
Cd and Se) surrounded by a metallic shell (ZnS). They are
widely used in biological research and can also be used as
drug carriers or simply as fluorescent labels for other drug
carriers [56,57]. Among the broad diversity of nanoparti-
cles, iron oxide and gold nanoparticles are the most
intensively studied [64]. Due to the presence of surface
plasmons, gold, copper and silver nanoparticles strongly
absorb light in the visible region, making it possible to
study their size-dependent light absorption through surface
plasmon resonance (SPR). Gold nanoparticles and nano-
rods have many unique properties, which have been
explored for potential applications in bio-molecular
detection (Fig. 2)[65]. In terms of biocompatibility and
non-cytotoxicity, gold nanoparticles as approved by the
FDA have distinct advantages over other metallic particles
and could also be utilized as a favorable carrier for delivery
of drugs [66]. These nanoparticles can be conjugated with
amino acid [67] and proteins [68]. Fabrication of gold
nanoparticles and functionalization with organic molecules
to interact with any physiological system are more
important [6971]. These functionalized nanoparticles are
a promising candidate for drug delivery as biomarkers of
drug resistance cancer cell [72]. Reported application of
gold nanoparticles includes insulin delivery by nasal route
[73], improved antimicrobial action against E. coli strains
[74] and ciprofloxacin-protected nanoparticles [75]for
better drug release. Dhar et al. [64] reported a method for
synthesis of gold nanoparticles using natural, gellan gum
for the delivery of doxorubicin hydrochloride and demon-
strated the successful loading of doxorubicin onto gold
nanoparticles. Similarly, Gibson et al. [76] defined a very
accurate measurement of biological activity by well-
defined preparation of gold drug nanoparticle system. Hwu
et al. [72] synthesized three paclitaxel-conjugated nano-
particles using Fe
3
O
4
and gold as the core. These conju-
gated nano-materials comprise a new class of candidates as
anticancer drugs. Our group has investigated synthesis and
functionalization of gold nanoparticles [77]. We have
functionalized gold nanoparticles with different anticancer
drugs for target drug delivery and also as reducing and
capping agents for gold nanoparticle synthesis. As such, the
applications are very broad and useful for the release of
different biologically active molecules. Recent work by us
Int Nano Lett (2014) 4:94 Page 3 of 7 94
123
suggested that Au NPs-Au NRs complexes can also be used
for further attachment of drugs and biomolecules for
potential-targeted drug delivery [78]. Our research indi-
cated that the surface modification can enhance the stability
of Au NRs and we can use Au NRs as multiplex biosen-
sors. Our focus was on the development of nanoparticles
for bio-sensing and targeted drug delivery for cancer
therapeutics. We developed folic acid and doxorubicin-
tagged nanoparticles through a novel chemical linking
protocol and tagged folic acid and doxorubicin on different
planes of the nanorods. In this configuration, the nanorods
can potentially target cancer cells very selectively and then
deliver a cancer drug with high efficiency. An investigation
of biological activity of this system is ongoing and will be
reported.
Nanoparticle characterization can be performed by
measuring the following parameters as particle size, sur-
face charge, surface functionality and optical and magnetic
properties. Formation of nanoparticles is demonstrated
using surface plasmon resonance by the UV–Vis–NIR
absorption spectra (Fig. 3). The most commonly used
techniques to measure nanoparticles size are transmission
electron microscopy (TEM) and scanning electron
microscopy (SEM). The zeta potential of a particle is used
Fig. 2 a TEM images of gold
nanoparticles, bnanorods,
cSEM images of nanoparticles
Fig. 3 Visible-NIR spectra of
gold nanoparticles (a) and
nanorods (b)
94 Page 4 of 7 Int Nano Lett (2014) 4:94
123
to establish the colloidal stability of nanoparticles and it
also gives the complete picture of overall charges. More-
over, it can also help in formulating the more stable
nanoparticles product by shedding information on the
effect of various parameters as pH, concentration of an
additive or ionic strength of the medium on it [79,80].
Conclusion
Nanoparticles are rapidly becoming the focus of most
efforts aiming at targets and site-specific drug delivery. The
targeting ability of nanoparticles depends on certain factors
such as particle size, surface charge, surface modification
and hydrophobicity. Still many problems related to selec-
tive binding, targeted delivery and toxicity need to be
overcome. Limited knowledge about the toxicity of nano-
particles is a major concern and certainly deserves more
attention. If these nanoparticles are cautiously designed to
tackle problems related to target and route of administra-
tion, they may lead to a new more successful paradigm in
the world of therapeutics and research. The most promising
research in nanoparticle production is via using supercrit-
ical fluids which are environmental friendly and free of
toxic solvents. Much research is currently being performed
to overcome these hurdles which will definitely establish
nanoparticle-based drug delivery as the gold standard for
site-specific therapeutics.
Conflict of interest The authors declare that they have no com-
peting interests.
Authors’ contributions AZM surveyed and drafted the review
article. All authors read and approved the final review.
Open Access This article is distributed under the terms of the
Creative Commons Attribution License which permits any use, dis-
tribution, and reproduction in any medium, provided the original
author(s) and the source are credited.
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... Encapsulation in adequately designed delivery vehicles has been the most prominent research paradigm to overcome the shortcomings of lipophilic phytochemicals solubility, bioavailability and alter the drug pharmacokinetics to achieve desired therapeutic efficacy and safety [9]. The field of biomedicine integrating nanobiotechnology, drug delivery and tissue engineering have been incited by nanoparticles [10]. Polymeric nanoparticles with diameters ranging from 10 to 1000 nm possess properties that make them desirable for use as a delivery vehicle. ...
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... Nanotechnology encompasses innovative tools dedicated to the design, synthesis, and application of materials with at least one dimension at the nanoscale (or one billionth of a meter, usually 0.1-100nm) [1][2][3][4]. Because of their size and surface area/mass ratio, nanomaterials display unique chemical, electronic, optical, and magnetic properties, which can be useful for biomedical applications such as drug delivery systems and biological molecular probes [1,[5][6]. ...
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In a world struggling to face the disruptive consequences of global warming, developing new energy conversion and storage solutions is of fundamental importance. This PhD thesis focuses on emerging heterostructures based on Indium Tin Oxide nanocrystals (ITO NCs) and two-dimensional Transition Metal Dichalcogenides (2D TMDs) for innovative light-driven optoelectronic nanodevices and energy storage solutions, combining the harvesting, conversion and storage aspects into a unique hybrid nanomaterial. Doped Metal Oxide (MO) NCs are attracting growing interest as nano-supercapacitors due to their ability to store extra charges in their electronic structure with record-high values of capacitance. Remarkably, these materials can be charged with light (i.e., photodoping), a process at the core of this project and so far not understood electronically. Here, the fundamental features involved in the charge accumulation process are investigated and the physics of photodoping explained. Complete control over energetic band bending and depletion layer engineering is demonstrated, exposing the key role of electronically depleted layers in core-shell NCs. Light-induced depletion layer modulation and band bending is the main mechanism responsible for the storage of extra charges in doped MO supercapacitors. Moreover, multi-electron transfer reversible reactions were observed in photodoped NCs when exposed to a frequently used electron acceptor. The coupling between ITO NCs and 2D TMDs allowed the implementation of a novel all-optical localized charge injection scheme for the manipulation of unperturbed 2D materials. Hybrid 0D-2D heterostructures proved all-solid-state photodoping possible, with promising charging dynamics and capacitance values. Theoretical modeling tools were developed, leading to the optimization of the charge storage capacity of 0D NCs. This work is of particular interest for the fabrication of the next-generation of nanostructured light-driven supercapacitors.
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Chapter
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Chitosan was conjugated with folic acid (FA) and the resulting chitosan derivatives with a FA-substitution degree of around 6 % was used to synthesize FA-conjugated chitosan–polylactide (FA–CH–PLA) copolymers to build a drug carrier with active targeting characteristics for the anticancer drug of paclitaxel (PTX). Selected FA–CH–PLAs with various polylactide percentages of about 40 wt% or lower were employed to fabricate nanoparticles using sodium tripolyphosphate as a crosslinker, and different types of nanoparticles were endued with similar average particle-sizes located in a range between 100 and 200 nm. Certain types of PTX-loaded FA–CH–PLA nanoparticles having encapsulation efficiency of around 90 % and initial load of about 12 % were able to release PTX in a controlled manner with significant regulation by polylactide content in FA–CH–PLAs. Targeting characteristic of achieved nanoparticles was confirmed using FA-receptor-expressed MCF-7 breast cancer cells. The uptake of PTX revealed that optimized FA–CH–PLA nanoparticles with an equivalent PTX-dose of around 1 μg/mL could have more than sixfold increasing abilities to facilitate intracellular paclitaxel accumulation in MCF-7 cells after 24 h treatment as compared to free PTX. At a relatively safe equivalent PTX-dose for normal MCF-10A mammary epithelial cells, the obtained results from Hoechst 33342 staining indicated that optimized PTX-loaded FA–CH–PLA nanoparticles had more than threefold increasing abilities to induce MCF-7 cell apoptosis in comparison to free PTX.
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This study describes the demonstration of quaternized poly(propylene imine) dendrimer of generation-3, QPPI (G3) as a drug carrier for poorly soluble drug nimesulide (NMD, an anti-inflammatory drug). QPPI (G3) was prepared by treating the surface amine groups of poly(propylene imine) dendrimer with glycidyltrimethyl ammonium chloride and it was characterized with FTIR, (1)H and (13)C NMR and MALDI-TOF mass spectral techniques. The drug carrying potential of QPPI (G3) was assessed by analyzing drug solubility, in vitro release and cytotoxicity studies. The observed results reveal that the aqueous solubility of NMD has been dramatically increased in the presence of QPPI (G3) and also can sustain the release of NMD. It is further noticed that the complexation of NMD with QPPI (G3) is responsible for increased solubility and sustained release. This complexation was evidenced through NMR ((1)H & 2D) and UV-vis spectral techniques, DSC and DLS studies. Cytotoxicity study through MTT assay on Vero and HBL-100 cell lines reveal that this dendrimer increase the biocompatibility and the tolerance concentration of NMD in drug-dendrimer formulations. The observed results prove that the QPPI (G3) is one of the new promising candidate for effective delivery of NMD.
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A robust functionalized procedure for gold nanorods (Au NR) with mercaptoundecanoic acid (MUA), which are assembled with nanoparticles, has been reported in the present work. The self-assembled nanostructures were characterized by UV–Vis-NIR spectrophotometer and transmission electron microscopy (TEM). Self-assembly procedures, governed by surface chemistry, indicated that chemical reactivity of nanomaterial may contribute in construction of potential nanoscale assemblies. These nanostructures have striking applications as single-molecule detection, plasmonics, and sensing.
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Uniformly dispersed amorphous nanoparticles of magnetite in polyvinyl alcohol have been obtained by ultrasound radiation. The properties of the as-prepared composite material were characterized by various analytical methods. We have found that the magnetite particles that were 12–20 nm in diameter were very well dispersed in the PVA. The magnetization measurements establish that the composite material is superparamagnetic in nature.