Nano-Sized Drug Delivery
Received: 23-Jul-2013 / Accepted Date: 25-Jul-2013 / Published Date: 01-Aug-2013 DOI: 10.4172/2329-9053.1000e108
Keywords: Drug delivery; Active targeting; Passive targeting; Drug carriers
In the last few decades, pharmacists focused to develop targeted drug delivery systems. The basic aim is to deliver drug molecules directly to the target tissues which Paul Ehrlich in about a century ago mentioned and named it as magic bullets of medicine [1,2]. Generally, pharmaceutical agents tend to distribute equally throughout the body. In addition, to reach the site of action, the drug has to cross vast majority of physiological and biochemical barriers which reduce the bioavailability of drugs. more importantly, After crossing through these barriers drugs should be able to elicit pharmacological action [3,4]. However, Nowadays, rapid advances in molecular biology, chemistry, pharmacy and nanotechnology enable a number of targeted drug delivery systems which can reach the malignant tissues selectively and accurately to the affected sites of the body [2,5].
Targeted drug delivery augments the therapeutic range of drugs in the tissues of interest while reducing the relative concentration of those in the other parts of the body. Targeting of drugs to affected site of the body offers enormous advantages [2,6-8]:
- Provide drug levels within the therapeutic range
- Vastly decrease in toxicity and side effects
- Increase in efficacy of drugs and bioavailability
- Increase drug concentration in the target organ
- Decrease the dosage of drug
There are numerous research and review articles in the literature on targeted drug delivery for cancer, inflammations, HIV in tissues such as brain, prostate, lung, heart, liver, ocular and blood [2,9-13]. Amongst those, cancer has much more attention than other diseases. Different types of drug carriers, varied targeting systems were developed a way to provide effective treatment for this fatal disease .
Types Of Carriers
There are 2 broad drug carriers namely: Particulate drug carriers and macromolecular conjugates. Use of appropriate carriers is one of the most important steps to devise targeting agents . Several carriers such as liposomes, micelles, polymeric nanoparticles, dendrimers, solid lipid nanoparticles, proteins, viruses, Carbon nanotubes, Gold nanoparticles , chitosan nanoparticles metallic nanoparticles are reported for drug targeting [9-17]. A carrier should be biocompatible, biodegradable, hydrophilic and have potential for surface modification. However, the most important aim for this modification is to increase solubility, stability and extended duration of drugs in blood circulation and add a passive or active targeting option to these nanocarriers. Based on physico chemical property of drugs, its target, targeting moiety, better drug loading and release profile are required [15,16,18,19].
Principles of drug targeting
Recognizing the morphological and physiological differences between malignant and normal tissues is essential to achieve effective drug delivery to the tumor tissues. Many different types of nanosystems have been designed and evaluated for drug targeting to tumors. There are 2 main types of targeted therapy drugs which are discussed below [2,20,21].
Passive targeting is to target anatomical and patho-physiological differences of malfunction tissues from normal ones, for example angiogenesis leads to elevated vascular density in tumors, and because of that the gaps between endothelial cells are much larger than endothelial gaps in normal cells. This unique phenomenon called as enhanced permeability and retention (EPR) effect. To take advantage of this effect, nanoparticles must be engineered with ideal size and long circulation [7,14,20,21].
Another types of passive targeting is to track Tumor microenvironment, likewise change in PH, temperature and some enzymes [21,23-25]. The excessive metabolic rates in tumors provide an acidic environment around that the tumor. Shnitzky in 1980 prepared PH-sensitive liposomes . The other approach is temperaturesensitive liposomes. In these kinds of nanoparticles, thermo-sensitive polymer were used which exhibit a lower critical solution temperature (LCST). Surface Modification of liposomes with these polymers give temperature-sensitive functionalities to the liposomes [24,27].
The active targeting involves surface modification of drug carriers by conjugating ligands including proteins, glycolipids, peptides, polysaccharides, glycoproteins, aptamers and monoclonal antibodies which specifically attach to receptors exist at the target site [7,14,20,28].
In summary, as a result of research for the half century on different approaches to develop targeted drug delivery systems and multifunctional nanoparticles, the advantages are clearly demonstrated. However, still there are long way to achieve an ideal targeted drug delivery systems for clinical use [21,30].
- Ehrlich P (1954) The partial function of cells. (Nobel Prize address given on 11 December 1908 at Stockholm). Int Arch Allergy Appl Immunol 5: 67-86.
- Muro S (2012) Challenges in design and characterization of ligand-targeted drug delivery systems. J Control Release 164: 125-137.
- Jaspreet KV, Maram KR, Vinod DL (2005) Nanosystems in Drug Targeting: Opportunities and Challenges. Current Nanoscience 1: 47-64.
- Garnett MC (2001) Targeted drug conjugates: principles and progress. Adv Drug Deliv Rev 53: 171-216.
- Vimukta, Gupta Manish (2011) Targeted drug delivery system: A Review. Research Journal of Chemical Sciences 1.
- Petrak K (2005) Essential properties of drug-targeting delivery systems. Drug Discov Today 10: 1667-1673.
- Jaracz S, Chen J, Kuznetsova LV, Ojima I (2005) Recent advances in tumor-targeting anticancer drug conjugates. Bioorg Med Chem 13: 5043-5054.
- Poelstra K, Prakash J, Beljaars L (2012) Drug targeting to the diseased liver. J Control Release 161: 188-197.
- Beduneau A, Saulnier P, Benoit JP (2007) Active targeting of brain tumors using nanocarriers. Biomaterials 28: 4947-4967.
- Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60: 1615-1626.
- Gupta U, Jain NK (2010) Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting. Adv Drug Deliv Rev 62: 478-490.
- Gunaseelan S, Gunaseelan K, Deshmukh M, Zhang X, Sinko PJ (2010) Surface modifications of nanocarriers for effective intracellular delivery of anti-HIV drugs. Adv Drug Deliv Rev 62: 518-531.
- Marcucci F Lefoulon Fo (2004) Active targeting with particulate drug carriers in tumor therapy: fundamentals and recent progress. Drug Discovery Today 9: 219-228.
- Webster DM, Sundaram P, Byrne ME (2013) Injectable nanomaterials for drug delivery: carriers, targeting moieties, and therapeutics. Eur J Pharm Biopharm 84: 1-20.
- Lehner R, Wang X, Marsch S, Hunziker P (2013) Intelligent nanomaterials for medicine: Carrier platforms and targeting strategies in the context of clinical application. Nanomedicine pii: S1549-9634(13)00033-6.
- Ma Y, Nolte RJM, Cornelissen JJLM (2012) Virus-based nanocarriers for drug delivery. Adv Drug Deliv Rev 64: 811-825.
- Zhang XX, Eden HS, Chen X (2012) Peptides in cancer nanomedicine: Drug carriers, targeting ligands and protease substrates. J Control Release 159: 2-13.
- Phillips MA, Gran ML, Peppas NA (2010) Targeted nanodelivery of drugs and diagnostics. Nano Today 5: 143-159
- Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release 161: 175-187.
- Danhier F, Feron O, Preat V (2010) To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148: 135-146.
- Maruyama K (2011) Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev 63: 161-169.
- Cajot S, Van Butsele K, Paillard A, Passirani C, Garcion E (2012) Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs. Acta Biomater 8: 4215-4223.
- Chilkoti A, Dreher MR, Meyer DE, Raucher D (2002) Targeted drug delivery by thermally responsive polymers. Adv Drug Deliv Rev. 54: 613-630.
- Torchilin VP (2006) Multifunctional nanocarriers. Adv Drug Deliv Rev 58: 1532-1555.
- Yatvin MB, Kreutz W, Horwitz BA, Shinitzky M (1980) pH-sensitive liposomes: possible clinical implications. Science 210: 1253-1255.
- Cho K, Wang Xu, Shuming Nie, Zhuo Chen, Shin DM (2008) Therapeutic Nanoparticles for Drug Delivery in Cancer. Clinical Cancer Research 14: 1310
- Lee JH (2010) Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates. Adv Drug Deliv Rev 62: 592-605.
- Nielsen UB, Marks JD (2000) Internalizing antibodies and targeted cancer therapy: direct selection from phage display libraries. Pharmaceutical Science and Technology Today 3: 282-291.
- Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M (2011) Multi-stage delivery nano-particle systems for therapeutic applications. Biochim Biophys Acta. 1810: 317-329.
Citation: Mostafavi SH, Jayachandra Babu R (2013) Nano-Sized Drug Delivery. J Mol Pharm Org Process Res 1: e108 Doi: 10.4172/2329-9053.1000e108
Copyright: ©2013 Mostafavi SH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited