A Review on Nanoparticles in Targeted Drug Delivery System
Sriharitha1* and Preethi J2
1ASN College of Pharmacy, Tenali, AP, India
2Acharya Nagarjuna University, Guntur, Andhra Pradesh, India
- *Corresponding Author:
- Sriharitha M
Pharmacy, ASN College of Pharmacy
Tenali, AP, India
E-mail: [email protected]
Received Date: August 26, 2016; Accepted Date: September 16, 2016; Published Date: September 21, 2016
Visit for more related articles at Research & Reviews: Journal of Material Sciences
To improve the pharmacokinetic and pharmacodynamics activity of the drug medication system like nanoparticles has made a break through by means of physical application. By means of targeted drug delivery system the targeted drug delivery will be achieved quickly. To maintain a controlled and sustain the rate of drug exposure on the site of action nanoparticles are used. That’s the reason why the nanotechnology became as the most advanced in the field of medicine by maintaining the therapeutic benefits. Scientists performing many trails in the field of nanotechnology to reformulate the existing essential drugs to minimize the adverse effects and to increase the therapeutic effects. Some of the innovative concepts like nano-delivery, sustain release, etc have already became a breakthrough. The main concept of the paper is to elevate the basic concepts to use in the field of nanoparticles preparation and advantages.
Nanoparticles, Site specificity, Targeted drug delivery system
Nanotechnology is the science which deals with small; the very small particles. At the NANO size, atoms and molecules exhibits surprising and interesting outcomes by working differently which results in various scientists to concentrate on these to use in many fields like medical, Pharma, engineering etc. [1-3]. Delivering therapeutic compound to the target site is a noteworthy issue in treatment of many diseases. Many conventional dosage forms failed in vain in delivering the drug at specific site of action due to its limited effectiveness, poor bio-distribution, and lack of selectivity. These limitations and draw backs can be overcome by novel drug delivery systems . Through novel drug delivery systems various drugs can be delivered to the desired (specific) sites showing its pharmacological activity by minimizing side effects. More over novel drug delivery systems protects drug from rapid degradation and maintains drug concentration at specific sites or in target tissues hence lower doses of drug are required [5-9].
Nanostructures have the ability to cross the cell and tissue barriers as its particle size is very small which makes them widely applicable in biomedical sciences .
The Novel drug delivery system (Nanoparticles) is used to deliver drugs through oral, nasal, parenteral, intra-ocular etc.
Through nanoparticles particle size can be easily altered resulting in attaining both active and passive drug targeting after parenteral administration became the most advantageous in the treatment of many chronic diseases [11,12].
Nanoparticles have the ability to control and sustain the drug before reaching the specific site of action and protects drug from rapid degradation and maintains drug concentration at specific sites or in target tissues hence with lower doses of drug shows high therapeutic efficacy and reduced side-effects.
One more important advantage of nanoparticles is high levels of drug can be incorporated without any chemical reaction resulting in the preservation of pharmacological activity of the drug [13-15].
Used in targeted drug delivery (therapy) to brain and cancer therapy [16-18],
Drug and gene delivery,
Bio detection of pathogens,
Detection of proteins,
Probing of DNA structure,
Destruction of tumours through heating process (hyperthermia),
Separation and purification of biological molecules and cells,
MRI contrast enhancement,
In spite of many advantages nanoparticles have some limitations which make researches to work more on it to attain even more best therapeutic efficacy with lesser side effects .
Aggregation of particles may takes place due to its altered physical properties especially in liquid and dry forms because of its smaller particle size and larger surface area.
Due to its particle size (smaller) and larger surface area nanoparticles are very reactive in the cellular environment [20,21].
Drug loading and burst release is limited because of its smaller particle size.
Evalutaion of Nanoparticles
Zeta potential is the potential difference existing between the surface of a solid particle immersed in a conducting liquid (e.g. water) and the bulk of the liquid . The surface charge of the nanoparticles is usually measured by Zeta potential. Particles with above ± 30 Mv zeta potential were stable in suspension form as their surface charge prevents aggregation of particles [23-27].
Particle shape of the nano suspensions is determined by scanning electron microscopy (SEM) [28,29]. Inorder to form the solid particles these Nano suspensions were subjected to lyophilisation. Thus formed solid particles are coated with platinum alloy using a sputter coater .
Particle size and its distribution is important characteristics in nanoparticles as they plays a major role in distribution, pharmacological activity, toxicity and targeting to specific sites (site specificity) [31-33]. On the other hand drug loading capacity, percentage of drug release and stability of the nanoparticles also depends on its particle size and distribution . Advanced methods to determine the particle size of nanoparticles is by photon-correlation spectroscopy or dynamic light scattering. The results thus obtained were examined by scanning electron microscopy (SEM) .
Drug Entrapment Efficiency
Ultracentrifuge the nanoparticles at 10,000 rpm for 30 min and maintain temperature at 50C in order to separate them from aqueous medium . To remove the unentrapped drug molecules the supernatant was decanted and then it is dispersed into phosphate buffer saline pH 7.4 [37,38]. Repeat twice the procedure for complete removal of unentrapped drug molecules. The difference between the amount of drug used to prepare nanoparticles and amount of drug present in the aqueous medium gives the amount of entrapped drug into the nanoparticles [39-43].
Drug Entrapment efficiency (%)=Amount of drug released from nanoparticles after centrifugation/Total amount of drug used to prepare nanoparticles.
Preparation of Nanoparticles
Nanoparticles were prepared from a wide variety of materials and polymers. Materials like polysaccharides, proteins whereas polymers like synthetic polymers. Selection of the matrix materials should be done based on many factors like nanoparticle size, properties of drug like solubility of the drug in aqueous medium and drug stability, permeability and charge of the drug molecules, extent of biodegradability, biocompatibility and toxicity and drug release profile .
Preparation of nanoparticles has been done by three methods
This method is the most common method to prepare the bio degradable nanoparticles from poly lactic acid, poly D,Lglycolide, poly D,L-lactide-coglycolide by means of two methods,
a) Solvent evaporation method: the polymer is dissolved in the organic solvents like dichloromethane, chloroform or ethyl acetate which helps in dissolving the hydrophobic drug, and then by using surfactants or emulsifiers the drug solution and polymer solution are mixed to form an oil in water emulsion [45-47]. After the formation of a stable emulsion the solution is then evaporated by reducing pressure. Particle size was found to be influenced by the polymer concentration, Polymer type, concentrations of stabilizer and homogenizer speed. In order to produce small particle size, often a high-speed homogenization or ultra-sonication may be employed [48-50].
b) Spontaneous emulsification: this is the modified method of Solvent evaporation, where water miscible solvent along with the water immiscible organic solvent is used as an oil phase [51-53]. Due to spontaneous diffusion interfacial turbulence is created between the two phases creating the small particles.
In this method the monomers are polymerized to create the nanoparticles in an aqueous solution. The drug particles are then introduced to the aqueous solution then the suspension is purified to remove the impurities like surfactants and stabilizers which are used earlier [54-58]. By using ultracentrifugation or re-suspending the particles in the isotonic surfactant-free medium the nanoparticles are collected [59,60]
Ionic gelation method or coacervation technique: Ionic gelation method is carried out using the biodegradable hydrophilic polymers such as chitosan, gelatin and sodium alginate by means of ionic gelation [61-63]. In the process, the hydrophilic chitosan nanoparticles are ionized by ionic gelation by positively charged amino groups of chitosan reacts with negative charged tripolyphosphate to form the nanoparticles by coacervation [64,65].
Novel drug delivery systems plays a major role in site specific drug delivery (Targeted drug delivery) compared to conventional dosage forms due to its advantages in site specificity and stability. The main aim in designing Novel drug delivery system (nanoparticles) is to alter or modify particle size of the drug, its surface properties thus reaching pharmacologically active drug molecules to its specific site action with minimal dose and reduced dosing frequency. Nanoparticles became very popular drug delivery system as it increases the stability and protects drug molecules from rapid degradation.
- Divya L and Vijay KM. Preparation and Applications of Chitosan Nanoparticles: A Brief Review. Material Science. 2016.
- Sougata G, et al. Gloriosa superba Mediated Synthesis of Silver and Gold Nanoparticles for Anticancer Applications. J Nanomed Nanotechnol. 2016;7:390.
- Rajesh A. Applications of Upconversion Nanoparticles in Nanomedicine. J Nanomed Nanotechnol. 2016;7:e141.
- Kshitij RM and Dipak KS. SLNs can Serve as the New Brachytherapy Seed: Determining Influence of Surfactants on Particle Size of Solid Lipid Microparticles and Development of Hydrophobised Copper Nanoparticles for Potential Insertion. J Chem Eng Process Technol. 2016;7:302.
- Khalid A and Tawfik AS. Gold and Silver Nanoparticles: Synthesis Methods, Characterization Routes and Applications towards Drugs. J Environ Anal Toxicol. 2016;6:384.
- Heidari A. Pharmacogenomics and Pharmacoproteomics Studies of Phosphodiesterase-5 (PDE5) Inhibitors and Paclitaxel Albumin-Stabilized Nanoparticles as Sandwiched Anti-Cancer Nano Drugs between Two DNA/RNA Molecules of Human Cancer Cells. J Pharmacogenomics Pharmacoproteomics. 2016;7:2.
- Sreelakshmy V, et al. Green Synthesis of Silver Nanoparticles from Glycyrrhiza glabra Root Extract for the Treatment of Gastric Ulcer. J Dev Drugs. 2016.
- Liron LI, et al. Ultrasound-Mediated Surface Engineering of Theranostic Magnetic Nanoparticles: An Effective One-Pot Functionalization Process Using Mixed Polymers for siRNA Delivery. J Nanomed Nanotechnol. 2016;7:385.
- Yadav JP, et al. Characterization and Antibacterial Activity of Synthesized Silver and Iron Nanoparticles using Aloe vera. J Nanomed Nanotechnol. 2016;7:384.
- Dou Z, et al. Effect of Al2O3 Nanoparticles Doping on the Microwave Dielectric Properties of CTLA Ceramics. J Material Sci Eng. 2016;5:256.
- Vanitha KG, et al. Synthesis and Characterization of Pectin Functionalized Bimetallic Silver/ Gold Nanoparticles for Photodynamic Applications. J Phys Chem Biophys. 2016;6:221.
- Heydrnejad MS and Samani RJ. Sex Differential Influence of Acute Orally-administered Silver nanoparticles (Ag-NPs) on Some Biochemical Parameters in Kidney of Mice Mus musculus. J Nanomed Nanotechnol. 2016;7:382.
- Jibowu T. The Formation of Doxorubicin Loaded Targeted Nanoparticles using Nanoprecipitation, Double Emulsion and Single Emulsion for Cancer Treatment. J Nanomed Nanotechnol. 2016;7:379.
- Heidari A. Ab Initio and Density Functional Theory (DFT) Studies of Dynamic NMR Shielding Tensors and Vibrational Frequencies of DNA/RNA and Cadmium Oxide (CdO) Nanoparticles Complexes in Human Cancer Cells. J Nanomedine Biotherapeutic Discov. 2016.
- Alaa El-Din HS. Evaluation of Apoptotic Cell Death and Genotoxicty Following Exposure to Silver Nanoparticles in African Catfish (Clarias gariepinus). Toxicol open access. 2016;2:108.
- Chan Li, et al. Development and Validation of a Method for Determination of Encapsulation Efficiency of CPT-11/DSPE-mPEG2000 Nanoparticles. Med chem (Los Angeles). 2016;6:345.
- Heidari A. Pharmaceutical and Analytical Chemistry Study of Cadmium Oxide (CdO) Nanoparticles Synthesis Methods and Properties as Anti-Cancer Drug and its Effect on Human Cancer Cells. Pharm Anal Chem. 2016;2:113.
- Heidari A. A Chemotherapeutic and Biospectroscopic Investigation of the Interaction of Double Standard DNA/RNA Binding Molecules with Cadmium Oxide (CdO) and Rhodium (III) Oxide (Rh2O3) Nanoparticles as Anti Cancer Drugs for Cancer Cells Treatment. Chemotherapy (Los Angel). 2016;5:e129.
- Brajesh K, et al. Aqueous Phase Lavender Leaf Mediated Green Synthesis of Gold Nanoparticles and Evaluation of its Antioxidant Activity. Biol Med (Aligarh). 2016;8:290.
- Carina S and Luis C. Optimized Synthesis of Multicomponent Nanoparticles for Removing Heavy Metals from Artificial Mine Tailings. Biol Med (Aligarh). 2016;8:288.
- Heidari A. Novel and Stable Modifications of Intelligent Cadmium Oxide (CdO) Nanoparticles as Anti-Cancer Drug in Formation of Nucleic Acids Complexes for Human Cancer Cells Treatment. Biochem Pharmacol (Los Angel). 2016;5:207.
- Julia S, et al. Flurbiprofen-loaded Nanoparticles Can Cross a Primary Porcine In vitro Blood-brain Barrier Model to Reduce Amyloid-ÃÅ½Â²42 Burden. J Nanomedine Biotherapeutic Discov. 2016.
- Moradpour M, et al. Establishment of in vitro Culture of Rubber (Hevea brasiliensis) from Field-derived Explants: Effective Role of Silver Nanoparticles in Reducing Contamination and Browning. J Nanomed Nanotechnol. 2016;7:375.
- Sanjib B, et al. Modulating the Glucose Transport by Engineering Gold Nanoparticles. J Nanomedine Biotherapeutic Discov. 2016.
- Julio CF, et al. Acellular Human Amniotic Membrane Scaffold Loaded with Nanoparticles Containing 15d-PGJ2: A New System Local Anti-Inflammatory Treatment of Eye Diseases. J Clin Exp Ophthalmol. 2016;7:537.
- Mohammed G, et al. Study of the Cytotoxicity Effect of Doxorubicin-loaded/Folic acid-Targeted Super Paramagnetic Iron Oxide Nanoparticles on AGS Cancer Cell Line. J Nanomed Nanotechnol. 2016;7:368.
- Pereira da SS, et al. Iron Oxide Nanoparticles Coated with Polymer Derived from Epoxidized Oleic Acid and Cis-1,2-Cyclohexanedicarboxylic Anhydride: Synthesis and Characterization. J Material Sci Eng. 2016;5:247.
- Heidari A. Manufacturing Process of Solar Cells Using Cadmium Oxide (CdO) and Rhodium (III) Oxide (Rh2O3) Nanoparticles. J Biotechnol Biomater. 2016;6:e125.
- Hinal G and Shabib K. Biological Synthesis of Silver Nanoparticles and Its Antibacterial Activity. J Nanomed Nanotechnol. 2016;7:366.
- Erika M, et al. Synthesis of Iron Nanoparticles using Extracts of Native Fruits of Ecuador, as Capuli (Prunus serotina) and MortiÃƒÂ±o (Vaccinium floribundum). Biol Med (Aligarh). 2016;8:282.
- Khaled EAA, et al. Mesoporous Silica Materials in Drug Delivery System: pH/Glutathione- Responsive Release of Poorly Water-Soluble Pro-drug Quercetin from Two and Three-dimensional Pore-Structure Nanoparticles. J Nanomed Nanotechnol. 2016;7:360.
- Bakare AA, et al. Genotoxicity of Titanium Dioxide Nanoparticles using the Mouse Bone Marrow Micronucleus and Sperm Morphology Assays. J Pollut Eff Cont. 2016;4:156.
- Elayaraja S, et al. Enhancement of Vibriosis Resistance in Litopenaeus vannamei by Supplementation of Biomastered Silver Nanoparticles by Bacillus subtilis. J Nanomed Nanotechnol. 2016;7:352.
- Khaled EAA, et al. pH-controlled Release System for Curcumin based on Functionalized Dendritic Mesoporous Silica Nanoparticles. J Nanomed Nanotechnol. 2016;7:351.
- Pramod K, et al. Synthesis of Dox Drug Conjugation and Citric Acid Stabilized Superparamagnetic Iron-Oxide Nanoparticles for Drug Delivery. Biochem Physiol. 2016;5:194.
- Vinoda BM, et al. Photocatalytic Degradation of Toxic Methyl Red Dye Using Silica Nanoparticles Synthesized from Rice Husk Ash. J Environ Anal Toxicol. 2015;6:336.
- El-Hussein A. Study DNA Damage after Photodynamic Therapy using Silver Nanoparticles with A549 cell line. J Nanomed Nanotechnol. 2016;7:346.
- Mohd Y, et al. Haloperidol Loaded Solid Lipid Nanoparticles for Nose to Brain Delivery: Stability and In vivo Studies. J Nanomed Nanotechnol. 2015;S7:006.
- Hajiyeva FV, et al. Luminescent Properties of Nanocomposites on the Basis of Isotactic Polypropylene and Zirconium Dioxide Nanoparticles. J Nanomed Nanotechnol. 2015;S7:003.
- Shareena DTP, et al. Antibacterial Activity and Cytotoxicity of Gold (I) and (III) Ions and Gold Nanoparticles. Biochem Pharmacol. 2015;4:199.
- Panta PC and Bergmann CP. Raman Spectroscopy of Iron Oxide of Nanoparticles (Fe3O4). J Material Sci Eng. 2015;5:217.
- Valentina I and Eleonora M. Inhaled Micro- or Nanoparticles: Which are the Best for Intramacrophagic Antiinfectious Therapies?. J Infect Dis Diagn. 2016;1:e101.
- Itay L, et al. Tumor Necrosis Factor Related Apoptosis Inducing Ligand-conjugated Near IR Fluorescent Iron Oxide/Human Serum Albumin Core-shell Nanoparticles of Narrow Size Distribution for Cancer Targeting and Therapy. J Nanomed Nanotechnol. 2015;6:333.
- Omolola EF, et al. Metal Oxide Nanoparticles/Multi-walled Carbon Nanotube Nanocomposite Modified Electrode for the Detection of Dopamine: Comparative Electrochemical Study. J Biosens Bioelectron. 2015;6:190.
- Asadi M, et al. Synthesis of Silver Nanoparticles through Chemical Reduction and its Antibacterial Effect. JFDT. 2015.
- López T, et al. Preparation and Characterization of Antiepileptic Drugs Encapsulated in Sol-Gel Titania Nanoparticles as Controlled Release System. Med Chem (Los Angeles). 2015;S2:003.
- Joseph DC and Anil B. Gold Nanoparticles (AuNPs): A New Frontier in Vaccine Delivery. J Nanomedine Biotherapeutic Discov. 2015.
- Krukemeyer MG*, et al. History and Possible Uses of Nanomedicine Based on Nanoparticles and Nanotechnological Progress. J Nanomed Nanotechnol. 2015;6:336.
- Muniz-Miranda M. Application of the SERS Spectroscopy to the Study of Catalytic Reactions by Means of Mono and Bimetallic Nanoparticles. J Anal Bioanal Tech. 2015;6:286.
- Anthony C, et al. Heat Dissipation of Hybrid Iron Oxide-Gold Nanoparticles in an Agar Phantom. J Nanomed Nanotechnol. 2015;6:335.
- Hasan S. A Review on Nanoparticles: Their Synthesis and Types. Research Journal of Recent Sciences. 2015.
- Perrault SD, et al. Mediating tumor targeting efficiency of nanoparticles through design. Nano letters. 2009;9:1909-1915.
- Li JF, et al. Shell-isolated nanoparticle-enhanced Raman spectroscopy. Nature. 2010;464:392-395.
- Zhao W, et al. Paper-based bioassays using gold nanoparticle colorimetric probes. Analytical chemistry. 2008;80:8431-8437.
- Choi HS, et al. Design considerations for tumour-targeted nanoparticles. Nature nanotechnology. 2010;5:42-47.
- Ferrari M. Cancer nanotechnology: opportunities and challenges. Nature Reviews Cancer. 2005;5:161-171.
- Qian X, et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nature biotechnology. 2008;26:83-90.
- Lammers TGGM, et al. Tumour-targeted nanomedicines: principles and practice. British journal of cancer. 2008;99:392-397.
- Bartlett DW, et al. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proceedings of the National Academy of Sciences. 2007;104:15549-15554.
- Ferrari M. Cancer nanotechnology: opportunities and challenges. Nature Reviews Cancer. 2005;5:161-171.
- Tkachenko AG, et al. Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. Journal of the American Chemical Society. 2003;125:4700-4701.
- Winter PM, et al. Molecular imaging of angiogenesis in early-stage atherosclerosis with αvβ3-integrin–targeted nanoparticles. Circulation. 2003;108:2270-2274.
- Medina C, et al. Nanoparticles: pharmacological and toxicological significance. British journal of pharmacology. 2007;150:552-558.
- Murphy CJ, et al. Gold nanoparticles in biology: beyond toxicity to cellular imaging. Accounts of chemical research. 2008;41:1721-1730.
- Hrkach J, et al. Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Science translational medicine. 2012;4:128ra39-128ra39.