Biocompatibility cytotoxicity

Keywords Gene therapy, natural polymers, nonviral vectors, biocompatibility, cytotoxicity... 

The versatile properties and manufacturability of polymers has evoked immense interest in developing a class of biomaterials with the potential to interface with biological systems [1]. However, polymers are prone to pathogenic attack resulting in deterioration of properties, malfunction and so on. Various methods such as the ionic binding technique, incorporation of metal particles/metal oxides/nanoparticles (NP) and physico-chemical modification via, e.g., the addition of quaternary ammonium salts and blending with antimicrobial polymers, have been explored for the fabrication of bactericidal materials [2], However, these methods can result in reduced biocompatibility, cytotoxicity and eco-toxicity. 

An adequate treatment of the subject should involve a discussion of production materials. Thus we have referred to a large variety of materials (i.e., natural and synthetic polymers) for nanofibre fabrication, including the choice and use of them, and a description of how their properties influence processing parameters and properties (biocompatibility, cytotoxicity, etc.) of the product. 

Although the initially reported tissue compatibility tests for subcutaneous implants of poly(BPA-iminocarbonate) were encouraging (41,42), it is doubtful whether this polymer will pass more stringent biocompatibility tests. In correspondence with the properties of most synthetic phenols, BPA is a known irritant and most recent results indicate that BPA is cytotoxic toward chick embryo fibroblasts in vitro (43). Thus, initial results indicate that poly(BPA-iminocarbonate) is a polymer with highly promising material properties, whose ultimate applicability as a biomaterial is questionable due to the possible toxicity of its monomeric building blocks. 

As mentioned previously (and discussed in detail in Sec. IX), contact lens products have specific guidelines that focus on compatibility with the contact lens and biocompatibility with the cornea and conjunctiva [75], These solutions are viewed as new medical devices and require testing with the contact lenses with which they are to be used. Tests include a 21-day ocular study in rabbits and employ the appropriate types of contact lenses with which they are to be used and may include the other solutions that might be used with the lens. Additional tests to evaluate cytotoxicity potential, acute toxicity, sensitization potential (allergenicity), and risks specific to the preparation are also required [75-77], These tests are sufficient to meet requirements in the majority of countries, though testing requirements for Japan are currently much more extensive. 

Despite the evidence for the cytotoxicity of CNTs, there are an increasing number of published studies that support the potential development of CNT-based biomaterials for tissue regeneration (e.g., neuronal substrates [143] and orthopedic materials [154—156]), cancer treatment [157], and drug/vaccine delivery systems [158, 159]. Most of these applications will involve the implantation and/or administration of such materials into patients as for any therapeutic or diagnostic agent used, the toxic potential of the CNTs must be evaluated in relation to their potential benefits [160]. For this reason, detailed investigations of the interactions between CNTs/CNT-based implants and various cell types have been carried out [154, 155, 161]. A comprehensive description of such results, however, is beyond the scope of this chapter. Extensive reviews on the biocompatibility of implantable CNT composite materials [21, 143, 162] and of CNT drug-delivery systems [162] are available. 

Olbrich, C. and Muller, R.H., Tabatt, K., Kaiser, O., Schulze, C., and Schade, R., Stable biocompatible adjuvants — a new type of adjuvant based on solid lipid nanoparticles a study on cytotoxicity, compatibility and efficacy in chicken, Alternatives to Laboratory Animals, 2002, 30, 443 158. 

Biocompatibility is an essential property of new biomaterials for drug delivery. Biocompatibility is always assessed with respect to specific applications and may be assessed with respect to cytotoxicity, allergic responses, irritation, inflammation, mutagenicity, teratogenicity, and carcinogenicity (Katti el al., 2002). The reviews by Katti et al. (2002) and Domb et al. (1997) provide good discussions on the biocompatibility studies that have been conducted with polyanhydrides over the past two decades. 

See also Luminescent dendrimers antibacterial, 26 799 biocompatibility studies of, 26 800-801 in catalysis, 26 805-806 in cell targeting, 26 797-798 as chelators, 26 806-807 core and interior shells of, 26 789 cytotoxicity of, 26 800-801 in drug delivery, 26 792-795 in gene transfection, 26 791-792 as imaging agents, 26 795-797 luminescent, 26 801-804 medical applications of, 26 791-801 micelle-mimetic behavior of, 26 789 multiphoton applications of, 26 803-804... 

As was demonstrated, a variety of polymeric materials are used for preparation of dye-doped beads. Dye-doped silica beads are also extremely popular due to their chemical robustness, biocompatibility and simplicity in preparation and further functionalization of the surface [55]. Thus, polymeric, silica and Ormosil beads (which occupy intermediate position) are widely used as nanosensors and labels. On the other hand, quantum dots possess much higher cytotoxicity which often limits their application in biological systems. 

The tests for in vitro biocompatibility were performed on normal cells (Vero) and tumor cells (glioblastoma). No cytotoxicity was detected in cells (normal or tumor) cultured with red and white onion extracts at low concentrations (between 0% and 1%), the cell viability being aronnd 90%. At higher concentration, the viability decrease slowly at 80% (Fig. 41.4a). On the other hand, garlic extracts indnce toxicity both on normal and tnmor cells at very low concentrations (Fig. 41.4b). 

Be biocompatible (biomaterial) with the underlying epithelia by means of complete absence of cytotoxicity, ciliotoxicity, or other type of irreversible alterations of the cell membrane components ... 

Artificial materials designed for the biomedical use should be biocompatible, i.e. free of adverse effects on cells and tissues, such as cytotoxicity, immimogenicity, mutagenicity and carcinogenicity. Biocompatible materials can be constructed as bioinert, i.e. not allowing adsorption of proteins and adhesion of... 

ISO 10993 standards for evaluating biocompatibility, ISO 10993-5, Biological evaluation of medical devices—Part 5 Tests for cytotoxicity in vitro methods. 

The scientific community was attracted to the study of liposomes due to the relatively simple procedure of their preparation. Moreover, if prepared from natural phospholipids, they are biocompatible, and possess low cytotoxicity, low immunogenicity, and biodegradability [304], Liposomes, however, have two main disadvantages the structural instability both in vitro and in vivo, and low cell specificity [304], To increase the stability, the structure of the phospholipid layer has been modified to include artificial lipids and/or cholesterol. Polymerizable vesicles have also been prepared [305]. It is obvious that the biocompatibility of these modified systems has to be addressed. 

Poly-(3-hydroxybutanoic acid) (PHB), belongs to the large family of poly-(hydroxyalkanoates) (PHAs), high molecular weight natural polymers produced by various microorganisms and stored in cell cytoplasm (200). Low molecular weight PHB, also present in bacteria and are primarily involved in transport of ions and DNA across inner bacterial membrane (201). PHB could be developed as a valuable biocompatible material with possible applications in gene delivery after cytotoxic, safety, and efficacy evaluations. 

---