A drug delivery system can be defined as the mechanism for the introduction of drug and other therapeutic agents into the body for treating any disease. An ideal drug delivery system possesses two elements: (1) the ability to target -to ensure high efficiency and reduce the side effects, (2) controlled drug release & (3) prevention of side effects [8]. Using nanomaterials for drug delivery NDD (nanoparticle drug delivery) has the following advantages:

reduced drug toxicity

better penetration of the particles

different delivery routes

minimizes the irritant reactions

improved bio-availability and increased circulation time

controlled drug release and targeting

It is one of the “Green Technology” methods as the focus is on minimizing the hazard & side effects and maximizing the efficiency of any chemical (drug) of choice and replacing the existing products with new nanoparticles that are friendly throughout their lifecycle[8],[7].

QUANTUM DOTS FOR NDDS:

NDDS means Nanoparticle Drug Delivery System. A system with high sensitivity, large resolution, and low cost is needed for the maintenance of drug delivery i.e. to check the nanocarrier distribution, drug release and degradation inside the body. Quantum Dots are highly suitable for such systems.[1] The important characteristics of Quantum dots which make them suitable for drug delivery systems are: small size, versatility of surface chemistry to incorporate various drugs, unique optical properties for real time monitoring of drug transport and release both at systemic and cellular levels. These Quantum Dots can be used as carriers by integrating with many drugs and also used as tags for other drug carriers. [6]

WHY QUANTUM DOTS???

One of the important reasons why Quantum Dots are preferred is that it can be used for the traceable drug delivery as it has the potential to elucidate the pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body) of drug when it is introduced into our body [6]. Using QDs will be a combination of unique physical, chemical, and optical properties which helps to study the interactions of these nanocarriers with biological systems through real-time monitoring and calculating the biodistribution of nanoparticle, drug release, intracellular uptake and degradation [5]. Comparing to the conventional imaging techniques like MRI and PET, the optical imaging using Quantum Dots is highly sensitive with high resolution and at very cheap cost which will automatically lead to the reduction of time involved in the development of new drug and many discoveries in the field [6].

ADVANTAGES OF USING QDs

Optical imaging with high resolution, high sensitivity, multiplexing, and low cost

Small size which leads to less amount of drug usage and low drug toxicity

Versatile surface chemistry,

Improved bioavailability and delivery of drug in a controlled and sustained manner

Decreased incidence of side effects and improve patient compliance

Comparing other conventional probes, QDs are more resistant which allows tracking cell processes for longer periods of time and which will lead to discovery of new molecular interactions

Quantum dots have size dependant emission which can be modified according to our requirement (from UV to IR range)

Fluorescence is seen for longer time when compared to conventional dyes.

The extremely small size gives them great flexibility by allowing them using different delivery routes eg. they can be injected as liquid mixtures, fabrics, and polymer.[7]

PROPERTIES OF QDs

Some of the properties of Quantum Dots that are used to examine nanocarrier behavior in biological systems are: ([2], [5],[7])

Small size: size maybe around 2-10 nm in diameter that enables tagging of drug/carriers. Single or multi-component systems can be labeled for tracing and monitoring

Surface chemistry: compatibility with various drug carriers integrating a wide range of nanoparticle drug carrier system.

Emission profile: identifying quantum dots by its sharp narrow emission peak allows simultaneous observation of multiple nanocarriers within a same system.

High brightness: detection of QDs inside body facilitates the tracing of nanocarriers in vivo.

High photostability: QDs are more resistant to photobleaching that enables long term real time tracking.

QUANTUM DOTS AS NANOCARRIERS

Quantum Dots are considered as carriers and the therapeutic drug molecules are directly linked to them to be delivered to the target sites. Here it serves as both vehicle carrying the drug and tracing probe used for the real time monitoring. In drug delivery, size of the Quantum Dots is considered as a very important parameter. The size of QDs varies from 2 – 10 nm, and it increases to 5 – 20 nm in diameter after drug encapsulation. It should be noted that QDs of size smaller than 5 nm are removed in the process of renal filtration and those particles bigger is size have problems in penetrating through the tissues and many bigger particles are wiped out before they could reach their destination.

Another important characteristics of QDs to be considered for drug delivery is the ratio of surface-to-volume. If this ratio is high then multiple carriers can be linked on single QDs without changing the average diameter of the nanocarrier system. Thus the ratio of surface-to-volume should be high.

Fig.1 A Multifunctional Quantum Dot coated with Amphiphillic Polymer [6]

The above figure illustrates that QD acts as core structural hydrophobic scaffold and the amphiphillic polymer is coated outside the core. The drug molecules which are hydrophobic in nature are embedded between the core and the polymer coating. And those hydrophilic therapeutic molecules can be incorporated on the amphiphillic coating. Multiple layers of ligands can be linked in subsequent layers not directly linked to the QD core but to the previous layers of coating and is controlled by them. These nanocarriers also protect the therapeutic molecule or proteins used from the body’s own immune system defense mechanism by encapsulating them within themselves. [6]

Yamomoto et al did research on using quantum dots to treat stroke in and reported that the nanocarriers “QD – captopril conjugates” were capable of lowering blood pressure in rats. But it was not known whether the therapeutic effect of lowering pressure was due to the conjugate or the detached drug from the quantum dots. [6]. Not only drugs, other therapeutic molecules like small interfering RNA, oligodeoxynucleotide and biomolecules e.g. antibodies, peptides can also be incorporated into the nanocarriers. siRNA delivery using quantum dots was reported by Bhatia et al. siRNA moleculeas were successfully delivered using targeted nanocarriers because of the size similarity between QDs and siRNA. Whereas larger molecules like plasmid will require many QDs for successful delivery. [6]

Mn-doped ZnS Qds encapsulated with glycopolypeptide were fabricated for the drug delivery. Characterization and in vitro studies were done to prove the low cytotoxicity of the nanocarriers and it was good effort for the targeted drug delivery [4].

QUANTUM DOTS AS TAGS FOR OTHER DRUG CARRIERS

Due to the unique properties of Quantum Dots, they are used as tags to label other drug carriers and are used as traceable drug delivery. The high photostability helps in the real time tracking of the nanocarrier inside the body. Therefore strong fluorescence signal indicates higher uptake of drug by the cells. The wavelength of the emitted signal depends on the size of the Quntum Dots used. Thus it is very specific to the QDs and thereby simultaneous nanocarriers can be used and the signals can be easily identified.

Chen et al. reported about their work of siRNA delivery with QD conjugated with Lipofectamine. The results showed that fluorescence intensity of QD is proportional to the degree of silencing i.e. if lipoplex uptake is more than the fluorescence will be stronger. [6] Another work done by Zhang et al. reported the synthesis of QD-chitosan conjugate nanobeads for the delivery of siRNA. It was successfully traced because of the conjugation with QDs. [6] Amphipol nanocpmplex were prepared for the real time imaging of siRNA by Lifeng et al. it was delivered intracellularly and imaged in a real time pattern. [12]

SYNTHESIS AND CHARACTERIZATION

There are many ways of preparing Quantum Dots. Some of the noted process of fabricating QDs are Lithography, Colloidal synthesis, Epitaxial methods, some chemical methods [2],[10].

Generally NDDS is prepared in the following steps:

Nowadays many non-toxic semiconductor QDs are used for the drug delivery. Consider for example ZnO. It is a non-toxic semiconductor when compared to other Quantum Dots such as CdS, CdTe. These QDs can be combined with biocompatible and biodegradable polymer to increase the stability and non-immunogenicity of the nanocarriers. It also shields the nanocarriers from the interference of other interacting molecules inside biological environment. Chitosan is a natural copolymer which on encapsulation enhances the quantum dots properties like solubility in water, metal chelation and easy processing and biocompatibility [3].

Characterization studies like TEM, UV-VIS, PL spectroscopy, FTIR, Drug release response test are done after the synthesis. TEM is used to find out the size range of the fabricated QD. PL and PLE spectra give information about the emission spectra. FTIR confirms the incorporation of the drug into the QD and Drug release response test gives the amount of drug released and tells about the type of drug delivery. [10], [3].

CONCLUSION:

Quantum Dots will be the future of drug delivery systems if the only drawback has been eliminated. The only disadvantage in using Quantum Dots is their “long term toxicity”. This can be overcome by replacing the core of the QD with biocompatible agents like gold or magnetic nanoparticles which offers a unique combination of therapy like magnetofection and photothermal treatment. Recent studies show that quantum dots to be safe on primates [9]. Quantum Dots will be a powerful tool to diagnose and treat cancer [11]. Thus quantum dots will become the new era of drug delivery.