Nanotechnology in Medicine. Группа авторов

producersChemical structureApplicationsReferencesXanthan gumBacteria from Xanthomonas genus.Backbone of repeating sub‐units, branched or not, consisting of 3–8 monosaccharides, such as D‐glucose, D‐mannose and D‐glucuronic acid. Molecular weight: up to 2000 kDa.Food Cosmetics PharmaceuticsJansson et al. (1975), Laws et al. (2001), Borges and Vendruscolo (2008), and Lopes et al. (2015)CurdlanBacteria from Agrobacterium (previously taxonomically classified as Alcaligenes), Rhizobium, Bacillus, and Cellulomonas genus.D‐glucose units linked by β‐(1➔3) glycosidic bounds. Molecular weight: up to 2000 kDa.Food Cosmetics PharmaceuticsTabernero et al. (2019)PullulanYeasts of Aureobasidium genus.Maltotriose trimer made up of α‐(1 → 6)‐linked (1 → 4)‐α‐D‐triglucosides. Molecular weight: up to 1000 kDa.Foods Cosmetics PharmaceuticsSingh et al. (2008)Gellan gumBacteria from Sphingomonas (formerly known as Pseudomonas elodea).Linear tetrasaccharide repeat unit consisting of (1➔4)‐L‐rhamnose‐(α‐1➔3)‐D‐glucose‐(β‐1➔4)‐D‐glucose‐(β‐1➔4)‐D‐glucose‐(β‐1➔). Molecular weight: ≈500 kDa.Food CosmeticsMorris et al. (2012)EmulsanAcinetobacter calcoaceticus and Acinetobacter venetianus.Polysaccharide backbone (three amino sugars in the ratio 1 : 1 : 1) with O‐acyl and N‐acyl fatty acid side chains (10–20 carbons representing 5–23% [w/w] of the polymer). The amino groups are either acetylated or covalently linked by an amide bond to 3‐hydroxybutyric acid. Molecular weight: ≈1000 kDa.Petrochemistry CosmeticsBelsky et al. (1979), Gorkovenko et al. (1997), and Panilaitis et al. (2007)AlginateAlgae (Laminaria and Ascophyllum) genus.α‐L‐guluronic and β‐D‐mannuronic acid residues linked by β‐(1–4) glycosidic bound. Molecular weight: 10–600 kDa.Food Pharmaceutics CosmeticsFAO (n.d.) http://www.fao.org/3/y4765e/y4765e07.htm and Liang et al. (2015)BotriospheranFilamentous fungus of Botryosphaeria rhodina species and some bacterial isolates.D‐glucose residues bonded by a β‐(1 → 3;1 → 6). Molecular weight: ≈4875 kDa.CosmeticsSelbmann et al. (2003) and Silva et al. (2008)Bacterial celluloseSpecies of nonpathogenic aerobic bacteria, mainly belonging to the genera Gluconacetobacter, Alcaligenes, Rhizobium, Agrobacterium, and Sarcina.β‐D‐glucopyranose units linked to each other by β‐(1➔4) glycosidic bonds.Food Pharmaceutics Cosmetics PaperIguchi et al. (2000), Belgacem and Gandini (2008), and Klemm et al. (2005)ChitosanFilamentous fungi from Mucorales genera and some bacteria.Molecular weight: 100–300 kDa.Food Pharmaceutics CosmeticsKaur et al. (2012), Campos‐Takaki et al. (2014), and Lecointe et al. (2019)Figure 2.2 Biopolymers and building blocks obtained by fermentation.Figure 2.3 Chemical structure of (a) poly(ε‐caprolactone) (PCL), (b) poly(lactic acid) (PLA), (c) poly(glycolic acid) (PGA), and (d) poly(glycolic–lactic acid) (PGLA).Source: Franchetti and Marconato (2006).

       Methyl methacrylate (MMA), a polymer often prepared using benzoyl peroxide as an initiator, is commonly used in the production of dental prostheses, and its toxicity cannot be neglected. When the polymerization reaction is incomplete, monomer residues in the dental prosthesis dissolve in the oral cavity and, according to reports, may cause irritations, allergies, and inflammatory and infectious processes such as stomatitis and cheilitis (Kanzaki et al. 1989; Helton and Storrs 1994; Gebhardt and Geier 1996);

       In an analysis of the acute toxicity of polypropylene, polyethylene, and polyvinyl chloride (PVC), or those composed of hazardous monomers (e.g. acrylonitrile‐butadiene‐styrene [ABS], and epoxides) which are extensively used, it was observed that after leaching processes there is the release of hydrophobic compounds that are toxic to the environment and living organisms (Lithner et al. 2012).

2.3 Applications of Biopolymers in Nanoparticles, Nanofibers, and Drug Delivery Systems of Therapeutic Importance

      Due to the toxicity of synthetic polymers derived from petroleum and the problems they can cause to the environment and the health of organisms, biopolymers have been widely used in the development of therapeutic nanotechnological tools. In addition, some biopolymers, such as chitin and its derivatives, also exhibit biological properties, such as antitumor and antimicrobial activities, which can be enhanced through nanotechnological strategies (Adhikari and Yadav 2018).

Table 2.2 presents recently reported nanotechnological devices (nanoparticles [NPs], nanofilms, nanofibers) based on biopolymers with antitumor and antimicrobial effects that have been developed for the design of tissue prostheses and in tests for the detection of various diseases.

      As indicated in Table 2.2, the biopolymers in the nanocarrier systems contain hydroxyl, carboxyl, and amine groups that have good intermolecular interaction with biological surfaces and biological fluid molecules. In addition, some low‐molecular weight biopolymers are necessary for the stabilization in nanosystems and even interaction with blood serum proteins which easily adhere on positively charged surfaces and cause aggregation and opsonization. These convenient physicochemical and biological characteristics are the reason why biopolymers of microbial origin are considered great alternatives for the pharmaceutical industry, mainly to the design of new drug delivery systems (Jacob et al. 2018). Some antitumor drugs have limited solubility in aqueous media, which compromises their distribution in the body and sometimes their antitumor activity. As noted in Table 2.2, the use of nanocarrier systems based on biopolymers improves absorption and distribution as well as enhances the activity of antitumor agents in the body (Eroglu et al. 2017). In the case of antibiotics, the use of nanocarrier systems improves pharmacokinetics and biodistribution aspects, decreases toxicity, enhances the antibacterial activity, and improves target selectivity (Drulis‐Kawa and Dorotkiewicz‐Jach 2010; Alhariri et al. 2013). The use of modified biopolymers is also very important for the development of drug delivery systems for antitumor and antimicrobial applications. Modifications of polysaccharides have followed different approaches (Efthimiadou et al. 2014):

       Association with synthetic biopolymers.

       Surface coating of micro‐ or nanosphere polysaccharides with biocompatible synthetic polymers.

       Cross‐linking with different types of reagents.

       Increased hydrophobicity via alkylation reactions.

      The main modification reactions that can be performed on polysaccharides are methylation, acetylation, phosphorylation, silylation, sulfation, carboxymethylation, and amination (Huang et al. 2016). Some studies described the conjugation of polysaccharides with molecules of low molar weight and some active ingredients. The so‐called derivatization of polysaccharides is an important strategy to improve the physicochemical properties of the materials and to introduce them into microbial and tumor cells (“Trojan horses”).

The monographs reported by Huang et al. (2016), Adhikari and Yadav (2018), and Gorgieva (2020) describe examples of derivatization of some microbial polysaccharides for medical and other applications. 2‐phenylhydrazine or hydrazine thiosemicarbazone chitosan, chitosan–metal complexes (chitosan–Cu [II] and chitosan salicylaldehyde Schiff base–Zn [II] complexes), carboxymethyl chitosan, chitosan–thymine conjugate, sulfated chitosan and sulfated benzaldehyde chitosan, glycol‐chitosan and N‐succnyl chitosan, furanoallocolchicinoid chitosan conjugates and polypyrrole chitosan present antitumoral activity. These chitosan derivatives can act inducing apoptosis of tumor cells, affecting the cycle of tumor cells, enhancing the antioxidant activity of organism, activating the body's immune response and inhibiting the tumor angiogenesis. The chemical modifications of bacterial cellulose include oxidation, etherification, esterification, carbamation, and amidation reactions, all resulting in the formation of reactive functional and charged groups, such as sulfate, carboxyl, aldehyde, phosphate, amino, and thiol groups. Among all, the acetylated bacterial cellulose attracts significant interest as noncytotoxic material for cosmetic products, disinfectants, as well as a platform for further coupling (e.g. with drugs and other bioactives), for use in drug delivery. The studies