Nanoparticles

Definition:

Nanoparticles are the colloidal particulate systems with size ranging between 1-1000 nm [1].

Classification:

Based on the arrangement of drug and polymer matrix, nanoparticles can be classified into two types: nanospheres and nanocapsules (Fig. 1). In nanospheres, drugs are either adsorbed or entrapped inside the polymeric matrix. In nanocapsules, drugs are confined to the inner liquid core while the external surface of nanoparticles is covered by the polymeric membrane [2].

Schematic representation of nanosphere

Summary:

In the recent years, polymeric nanoparticles have gained considerable attention as potential drug delivery systems due to its targetability to particular organ/tissue and ability to deliver protein and peptide via oral route. Nanoparticles for drug delivery are generally made up of biocompatible and biodegradable polymers obtained from either natural or synthetic source [3]. Natural polymers include chitosan, albumin, rosin, sodium alginate and gelatin while, synthetic polymers include poly (lactic acid) PLA, poly (D,L-glycolide), poly (lactide-co-glycolide), poly (caprolactones) (PCL) and poly (cyanoacrylates) [5]. The kinetics of drug release from nanoparticles depends on the strength of hydrophobic interactions between the polymer and drug and polymer degradation rate. The uptake and distribution of nanoparticles depend on its size. Nanoparticles of size ~10 nm are utilized for extended circulation, while ~100 and ~200 nm particles are utilized for passive targeting and intracellular drug delivery respectively [6]. Though nanoparticles have many advantages over other conventional drug delivery systems certain properties like surface hydrophobicity and surface charge needs to be altered so as to increase the uptake of nanoparticles into cells. This can be done by judiciously manipulating the use of polymers. Coating the nanoparticles with chitosan which is positively charged significantly enhances the uptake and modulates the drug efflux of anticancer agents [7]. Moreover, attachment of poly(ethylene glycol) moieties to the surface of nanoparticles increases the hydrophilicity and hence decreases the uptake by macrophages. Recent studies by Yoncheva et al. concluded that amino-pegylated poly(methyl vinyl ether-co-maleic anhydride) nanoparticles were able to cross the cell membrane of the absorptive enterocytes in a better way. Nanoparticles are characterized by a variety of techniques such as dynamic light scattering (DLS), electron microscopy (TEM or SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), x-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), and magnetic resonance (NMR).

Advantages of nanoparticles [1,9, 10, 11]

a) Longer shelf-stability

b) High carrier capacity

c) Ability to incorporate hydrophilic and hydrophobic drug molecules

d) Can be administered via different routes

e) Longer clearance time

f) Ability to sustain the release of drug

g) Can be utilized for imaging studies

h) Increase the bioavailability of drugs

i) Targeted delivery of drugs at cellular and nuclear level

j) Development of new medicines which are more safe

k) Prevent the multi-drug resistance mediated efflux of chemotherapeutic agents

l) Product life extension

Disadvantages of nanoparticles [12,13, 14]

a) Involves higher manufacturing costs which may in turn lead to increase in the cost of formulation

b) Involves use of harsh toxic solvents in the preparation process

c) May trigger immune response and allergic reactions

d) Extensive use of poly(vinyl alcohol) as stabilizer may have toxicity issues

Books on nanoparticles

1. M.S. Cartiera, "An analysis of the interaction and intracellular fate of nanoparticles in epithelial cells : Application in oral delivery of plga nanoparticles encapsulating curcumin for treatment of cystic fibrosis," Yale University, 2007., 2007, pp. xiv, 121 leaves.

2.W. Machtle, L. Borger and SpringerLink (Online service), "Analytical ultracentrifugation of polymers and nanoparticles," Springer laboratory, Springer-Verlag Berlin Heidelberg, Berlin, Heidelberg, 2006.

3.W. C. W. Chan, Bio-applications of nanoparticles, Springer Science + Business Media ; Landes Bioscience, [New York] Austin, Tex., 2007.

4. A. Elaissari, Colloidal nanoparticles in biotechnology, Wiley-Interscience, Hoboken, N.J., 2008.

Articles on nanoparticles

1.E. Grill, N. W. Johnston, T. Sadhukha and J. Panyam, A review of select recent patents on novel nanocarriers, Recent Pat Drug Deliv Formul 3(2009), no. 2, 137-142.

2.R. Singh and J. W. Lillard, Jr., Nanoparticle-based targeted drug delivery, Exp Mol Pathol 86 (2009), no. 3, 215-223.

3.Vauthier and K.Bouchemal, Methods for the preparation and manufacture of polymeric nanoparticles, Pharm Res 26 (2009), no. 5, 1025-1058.

4.Bonnemain, [nanoparticles: The industrial viewpoint. Applications in diagnostic imaging], Ann Pharm Fr 66 (2008), no. 5-6, 263-267.

5.M. M. Bailey and C. J. Berkland, Nanoparticle formulations in pulmonary drug delivery, Med Res Rev 29 (2009), no. 1, 196-212.

6.W. H. De Jong and P. J. Borm, Drug delivery and nanoparticles:Applications and hazards, Int J Nanomedicine 3 (2008), no. 2, 133-149.

7.Y. Liu, H. Miyoshi and M. Nakamura, Nanomedicine for drug delivery and imaging: A promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles, Int J Cancer 120 (2007), no. 12, 2527-2537.

8. D. B. Buxton, S. C. Lee, S. A. Wickline and M. Ferrari, Recommendations of the national heart, lung, and blood institute nanotechnology working group, Circulation 108 (2003), no. 22, 2737-2742.

9. M. Nahar, T. Dutta, S. Murugesan, A. Asthana, D. Mishra, V. Rajkumar, M. Tare, S. Saraf and N. K. Jain, Functional polymeric nanoparticles: An efficient and promising tool for active delivery of bioactives, Crit Rev Ther Drug Carrier Syst 23 (2006), no. 4, 259-318.

10. K. S. Soppimath, T. M. Aminabhavi, A. R. Kulkarni and W. E. Rudzinski, Biodegradable polymeric nanoparticles as drug delivery devices, J Control Release 70 (2001), no. 1-2, 1-20

References:

1.I.Bala, S. Hariharan and M. N. Kumar, Plga nanoparticles in drug delivery: The state of the art, Crit Rev Ther Drug Carrier Syst 21 (2004), no. 5, 387-422.

2.J. Kreuter, " Nanoparticles as drug delivery system," Encyclopedia of nanoscience and nanotechnology, H. S. Nalwa (Editor), American Scientific Publishers, Stevenson Ranch, Calif., 2004, pp. 161-180.

3.R. Langer, Biomaterials in drug delivery and tissue engineering: One laboratory's experience, Acc Chem Res 33 (2000), no. 2, 94-101.

4.M. Nahar, T. Dutta, S. Murugesan, A. Asthana, D. Mishra, V. Rajkumar, M. Tare, S. Saraf and N. K. Jain, Functional polymeric nanoparticles: An efficient and promising tool for active delivery of bioactives, Crit Rev Ther Drug Carrier Syst 23 (2006), no. 4, 259-318.

5.B. Malaekeh-Nikouei, S. A. Sajadi Tabassi and M.R. Jaafari, The effect of different grades of plga on characteristics of microspheres encapsulated with cyclosporine a, Curr Drug Deliv 3 (2006), no. 4, 343-349.

6.C. Fang, B. Shi, Y. Y. Pei, M. H. Hong, J. Wu and H. Z. Chen, In vivo tumor targeting of tumor necrosis factor-alpha-loaded stealth nanoparticles: Effect of mepeg molecular weight and particle size, Eur J Pharm Sci 27 (2006), no. 1, 27-36.

7.K. Dharmala, J. W. Yoo and C. H. Lee, Development of chitosan-sln microparticles for chemotherapy: In vitro approach through efflux-transporter modulation, J Control Release 131 (2008), no. 3, 190-197.

8.K. Yoncheva, M. N. Centelles and J. M. Irache, Development of bioadhesive amino-pegylated poly(anhydride) nanoparticles designed for oral DNA delivery, J Microencapsul 25 (2008), no. 2, 82-89.

9.S. Gelperina, K. Kisich, M. D. Iseman and L. Heifets, The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis, Am J Respir Crit Care Med 172(2005), no. 12, 1487-1490.

10.M. Susa, A. K. Iyer, K. Ryu, F. J. Hornicek, H. Mankin, M. M. Amiji and Z. Duan, Doxorubicin loaded polymeric nanoparticulate delivery system to overcome drug resistance in osteosarcoma, BMC Cancer 9 (2009), 399.

11.H. K. Sajja, M. P. East, H. Mao, Y. A. Wang, S. Nie and L. Yang, Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect, Curr Drug Discov Technol 6 (2009), no. 1, 43-51.

12.R. M. Mainardes, M. C. Urban, P. O. Cinto, N. M. Khalil, M. V. Chaud, R. C. Evangelista and M. P. Gremiao, Colloidal carriers for ophthalmic drug delivery, Curr Drug Targets 6 (2005), no. 3, 363-371.

13.W. H. De Jong and P. J. Borm, Drug delivery and nanoparticles:Applications and hazards, Int J Nanomedicine 3 (2008), no. 2, 133-149.

14.N. K. Varde and D. W. Pack, Microspheres for controlled release drug delivery, Expert Opin Biol Ther 4 (2004), no. 1, 35-51.