**6. Polymers**

Biopolymers such as lipopolysaccharides (LPSs), EP and extracellular polymeric substances (EPSs) are high-molecular weight substances secreted by microorganisms [89]. In the case of EP, their antitumor properties have been observed in some bacteria as well as in endophytic fungi. EPSs are exopolymers, constituted by polysaccharides, lipids, proteins and nucleic acids; the composition provides these biopolymers unique properties that can be manipulated for a variety of technological applications [90].

LPSs from Gram negative bacteria possess a lipid moiety and a glucosamine fraction with phosphate groups to improve membrane stability [91, 92]. Some of these LPSs have been studied as flocculating and emulsifying agents; for example, the one produced by *Trichosporon mycotoxinivorans* at a concentration of 8.6 mg/mL was able to flocculate kaolin and charcoal with 80 and 78% of efficiency respectively, while the emulsifying activity by mixing water and kerosene presented an emulsification efficiency of 81% [93].

Another application of LPSs is to enhance the immune response by accelerating the maturation of dendritic cells using immobilized LPS nanostructures; compared to LPS solutions and LPS monolayers, such structures could be useful in HIV patients [94]. In a similar manner, inactivated LPSs from non-sulfur photosynthetic bacteria have been used to stimulate immune response [95].

EPs have become important in material science, being useful as storage molecules, protective capsular layers and as matrix components of biofilms due to their water-binding capacity because of hydroxyl and carboxyl groups. EPs can be used in drug delivery, enzyme immobilization, tissue engineering, among other uses [96], their production depends on composition and growth conditions applied on the culture media [97].

EPs from lactic acid bacteria have been used as emulsifiers and viscosifiers because of their pseudoplastic rheological behavior; the sugar identified have been dextran, reuteran, levan and insulin, pullulan (homopolysaccharides), kefiran and hyaluronic acid (heteropolysaccharides) among others depending on the strain used to produce EP [98, 99].

An example of this kind of EP is levan produced by *Bacillus licheniformis* reported by [100] where the authors studied its physicochemical properties and concluded its utility in stabilizing topical formulations. Other uses that have been studied of levan but from *Halomonas smyrnensis* were on tissue engineering and prosthetics [101].

Hyaluronic acid from *Streptococcus equi* was compared against kefiran isolated from kefir grains (also produced on lactic acid bacteria) demonstrating antioxidant and immunostimulatory activities [102].

Marine EPs are mainly heteropolysaccharides composed of pentoses, hexoses, aminosugars or uronic acids [103]. The EPs of *Pantoea* sp. [97] presented wound healing activity by facilitating cell migration on fibroblasts. The EPs of *Bacterium polaribacter* increased 1.42-fold the wound closure at an EP concentration of 1 mg/mL.

EPS in microbial cells aids in the fixation to marine surfaces, thus forming biofilm communities though a three-dimensional arrangement in which the cells can localize extracellular activities and conduct agonist/antagonist interactions. In marine bacteria, EPSs generally contain higher levels of glucuronic and galacturonic acids. Among the sugars found on EPSs are glucose, galactose, mannose, fructose, rhamnose, uronic acids, N-acetyl-glucosamine and N-acetyl-galactosamine; the protein moiety can occur as peptides, aminosugars, glycoproteins, proteoglycans and amyloid proteins. Proteins can occur as peptides, aminosugars, glycoproteins, proteoglycans and amyloid proteins. Extracellular DNA and extracellular nucleases can be found, thus influencing on the physical consistency [90].

EPS production depend on the presence of divalent cations [90], as it is in the case of *Bacillus vallismortis;* which EPS was better in composition in the presence of zinc enhancing the adsorption capacity [104]; while in the presence of the ferric ion the EPS production is limited [90].

An application of EPS is in microencapsulation of vitamins to formulate functional foods as demonstrated on *Cyanoteche* sp. The authors extracted its EPSs and made encapsulation tests of vitamin B12 either alone or in the presence of arabic gum by spray-drying technique. EPS alone presented a particle diameter of 8 μm and when combined with arabic gum the particle diameter was smaller than that of EPS alone; both microcapsules presented different release kinetics due to the different swelling mechanisms of the EPS [105]. EPS from another *Cyanoteche* strain was found to be useful for controlled delivery of small molecules such as procainamide as well as proteins. The authors found out that adding bivalent cations such as Ca2+, as well as considering the protein charge, the release kinetics could improve [106].

Other encapsulation studies were performed on the EPSs of *Bacillus subtilis* in the preservation of *Lactobacillus plantarum* as probiotic, facilitating its survival in gastric conditions during co-cultivation of both strains [107].

EPSs have been widely used in sludge treatment for pharmaceutically active ingredients removal such as ciprofloxacin as well as sulfonamides. EPS from *Klebsiella* sp. was tested against sulfonamides; the high protein content of EPS (mainly tryptophan and tyrosine) is a critical factor in the adsorption of sulfonamides for hydrophobic interactions with sulfonamides [108]. The same thing happens with ciprofloxacin being important to reach the isoelectric point of the protein moiety as well as the use of iron salts to enhance the adsorption of ciprofloxacin [109–111].

The latter ability of EPSs to adsorb antibiotics needs further studies in order to model and improve the kinetics of controlled release dosage forms giving us a natural and possible biocompatible alternative material for design of molecular pharmaceutical forms.
