Tools For Cancer Therapy Liposomes

Published Date: 02 Nov 2017

[(imp 18) Liposome’s are attractive for drug delivery applications for numerous reasons, including their resemblance to cell membranes in both structure and composition. Additionally, liposomes can be readily formed with nontoxic, non immunogenic, natural and bio-degradable amphiphilic molecules (Haley and Frenkel, 2008; Lasic, 1998.].[(imp 10) Examples of liposome-mediated drug delivery are doxorubicin (Doxil) and daunorubicin (Daunoxome), which are currently being marketed as liposome delivery Systems. Polyethylene glycol (PEG)ylated liposomal doxorubicin (Doxil1, Caelyx1; Alza Pharmaceuticals and San Bruno, CA and USA) has get the most long-lasting circulation, with a terminal half-life about 55 hr in humans [7,9,17].[(umashanker) now a day’s some new class of liposomes is under development i.e Aquasomes, Aquasomes are three-layered structures (i.e., core, coating, and drug) that are self-assembled through non covalent bonds, ionic bonds, and van der Wals forces.14 They consist of a ceramic core whose surface is non covalently modified with carbohydrates to obtain a sugar ball, which is then exposed to adsorption of a therapeutic agent. The core provides structural stability to a largely immutable solid. The surface modification with carbohydrates creates a glassy molecular stabilization film that adsorbs therapeutic proteins with minimal structural denaturation. Thus, these particles provide complete protection of an aqueous nature to the adsorbed drugs against the denaturing effects of external pH and temperature, because there are no swelling and porosity changes with change in pH or temperature.]. Coating of sugar over the ceramic core can be confirmed by using concanavalin A– which is induced aggregation method (determines the amount of sugar coated over core) or by anthrone method (after coating, determines the residual sugar unbound or residual sugar remaining). Furthermore, the adsorption of sugar over the core can also be confirmed by measurement of zeta potential.23-25.

Polymer –oil nanostructured carrier –

(Imp 1) several recently developed drugs encounter delivery issues owing to their high lipophilicity as well as poor aqueous solubility. This study reports the a novel hybrid nanocarrier called as polymer-oil nanostructured carrier (PONC) development, in which highly lipophilic drugs such as all-trans-retinoic acid as well as indomethacin pre-solubilized were dispersed in a polymeric matrix of poly(d,l-lacticco- glycolic acid) (PLGA) in oil phase. Conventional solid lipid nanoparticles tend to slowly release their entrapped drugs for several days to weeks which may be unsuitable for many non-chronic disease conditions (Wong et al., 2007), whereas nanoemulsions made of fine oil droplets may encounter stability issues like Ostwald ripening as well as technical issues such as difficulty to be lyophilized for storage and surface engineered for targeting purposes (Li et al., 2009; Tadros et al., 2004). In novel design of polymer-oil nanostructured carrier (PONC) in a reverse manner, in which liquid oil was dispersed inside a polymeric matrix of poly(d,l-lactic-co-glycolic acid). We have hypothesized that with this PONC design, several advantages could be achieved: (1) the incorporation of oil would enable efficient encapsulation of lipophilic, poorly water-soluble drugs in dissolved state. (2) Meanwhile, the biodegradable, biocompatible PLGA would provide an easily fabricable nanocarrier framework stabilizing the oil/drug components and allowing lyophilization. (3) We learnt from solid lipid nanoparticles that the solid materials tend to pack tightly during particle formation, which drives the loaded drug molecules toward the nanoparticle surface to increase the risk of uncontrolled initial burst releases (Wong et al., 2007). As shown previously, inclusion of oil into solid lipids could introduce room, or "nanostructure", within the particle cores by increasing their amorphosity (Müller et al., 2002; Xue and Wong, 2011a,b). This could promote uniform drug distribution and improve drug release profiles. We expected this same advantage to be equally achievable in PONC. (4) If the drug release kinetics could be modified by the nanostructure of polymeric matrix as predicted, it would open up an opportunity to tailor the drug release kinetics through manipulation of the nanostructure, e.g. by adjusting the polymer grade or polymer-oil ratio.

Inorganic nanocarriers-(imp 16)

Inorganic nanoparticles, in the field of oncology have received increased concentration in the recent past as potential diagnostic as well as therapeutic systems. It has demonstrated successes in tumors especially in imaging and treatment of both in vitro and in vivo with some assure towards clinical trials. Nanoparticles have gained important attention in the recent past because of their unique material along with size-dependent physicochemical properties, which are not possible with traditional lipid or polymer based nanoparticles. Specially, optical, magnetic, and other physical properties, in addition to inertness, stability, and ease of functionalization, make inorganic nanoparticles attractive alternatives to organic nanoparticles for imaging and ablation of malignant tissue.

Magnetic nonoparticles-

Super paramagnetic iron-oxide nanoparticles (SPIONs) possess unique magnetic properties that make them attractive candidates as advanced biomedical materials. They can serve as contrast agents in MRI, as miniaturized heaters capable of killing malignant cells and as colloidal carriers for drug delivery targeted at cancer diagnosis and therapy [143–145]. The super paramagnetic property of iron oxide particles originates from the large magnetic moment they acquire external magnetic field; removing the field eliminates the paramagnetism. The large magnetic moment results in higher signal change or contrast per unit of particles and thus small quantities of SPIO are needed for imaging thereby limiting cellular toxicity. In addition to possessing excellent magnetic properties,

SPIONs are biocompatible and biodegradable and hence have found widespread use in biomedical applications. Upon degradation, the free iron ions released do not appreciably increase the body's native iron pool, get incorporated in hemoglobin in erythrocytes and are thus degraded along normal iron recycling pathways [146]. The most common method of synthesis of SPIONs is by alkaline coprecipitation of Fe(OH)2 and Fe(OH)3 suspensions [147]. Particle size can vary between several nanometers and several hundred Fig. 5. (a) Schematic diagram of paclitaxel (PTX) drug conjugated to PEGylated CNTs. (b) The SWCNT-PTX conjugate decreased the tumor volume to one-third of its original volume containing breast tumors in mice whereas, the unconjugated drug delivery demonstrated lower tumor suppression activity. By permission from the American Association for Cancer Research it is Adapted and reprinted: [132]. Nanometers in diameter [148]. A variety of methods have been employed to functionalize the SPIO particles with a coating of inert polymers including dextran [149], polysaccharides [150], PEG, and polyethylene oxide (PEO) [151] in order to increase their stability, circulation half-life and biocompatibility. A recent development includes the use of thermally cross linked super paramagnetic iron oxide nanoparticles (TCL-SPIONs) for MR imaging and drug delivery. These particles have a layer of PEG on their surface as well as the anti-cancer drug, doxorubicin, incorporated in the polymeric shell of SPIOs [167]. These nanoparticles were efficient in detecting Lewis lung carcinoma and delivering sufficient amount of the drug to tumor tissues with lower toxicity in non-target organs in vivo. The drug released faster under the mildly acidic conditions in the tumor microenvironment than at neutral pH of the vasculature.

Dendrimers (imp 10)

Macromolecular compounds like dendrimers that are comprise a sequence of branches around an inner core and size as well as shape of which can be changed as desired, and therefore, for drug delivery serve as an attractive modality [38–41]. In a recent work by Choi et al. [42], DNA just like polyamidoamine dendrimer clusters have prepared for cancer-cell-specific targeting. They have prepared dendrimer-5FU conjugates by acetylation, which – upon hydrolysis – release free 5FU, thus minimizing the toxicity of 5FU [31,42]. The unique architecture of dendrimers able to for multivalent attachment of imaging probes, and targeting moieties; thus, it can be also used as a highly efficient diagnostic tool for cancer imaging. For computed tomography imaging, Gadolinium-based magnetic resonance imaging dissimilarity agents can operate at a just about 100-fold less concentration as compared to iodine atoms required. Improves the sensitivity of imaging due to targeted to a single site [43,44]. Phase I clinical trials of Starpharma’s dendrimer based microbicide (Viva Gel) are also the first human dendrimer pharmaceutical clinical trials [45].

Conclusion-

The application of nanotechnology in the field of cancer nanotechnology, in the past few years has experienced exponential growth. Nanoparticles provide opportunities for designing as well as tuning properties with other types of therapeutic drugs but that are not possible. They have a brilliant future in new generation of therapeutics cancer. The multidisciplinary field of nanotechnology holds the promise of delivering a technological breakthrough and is moving very fast from concept to reality.