Ceramic nanoparticles: Recompense, cellular uptake and toxicity concerns

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Table I. Classification of nanoparticles with specific characteristics.

S. No.	Types of nanoparticles	Characteristics	Materials	Advantages	Disadvantages	Applications	References
1.	Ceramic nanoparticles	Ceramic nanoparticles mostly consist of oxides, nitrides or carbides and are mainly used for coatings, because of their heat resistance and chemical inertness	Calcium phosphates, silica, alumina, zirconium and titanium dioxide	High mechanical strength, good body response, pH and temperature resistant, high stability, high load capacity, ease of incorporation into hydrophobic and hydrophilic systems, and different routes of administration (oral, inhalation, etc.)	High density, low biodegradability, highly toxic	Drug delivery, tissue engineering (ceramic nanoscaffolds), diagnostics and biosensors, drug carrier for photodynamic therapy	Singh et al. (2013)
2.	Polymeric nanoparticles	Polymeric nanoparticles are macromolecules composed of a large number of repeating units organized inchain-like molecular architecture exhibiting a multiplicity of compositions, structures, and properties	Gelatins, chitosan, PLA, PLGA, PCL, PGA	Biodegradable, biocompatible, higher bioavailability, ease of functionalization	Cytotoxicity, lack of suitable large-scale production method	Drug delivery, gene therapy to breast cancer, in multiple sclerosis	Alyautdin et al. (2001)
3.	Solid lipid nanoparticles (SLN)	An SLN (average diameter between 10 to 1000 nm) is generally spherical in shape andconsists of a solid lipid core stabilized by a surfactant	Fatty acids, acylglycerols, waxes, surfactant, phospholipid, sphingomyelins, bile salts(sodium taurocholate), and sterols (cholesterol)	Much stable, greater ease of biodegradation, do not show biotoxicity, applicable to deliver drugs orally, topically, or via inhalation	Cannot be used for the shear sensitive substances like DNA, albumin and erythropoietin because the extent of shear produced in the high Pressure homogenization technique can degrade them	Oral and parenteral drug delivery, controlled and site specific drug delivery,clinical medicine and research	Muller et al (2000)
4.	Liposomes	These are concentric bilayered vesicles generally composed of a monolayer of lipids surrounded by a phospholipid membrane	Lecithins (SLP-WHITE, SLP-PC70 and PL30S)	Long residency time, good biocompatibility profile, better control of therapeutic drug delivery	Limited biological stability, restricted to cosmetic uses only and not widely used therapeutically	Fungal and protozoal infections, metastatic breast cancer, malignant lymphomatous meningitis	Muller et al (2002)
5.	Nanocrystals	Nanocrystals are aggregates of molecules with at least one dimension ≤ 100nm that can be combined into a crystalline form of the drug surrounded bya thin coating of surfactant	Dispersion media for the drug nanocrystals -aqueous media (water-ethanol mixtures, isotonic water-glycerol mixtures) or non-aqueous dispersion (PEG or oils)	Formulation of poorly soluble drugs with increased bioavailability, applicable for both oral and parenteral deliveries	Potential contamination of the product by erosion of the milling material, relatively long milling times for hard crystalline drugs, and limited scaling up due to the weight of large scale pearl mills	Extensive use in material research, chemical engineering, and as quantum dots for biological imaging, immunosuppressant, antihyperlipidemic	Dubertret et al (2002), Shibahara et al (2004)
6.	Nanotubes (buckytubes)	Nanotubes are of organic/inorganic in composition, possesself-assembling sheets of atoms mostly carbon arranged in tubes	These are soluble fullerene derivatives, such as C60	Nanotubes have large internal volumes and posess external surface which can be easily functionalized	Toxic in nature and may cause cell death via an oxidative stress pathway	Used asbiopersistent fibers	Porter et al. (2007)
7.	Dendrimers	Dendrimers are a family of nanosized, 3D polymeric structure, unique tree-like branching and compact spherical geometry in solution	Branched polymerssuch as Polyamidoamine (PAMAM), poly(L-glutamic acid), polyethyleneimine, polypropylene mine, and polyethylene glycol	Higher degree of size control and extent of branching, ease of modification and preparation, high aqueous solubility, large number of chemically versatile surface groups	Premature drug release into the systemic circulation causing nonspecific toxicity, release kinetics of the encapsulated drug remains a challenging task	Drug delivery of genetic transfection agent and chemotherapeutic drugs, photodynamicswater soluble dendrimer based contrast agents for computed tomography	Medina and El-Sayed Mohd (2009)

Table II. Methodology for nanoceramic preparation.

S.No.	Methods for synthesis	Starting materials	Principle	Advantages	References
1.	Microemulsion precipitation	Metal salts, surfactant (and co-surfactant), organic solvent	This method involves addition of appropriate amounts of surfactants to a water oil system (w/o) for the preparation of thermally stable emulsion systems	Prevents agglomeration of the particles formed in the individual bubbles	Lade et al. (2000)
2.	Hydrothermal synthesis	Metal salts, alkoxides, hydroxides, organic solvent	This method is based on the principle of liquid nucleation model including theories of chemical equilibrium, chemical kinetics and thermodynamic properties of aqueous systems under hydrothermal conditions	Offers direct oxidation of powders, having narrow size distribution thus avoid calcination step	Riman et al. (2002)
3.	Sol-to-gel process	Metal alkoxides, organic solvent	Solution of appropriate precursors such as metals/metal organic compounds is converted into homogeneous oxide networks i.e gel form by hydrolysis and condensation	Gives high degree of homogeneity, less requirement of atomic diffusion during the solid-state calcinations	Zhang (2004)
4.	Aerogel method	Metal salts, organic solvent	The ultrafine particles are prepared by solid-to- particle conversion and liquid-to-particle conversion	It is a convenient and cost effective method for large scale industrial production of multifacet materials	Gash et al. (2001)
5.	Pechini -Citrate gel method	Metal nitrates, citrate acid, ethylene glycol	This involves polyesterificationof chelates between carbonyl ligands of citric acid and metal ions while heating with polyalcohols	Gives good homogeneity and control of stoichiometry for preparation of multi-component compositions with lowered minimal decomposition temperatures	Zhang (2004)
6.	Low temperature combustion (LCS) method	Metal nitrates, citrate acid, sucrose(in sucrose method)	This is based on gelling and subsequent combustion of an aqueous solution containing desired metallic salts and some organic fuel	A novel, extremely facile, time saving and energy-efficient method for synthesis of ultra fine powders	Zhang (2004)

Figure 1. Classification of ceramic nanoparticulate systems on the basis of their composition and construct.

Figure 2. Cytosolic delivery of therapeutic agents through nanoparticle carriers: The uptake of nanoparticles is mediated by clathrin endocytosis, by the formation of endosomes. In the presence of organelle lysosomes, endosomes get degraded and nanoparticles freely release the drug into cytoplasm at the targeted site.

Figure 3. Toxicity of nanoparticles to specific organs: The nature of central elements such as cadmium and selenium, together with surface modifications, could cause collateral damage of various organs and alter the plasma membrane of the cell.

Singh D, Dubey P, Pradhan M, Rawat M. 2013. Ceramic nanocarriers: versatile nanosystem for protein and peptide delivery. Expert Opin Drug Deliv. 10:241–259.

 PubMed Web of Science ®Google Scholar

Alyautdin RN, Reichel A, Lobenberg R, Ramge P, Kreuter J, Begley DJ. 2001. Interaction of poly(butylcyanoacrylate) nanoparticles with the blood-brain barrier in vivo and in vitro. J Drug Target. 9: 209–221.

 PubMed Web of Science ®Google Scholar

Muller RH, Mader K, Gohla S. 2000. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm. 50:161–177.

 PubMed Web of Science ®Google Scholar

Muller RH, Radtke M, Wissing SA. 2002. Solid lipid nanoparticles (SLN) and Nanostructured lipid carriers (NLC) in cosmetic and dermatological preparation. Adv Drug Deliv Rev. 54:5131–5155.

 Google Scholar

Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A. 2002. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science. 298:1759–1762.

 PubMed Web of Science ®Google Scholar

Shibahara A, Hoshino A, Hanaki K, Suzuki K, Yamamoto K. 2004. On the cyto-toxicity caused by quantum dots. Microbiol Immunol. 48:669–675.

 PubMed Web of Science ®Google Scholar

Porter AE, Gass M, Muller K, Skepper JN, Midgley PA, Welland M. 2007. Direct imaging of single-walled carbon nanotubes in cells. Nat. Nanotechnol. 2:713–717.

 PubMed Web of Science ®Google Scholar

Medina SH, El-Sayed Mohd EH. 2009. Dendrimers as carriers for delivery agents. Chem Rev. 109:3141–3157.

 PubMed Web of Science ®Google Scholar

Lade M, Mays H, Schmidt J, Willumeit R, Schomacker R. 2000. On the nanoparticle synthesis in microemulsions: detailed characterization of an applied reaction mixture. Colloids Surf A Phys Chem. 163:3–15.

 Web of Science ®Google Scholar

Riman RE, Suchanek WL, Lencka MM. 2002. Hydrothermal crystallization of ceramics. Ann Chim Sci Mat. 27:15–36.

 Web of Science ®Google Scholar

Zhang L. 2004. Preparation of multi-component ceramic nanoparticles. CISM. 8–21.

 Google Scholar

Gash AE, Tilltson TM, Satcher JH, Hrubesh LW, Simpson RL. 2001. New sol-gel synthetic route to transition and main group metal oxide aerogels using inorganic salt precursors. J Non-cryst Solids. 285:22–28.

 Web of Science ®Google Scholar