Keywords

3.1 Introduction

Efficient and targeted delivery of therapeutics to the desired location is a subject of substantial curiosity in chemotherapy. The administration of a therapeutic agent into the body might be toxic to many cell or tissue types; therefore delivering the drug specifically into the diseased cell without disturbing normal cells remains a major challenge in chemotherapeutics [1]. To address this fundamental task, significant effort has been and continues to be for the development of drug carriers which deliver chemotherapeutic drugs to the desired locations. Modern research attempts targeted drug delivery systems to overcome the limitations of conventional drug delivery system such as nonspecific bio-distribution and low therapeutic efficacy and inconvenient dosing (Fig. 3.1). Moreover, controlled release targeted drug delivery systems ensure cell/tissue specific targeting for a desired period of time leading to the minimization of drug side effects, higher therapeutic efficiency, and improved drug bioavailability. This method of approach has fascinated significant interest in the field of medicine since reducing drug consumption considerably reduces the effective cost of drug which in turn provides financial relief to the patients. As drug development is a both expensive and time-consuming process, scientists focused on drug delivery formulations which involve low cost research compared to discovering new drug candidates.

Fig. 3.1
figure 1

Conventional and targeted drug delivery systems. Reprinted with permission from [1] © 2002, Elsevier

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3.2 Targeted Drug Delivery

To achieve prolonged therapeutic efficacy researchers have developed different approaches to design delivery systems which continuously release the active ingredients over an extended time period after administration of single dose. Over the past three decades, sustained or controlled drug delivery systems (CDDS) have made significant progress in pharmaceutical formulations which offer several advantages over conventional therapy. CDDS maintain constant supply of therapeutic agent at—different intervals whereas sustained-release systems offer prolonged drug release at uniform intervals need not to maintain the same amount of drug release at every time.

An ideal controlled drug delivery system should offer the following features:

  1. 1.

    Predictable and prolonged drug release for extended durations

  2. 2.

    Better drug utilization, patient comfort, and compliance

  3. 3.

    It should maintain optimal drug plasma concentration with minimum fluctuation

  4. 4.

    It should enhance effective biological half-life of drugs

  5. 5.

    It should eradicate toxic side effects and frequent dosing.

A well designed drug delivery system deliver active pharmaceutical ingredient of desired concentration to the desired location for the accurate time and duration. The drug concentration should be within the therapeutic range, which is the concentration interval between the minimal effective concentration (MEC) and the minimal toxic concentration (MTC). Figure 3.2 displays the plasma concentration profile of different release dosage, forms after the oral administration of a drug. As can be seen from the figure, in case of traditional tablets or injections, the plasma drug concentration rises after each first dose then reduces until the next dose while with controlled drug delivery system; the plasma drug level remains constant between minimum and maximum for extended duration [2].

Fig. 3.2
figure 2

Plasma concentration versus time profile of different-release dosage forms. Reprinted with permission from [2] © 2009, American Chemical Society

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3.3 Significance of Nanoparticles in Drug Delivery

Nanoparticles (NPs) are potential candidates for controlled drug delivery systems due to their distinctive properties such as nanoscale size, varied surface chemistry, and unique pharmacokinetics. NPs have great surface to volume ratio therefore can readily cross the cell membranes and penetrate deeply into tissues [3]. Recently, the emergence of nanoparticles as drug delivery vehicles has fascinated significant interest for researchers in the field of biology and medicine. They allow for drug delivery with longer circulation half-lives, passive targeting, reduced side effects, and enhanced permeability and retention (EPR) effect. The most important advantage of using NPs as drug carriers is their ability to enhance aqueous solubility of hydrophobic drugs which in turn improve drug systemic circulation and eradicates fast renal excretion of drugs [4]. Among the different carriers for drug delivery, biodegradable nanoparticles can offer many benefits such as improved encapsulation, increased bioavailability, controlled and targeted drug release with minimal toxicity.

NPs exhibit greater accumulation at disease tissues than normal ones due to the EPR effect (passive targeting) [5]. Attempts were also done for the modification of biological species such as DNA, peptides, antibodies, proteins and aptamers (active targeting) in order to bind with targetable receptors present on the target cell surface [6]. Such an active targeting strategy can enhance therapeutic efficacy of a drug by facilitating cellular uptake and intracellular retention of the drug carriers [7]. The emergence of environmentally responsive NPs further improved NP therapeutic efficacy. These NP formulations respond to physiochemical changes within the microenvironments of organs, tissues, and cell organelles and release the drugs at target site [8]. Investigations are also going on different targeting strategies which deliver multiple therapeutic agents with single nanocarrier (Table 3.1).

Table 3.1 Advantages and limitations of nanoparticulate drug delivery systems
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3.4 Nanoparticle-Based Drug Delivery Platforms

Literature is enriched with a number of drug carriers for controlled drug release including liposomes, magnetic nanoparticles, dendrimers, polymer carriers, silica and gold nanoparticles, polymeric micelles and hydrogel nanoparticles.

3.4.1 Liposomes

The liposomes since their discovery have been of huge interest to scientists in the field of cosmetics, biology, and medicine [9]. Liposomes are considered as most frequently studied drug carriers owing to their unique properties such as composition, morphology, biodegradability, and simple method of preparation [10]. They are microscopic vesicles consists of an aqueous comportment enclosed by a hydrophobic lipid bilayer. Liposomes are amphipathic molecules comprise of hydrophobic tail and a hydrophilic head; therefore, they can trap both lipophilic and hydrophilic drugs. The therapeutic efficacy of hydrophilic small molecule drugs is limited because of their poor intracellular absorption. Such a limitation could be potentially overcome by means of colloidal drug delivery system [11]. Although liposomes are widely used as carriers of hydrophilic small drugs, their short blood circulation time and low stability can limit their therapeutic efficacy. Several approaches have been developed to overcome this drawback including coating liposomes with polyethylene glycol or chitin derivatives, incorporation of cholesterol into liposomes, freeze drying and polymerization.

PEG coating stabilizes liposomes against aggregation and fusion leading to enhancement in the liposomal circulation half-life and improvement in liposomal drug delivery in vivo. Many efforts have been made to design modified liposomal formulations with surface-attached ligands including antibodies, transferring, folates, and peptides to recognize and interact desired cells. A number of liposomal products are currently undergoing clinical trials as drug carriers and a few are already been approved by the Food and Drug Administration (FDA). For example, Doxil, the first FDA approved nano-drug is formulated in PEGylated nano liposome. Several PEGylated liposomal formulated drugs are also in clinical use e.g. Camptothecin and PEPO2 [12]. Apart from PEG conjugated lipids, a number of FDA approved conventional and cationic liposomal-based drugs (daunorubicin, amphotericin B, Cytarabine and Marqibo) are currently in the market, with many more in clinical trials. Despite of their wide spread applications, the clinical translation of liposome assisted drug delivery therapies not yet progressed.

3.4.2 Dendrimers

Dendrimers are well-defined, highly branched structures, comprise of a central core, repeated branches emerging from the core and surface functional groups. They display a wide variety of attributes including mono dispersity, low compressibility, high aqueous solubility, nanoscale dimensions and shape enable them highly promising candidates for drug delivery. A dendrimer drug delivery takes place by any one of the following methods. (i) Non covalent encapsulation of drugs: incorporation of drug molecules (physically entrapment) into the internal structure of dendrimer (ii) Covalent drug-dendrimer conjugates: the functional groups present on the surface of dendrimer can offer efficient conjugation to other functionalities on drug molecules. The interior core of dendrimer can accommodate hydrophobic drugs while exterior surface hold hydrophilic drugs that enhances the solubility of poorly soluble contents. Dendrimers have several advantages over liposome-based gene vectors, including high density of terminal groups, ease of surface modification and high permeability [13]. A number of dendritic derivatives including polyamidoamine (PAMAM), poly(etherhydroxylamine) (PEHAM), poly(propylene imine) (PPI), poly(esteramine) (PEA), poly-L-lysine, melamine, and polyglycerol reported as drug delivery carriers [14]. Among them, PAMAM is most extensively studied dendrimer for biomedical applications because its cationic nature helps in binding with DNA at physiological pH. PAMAM-drug conjugates also have the ability to bypass intestinal epithelial efflux pumps. Although dendrimers have wide variety of applications as drug and gene delivery vehicles, their multi step synthesis procedure limit their advancement of clinical trials.

3.4.3 Magnetic Nanoparticles

Recently, magnetic nanoparticles (MNPs) have been extensively used to develop magnetic targeted drug delivery system (MTDDS) where in magnetic field is used as an external stimulus to enhance local drug concentration at target sites. Owing to their super paramagnetic properties, ultrafine size and biocompatibility MNPs have gained significant interest in the field of biology and medicine. The release rate of active pharmaceutical ingredients from MNPs is usually regulated by external magnetic field, therefore drug delivered in a controllable way with less toxicity to healthy tissues. Another important benefit of MNPs as drug vehicles originates from their capacity to induce heat when subjected to alternating magnetic field (magnetic fluid hyperthermia). This allows to trigger the release of a loaded drug or to cause cell death by temperature-induced apoptosis [4]. Furthermore, MNPs induce a negative T2 contrast during magnetic resonance imaging enabling them to serve as efficient contrast agents. The other potential advantages of super-paramagnetic NPs over traditional cancer therapies are minimal invasiveness, accessibility of hidden tumors and reduced side effects.

MNP-drug conjugates coated with inorganic (silica, gold) or organic materials (phospholipids, polysaccharides, peptides, and polymers) exhibited greater therapeutic efficacy than the free drug [15]. For example, the conjugates of chitosan-modified magnetic nanoparticles and tissue plasminogen activator protein exhibited remarkable thrombolytic activity. Moreover, when this conjugate is used in magnetically targeted pyrolysis of in-stent thrombosis it did not induce hemorrhagic complications which are frequently observed with traditional thrombolytic therapy. MNPs embedded in polymer capsules can be used to enhance the permeability of microcapsules by applying external magnetic fields, e.g. ferromagnetic Au-coated cobalt NPs were incorporated into the polymer walls of microcapsules. Applying external magnetic fields to these conjugates disturb the capsule wall structures which in turn enhances the permeability to macromolecules. The limited clinical use of MNPs as drug carriers is mainly due to their tendency to aggregate into large clusters. This limitation can be overcome by combining MNPs with synthetic or biological polymers which could prevent aggregation.

3.4.4 Hydrogels

Hydrogels are three dimensional networks of polymer chains attracted tremendous attention in control drug delivery. The utility of hydrogels as drug carriers can be esteemed by their ability to absorb and retain large quantities of water and their swelling behavior [16]. However, they will not dissolve in aqueous environment due to their cross-linked networks. The advantageous characteristics which make them promising drug delivery candidates are flexibility, high water absorptivity, hydrophilicity, and biocompatibility. The drugs loaded in the porous structures of hydrogel matrix could be released in a controllable way over extended period of time. Recently, smart nanogels are particularly interesting in drug delivery owing to their responsiveness to external stimuli. Entrapment of different structures into hydrogels further improves their drug release patterns. For example, hydroxyethyl cellulose-based hydrogels entrapped with liposomes have been reported for efficient release of calcein. Despite these applications, difficulty in handling low mechanical strength, high cost and macroscopic dimensions of hydrogels limit their use for in vivo applications.

3.4.5 Polymeric Micelles

Self-assembly of amphiphilic block copolymers in aqueous medium resulted in the formation of polymeric micelles (PMs). They comprise of hydrophobic core which acts as a reservoir for lipophilic drugs and a hydrophilic shell provides stabilization in aqueous solution [17]. Polymeric micelle-based DDS have proven to be promising because of their following beneficial characteristics (i) solubilization of lipophilic moieties in hydrophobic core (ii) improved blood circulation time (iii) biocompatibility (iv) structural stability (v) low toxicity. The inner core of micelles can accommodate a large amount of hydrophilic drug molecules and the exterior shell serves as a barrier by preventing them dispersity aggregation [18]. Another significant advantage of PMs make them efficient drug carriers is their larger size which suppress or eliminate renal excretion. The drawbacks of using PMs as drug delivery vehicles are slow extravasation and difficulty in polymer synthesis.

A variety of drugs have been entrapped in micellar DDS in order to enhance the therapeutic efficacy e.g. DOX encapsulated monomethoxy PEG (mPEG)-b-P(CL) micelles were studied for anti-tumor activity against B16-F10 melanoma cells. This encapsulation allows the cellular uptake of drug which in turn enhances the DOX cytotoxicity. Some PM formulated drugs are currently in clinical trials e.g. Genexol-PM conjugates developed against pancreatic, ovarian, and gastric cancer. The poor aqueous solubility of Currculin (Cur) limited its clinical applicability. This limitation was overcome by Cur-loaded biodegradable mPEG-b-P(LA) micelles exhibiting remarkable antiangiogenic and antitumor activities over free Cur. It is well known that folic acid (FA) is an important targeting moiety for DDS as folate receptor (FR) is present on the surface of most of human cancer cells. Recently, PM-drug conjugates developed by conjugating PEG-bP(LGA)-DOX and FA-PEG-b-P(LGA) diblock copolymers and studied against antitumor activity. Interestingly, FA-targeted DOX-containing micelles were efficiently accumulated at target site and showed greater activity than free DOX or nontargeted PEG-b-P (LGA)-DOX micelle. The emergence of smart PMs which responds to the environmental signals and external stimulations further extend their potential as promising DDS.

3.4.6 Gold Nanoparticles

Gold nanoparticles (AuNPs) are ideal candidates to be used in DDS since they exhibited non toxicity and non-immunogenicity [19]. The use of gold NPs as drug delivery vehicles has several advantages including inertness, greater surface area, simple procedures for synthesis, structural stability and increased half-life of the drugs. In addition to that, they can be functionalized with different targeting moieties in that they offer useful complement to platinum-based drugs. Since AuNPs exhibit strong affinity to functional groups such as thiols, carboxylates, amines and phosphates, they can be readily conjugated with wide variety of molecules like amino acids, proteins, polymers, and drugs. As it is well known, gold is highly resistant to bacteria, AuNPs can be used to prevent the bacterial growth in infections. Furthermore, AuNPs have been used extensively in the diagnosis of cancer due to their optical and photophysical properties.

Most of the human cancer cells express a protein epidermal growth factor receptor (EGFR) on their surface. Since gold is a good heat conductor, radio frequency is used to heat the AuNPs which in turn heat cancer cells that can led to destroy the malignant tumors. Researchers conjugate AuNPs to an antibody for EGFR (Anti-EGFR) enable them to accumulate to cancer cells. A number of studies have been performed on the AuNP-based drug delivery systems. PEGylated AuNPs were conjugated with TNF-α, in order to enhance the tumor damage and reduce the systemic toxicity of TNF-α. Interestingly, this nanoparticle conjugate exhibited greater therapeutic efficiency than free TNF-α. Recently, Sershen’s group focused on the development of photothermally-modulated drug delivery system from the composites of hydrogel and gold nanoshells. On irradiation at 1064 nm, these conjugates release active ingredients in controlled fashion [20]. The drawbacks of AuNP-based drug delivery strategies are their acute or chronic toxicity, exhibiting difficulties in vivo kinetics, biocompatibility and display weak optical signals compared to quantum dots.

3.5 Applications of Nanoparticles in Drug Delivery

Destroying biological pathogens is easy. The point is how to destroy them while sparing the host. This is especially obvious when dealing with cancer. Despite recent progresses in the diagnosis and treatment, lung cancer still remains the leading cause of death due to tumor where worldwide gastric cancer (GC) is the fourth most common malignant disease and the second leading cause of cancer mortality worldwide [21,22,23,24]. To critically evaluate treatment wait times in CRC (colorectal cancer) patients and identify clinical and systemic barriers to treatment even the complexities of cancer, chemotherapy frequently fails for many unknown reasons. Recent technological advances, including single cell genomic technologies, anti-mitotic drugs target the reorganization of microtubules, essential for proper cell division and proliferation. The epigenetic machineries have proven roles in a wide variety of cancers [25]. For patients with metastatic or recurrent GC, the evidence supports the use of chemotherapy to prolong survival and maintain quality of life. Advances in the treatment of ovarian cancer over the past decade, have led to emphasize the concept of managing ovarian cancer as a chronic disease [26].

A variety of polymeric nanoparticles, including polymer conjugate complexes [27, 28], nanospheres [29,30,31], micelles [32,33,34], and dendrimers [35,36,37] have been developed to aid in the delivery of drugs to cancerous sites and have shown great efficacy against various types of cancers. Conjugation of drug molecules to the polymer backbone allows for precise drug loading and control over release kinetics [38]. Self-assembled nanospheres, micelles, and dendrimers loaded with therapeutic agents offer sustained and controlled release through surface or bulk erosion, drug diffusion through the polymer matrix, or environmental activation or stimulation [39]. By combining an imaging agent along with the encapsulated drug within a polymeric nano-particle, researchers have been able to achieve analysis of drug distribution and release at the target site in real time. The live evaluation of drug distribution provides assistance in predicting drug response and can better facilitate treatment regimens to be specifically tailored for each individual.

A recent study of polymer nanoparticles suggested the targeted delivery of drug to cancerous liver cells. The polymer nanoparticles were synthesized using D-α-tocopherol polyethylene glycol 1000 succinate and poly(lactide) and modified with polydopamine. Galactosamine was conjugated on prepared nanoparticles to enhance the delivery of docetaxel (DTX) via ligand mediated endocytosis [40]. The study of these modified functional polymer nanoparticles in vitro showed that coumarin 6-loaded nanoparticles have the highest cellular uptake efficiency in liver cancer cell line HepG2 than other tested nanoparticles. The in vivo biodistribution experiment the modified functional polymer nanoparticles targeted specifically to the tumor cells and on injecting DTX loaded polymer nanoparticles reduced the size of tumor significantly on hepatoma bearing nude mice. The authors investigated in vitro cellular uptake and cytotoxicity assay, found that Gal-pD-TPGS-PLA/NPs approach HepG2 cells via ASGP receptor mediated recognition, and significantly inhibits cell proliferation. Furthermore, DTX-loaded Gal-pD-TPGS-PLA/NPs reduced tumor size more evidently in vivo than Taxotere, DTX-loaded TPGS-PLA/NPs or pD-TPGS-PLA/NPs, or saline. Therefore, the prepared Gal-pD-TPGS-PLA/NPs could potentially qualify as a drug delivery system targeting liver cancers or other liver diseases.

Chitosan modified single walled carbon nanotubes (SWCNTs) were constructed for controllable release of doxorubicin, an anti-cancer agent [41]. For easy transmission of drug, the delivery vehicle, chitosan modified SWCNTs were cut and purified before use. The use of chitosan in the preparation of drug delivery vehicle makes the delivery vehicle more soluble and biocompatibility of single walled carbon nanotubes and increased surface activity to bind targeted molecule. The researchers found that the biocompatibility of DOX/FA/CHI/SWCNTs was greater than bare DOX. HCC cell line (SMMC-7721) cells were exposed to FA/CHI/SWCNTs for an hour and then cultured in fresh media for additional 72 h. The viability was maintained at 86% which itself confirms the biocompatibility of the delivery vehicle. According to author’s expectations, the DOX/FA/CHI/SWCNTs induced serious cytotoxicity at even much lower dose than bare DOX. The synthesized formulation also possessed low systematic toxicity as after intravenous injection of DOX/FA/CHI/SWCNTs increased the weight of mice while after injecting bare DOX the weight decreased significantly. This observation was in consistent with the toxicity of bare DOX and proves that DOX/FA/CHI/SWCNTs have lesser toxicity compare with bare DOX. The platelet level and aminotransferase were increased due to toxicity of bare DOX [42]. However, the platelet level and aminotransferase levels were much lower than bare DOX, indicating less toxicity and low damage to liver. Hence, the DOX-SWCNTs conjugate can easily bind with the tumor sites while bare DOX is nonspecific and DOX can easily enter into the cell due to cell membrane penetration ability of SWCNTs [43, 44].

A recent study was done to develop paclitaxel loaded self-assembled nanoparticles which were prepared by using the block copolymers synthesized by ß-poly(lactide) and poly(γ-glutamic acid) [45]. The prepared composite nanoparticles were conjugated by galactosamine. The galactosamine conjugated nanoparticles (Gal-P/Nps) were compared with available paclitaxel formulation drug in the market (Phyxol®). The release profile of paclitaxel drug was almost same in the case of both P/NPs and Gal-P/NPs and it was almost a burst (Fig. 3.3a). The cell viability of Gal-P/NPs was comparable with the paclitaxel drug while the P/NPs showed very less cell viability (Fig. 3.3b). The author inspected the growth of tumor for 20 days in nude mice injected with PBS (control) and different paclitaxel formulations (Fig. 3.4). It was observed that the size of tumor increased significantly, which means control have no effect on tumor growth prevention. However, the other formulations inhibited the growth of tumor as compared to control. The drug loaded Gal-P/NPs group showed most significant inhibition of tumor growth among all the groups tested. The Gal-P/NPs targeted actively to the tumor sites and subsequently released the encapsulated paclitaxel which resulted in the inhibition of tumor growth. All the groups have shown the weight loss of nude mice except Gal-P/NPs group because all other formulation affected tumor cells as well as normal cells. The Gal-P/NPs formulation can be used in hepatoma tumor via the ASGP receptor-mediated recognition and may be used in liver cancer.

Fig. 3.3
figure 3

a Release profiles of paclitaxel from the P/NPs or Gal-P/NPs; b viability of HepG2 cells treated with distinct paclitaxel formulations with varying paclitaxel concentrations. Phyxol ® cells treated with a clinically available paclitaxel formulation; P/NPs cells treated with the paclitaxel-loaded NPs without galactosamine conjugation; and Gal-P/NPs cells treated with the paclitaxel-loaded NPs with galactosamine conjugation. Reprinted with permission from [45] © 2006, Elsevier

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Fig. 3.4
figure 4

Changes in the tumor volume of the hepatoma-tumor-bearing nude mice injected with distinct paclitaxel formulations. PBS mice injected with PBS; Phyxol ® mice injected with a clinically available paclitaxel formulation; P/NPs mice injected with the paclitaxel-loaded NPs without galactosamine conjugation; and Gal-P/NPs mice injected with the paclitaxel-loaded NPs with galactosamine conjugation. Reprinted with permission from [45] © 2006, Elsevier

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Lung cancer is also a major concern today and there are several bacterial species which are associated with it like Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, and Haemophilus influenza etc. However, the available drugs in the market have many side effects to the healthy cells. In recent years, smart lipid nanoparticles have been developed as a potential system for lung delivery [46,47,48] due to its nontoxic, biodegradable, small size and physiochemical properties [49]. Some researchers have selected levofloxacin as the antibiotic mode for encapsulation due to its strong toxicity towards P. aeruginosa [50]. Although, levofloxacin is safe antibiotic among quinoline drugs, its prolong use or higher consumption may result in serious nephrotoxicity after oral dose [51]. The lipid myristyl myristate was chosen by the researchers to encapsulate levofloxacin. The properties of smart lipid nanoparticles can be improved by incorporating them into new generation of nanoparticles called nanostructured lipid carriers [52]. It has been shown that lipid nanoparticles had controlled release for about 48 h (Fig. 3.5) which help to reduce the high concentration of drug in the body and beneficial to the patient’s comfort. The smart feature of these nanoparticles is the dual capability to deliver an antibiotic and a hydrolytic enzyme of DNA to reduce the biofilm formation of the bacteria and increase antimicrobial activity which improves the fight against cystic fibrosis lung infection.

Fig. 3.5
figure 5

Release profiles of Levofloxacin from smart lipid nanoparticles (SLN) and nanostructured lipid carrier (NLC) formulation (4.0 µg/ml of initial levofloxacin). Errors: SD, n = 3. Reprinted with permission from [50] © 2016, Elsevier

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3.6 Conclusions

The drug delivery to the specific target cell or tumor is an instantly growing field among the researchers. The development of new drugs is a time taking and very complicated process while improving the performance of currently available drugs is a comparable easy task. Therefore, researchers are preferring targeted controlled drug delivery system to enhance the activity of available drug. The implication of nanoparticles as a drug delivery vehicle further improved the performance of drugs by utilizing the exceptional properties of nanoparticles like biocompatibility, ability to encapsulate, aqueous stability, biodegradability, functionalization. Due to small dimensions, nanoparticulates are able to cross the blood-brain-barrier and operate on cellular level. These properties of nanoparticles are the leading attraction among scientists which are interested in the fabrication of novel multifunctional nanoparticles that can target tumor cells with more precision and specificity. Despite of having several advantages, nanoparticles formulations have some disadvantages too. The large number of functional groups on the surface of nanoparticles attach with the carrier only in a stoichiometric ratio. The oxidative stress and inflammation in different cell types have been often reported as toxic mechanisms of various types of nanoparticles. The sub-nanometer scale particles may remain in the cells and may induct chronic inflammatory response and fibrosis of tissues. The nano drug delivery carrier should also be tested for safety in drug delivery and other biomedical applications. The drug carrier and its degraded products should ensure the safety of healthy cells. Therefore, a large amount of exploration should be done on the pharmacodynamics, metabolism in vivo, and nanocarriers are the future of medicine. Extensive research is needed to make the switching of these nano drug carriers from laboratory to market.