The Tools For Cancer Therapy Liposomes Biology Essay

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Liposomes 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, nonimmunogenic, 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, San Bruno, CA, USA) has achieved the most prolonged circulation to date, with a terminal half-life of 55 hours 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 noncovalent bonds, ionic bonds, and van der Wals forces.14 They consist of a ceramic core whose surface is noncovalently 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 concanavalin A-induced aggregation method (determines the amount of sugar coated over core) or by anthrone method (determines the residual sugar unbound or

residual sugar remaining after coating). 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)Many recently developed drugs encounter delivery issues due to their high lipophilicity and poor aqueous solubility. This study reports the development of a novel hybrid nanocarrier known as polymer-oil nanostructured carrier (PONC), in which highly lipophilic drugs such as all-trans-retinoic acid (ATRA) and indomethacin pre-solubilized in oil phase were dispersed in a polymeric matrix of poly(d,l-lacticco- glycolic acid) (PLGA). 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 surfaceengineered 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 within a polymeric matrix of poly(d,l-lactic-co-glycolic acid) (PLGA). We 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 have received increased attention in the recent past as potential diagnostic and therapeutic systems in the field of oncology. Inorganic nanoparticles have demonstrated successes in imaging and treatment of tumors both ex vivo and in vivo, with some promise towards clinical trials. nanoparticles have gained significant attention in the recent past due to their unique material- and size-dependent physicochemical properties, which are not possible with traditional lipid or polymerbased nanoparticles. In particular, 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 superparamagnetic property of iron oxide particles originates from the large magnetic moment they acquire in the presence of an 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, thefree 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 illustration of paclitaxel (PTX) drug conjugated to PEGylated CNTs.

(b) The SWCNT-PTX conjugate reduced the tumor volume to one-third of its original

volume in mice containing breast tumors, while the delivery of the unconjugated drug

demonstrated lower tumor suppression activity. Adapted and reprinted by permission from the American Association for Cancer Research: [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)

Dendrimers are macromolecular compounds that comprise a series of branches around an inner core, the size and shape of which can be altered as desired, and hence serve as an attractive modality for drug delivery [38-41]. In a recent work by Choi et al. [42], DNA assembled polyamidoamine dendrimer clusters were 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 enables for multivalent attachment of imaging probes, as well as targeting moieties; thus, it can be also used as a highly efficient diagnostic tool for cancer imaging. Gadolinium-based magnetic resonance imaging contrast agents can operate at an approximately 100-fold less concentration than iodine atoms required for computed tomography imaging. They can be targeted to a single site, which improves the sensitivity of

imaging [43,44]. Phase I clinical trials of Starpharma's dendrimerbased microbicide (VivaGel) are also the first human dendrimer pharmaceutical clinical trials [45].

Conclusion-

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

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