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

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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 of Zayed et al. (2017) and Tao et al. (2018) described the use of other modified microbial biopolymers to serve as carriers for antimicrobial and antitumoral drugs.

Table 2.2 Antitumoral nanoparticles (NPs), nanofibers and nanofilms/antimicrobial nanoparticles (NPs), nanofibers and nanofilms/tissue engineered nanofibers and nanofilms.

Nanomaterials Actions References
Bicalutamide folate conjugated‐chitosan functionalized PLGA NPs NPs presented potential action against prostate cancer Dhas et al. (2015)
Tumor‐targeting delivery system of paclitaxel by PEGylated O‐carboxymethyl‐chitosan NPs grafted with cyclic Arg‐Gly‐Asp peptide NPs presented potential action against Lewis lung carcinoma Lv et al. (2012)
PEGylated chitosan nanocapsules conjugated to a monoclonal antibody anti‐TMEFF‐2 targeted delivery of docetaxel Nanocapsules presented potential action against non‐small cell lung carcinoma Torrecilla et al. (2013)
Doxorubicin hyaluronic acid block copolymers NPs NPs used as a self‐targeting drug delivery in overexpressed CD44 glycoprotein cells of breast cancer Nitta and Numata (2013)
Indocyanine green‐Levan NPs Self‐assembled indocyanine green‐Levan NPs used for targeted breast cancer imaging Kim et al. (2015)
Doxorubicin‐carboxymethyl xanthan gum‐capped gold NPs NPs showed in vitro efficacy against glioblastoma cells Alle et al. (2019)
Doxorubicin‐loaded alginic acid/poly[2‐(diethylamino)ethyl methacrylate] NPs NPs exhibited greater in vivo antitumoral activity compared to free doxorubicin Cheng et al. (2012)
Cationized dextran and pullulan modified with diethyl aminoethyl methacrylate (DEAEM) Positively charged nanocomplexes with DNA and they are cytocompatible in C6, HeLa and L929 cells. Transfection efficiency of the vectors was evaluated using p53 plasmid, which demonstrated good transfection in isolated cancer cells (C6 and HeLa) Sherly et al. (2020)
Alginate nanogel encapsulating Artemisia ciniformis extract Nanogels loaded with A. ciniformis extract inhibited cell proliferation and arrested the cell cycle at the G0/G1 phase. Induction of apoptosis occurred in a time‐ and dose‐dependent manner; expression levels of pro‐apoptotic genes were up‐regulated; down‐regulation of anti‐apoptotic and metastatic genes were detected; nanogels exhibited potent anticancer activity against AGS gastric cancer cells Rahimivand et al. (2020)
Bacterial cellulose + Fe3O4 NPs Magnetic materials made from tetraaza macrocyclic Schiff base bacterial cellulose ligands with magnetite nanoparticles (Fe3O4 NPs) effectively inhibited the growth of the CT26 tumor models in BALB/c mice Chaabane et al. (2020)
Clindamycin phosphate‐xanthan gum‐ZnO NPs NPs applied as topical anti‐inflammatory drug carrier for acne treatment Karakuş (2019)
Chitin Silver NPs associated with chitin/Ag nanofibers presented strong antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Influenza A virus Park and Kim (2015)
Polycaprolactone(PCL)/gelatin + terbinafine hydrochloride (TFH) Nanofibers presented antifungal activity against Trichophyton mentagrophytes, Aspergillus fumigatus and Candida albicans Paskiabi et al. (2017)
Chitosan + gentamicin loaded liposome Liposome presented antibacterial activity against E. coli, P. aeruginosa and Staphylococcus aureus Monteiro et al. (2015)
Chitosan (CS)/poly(vinyl alcohol) (PVA) + silver nanoparticles CS/PVA nanofibers containing Ag NPs showed high antibacterial activity against E. coli Nguyen et al. (2011)
Poly(D,L‐lactic acid‐co‐glycolic acid) (PLGA) + fusidic acid (FA) and rifampicin (RIF) nanofibers Dual‐loaded nanofibers exhibited in vitro antimicrobial activity against two strains of methicillin‐resistant S. aureus (MRSA) and Staphylococcus epidermidis Rho et al. (2006)
Zinc ions (Zn2+)‐loaded 2,2,6,6‐tetramethylpiperidine‐1‐oxyl oxidized bacterial cellulose (TOBC) nanofiber‐reinforced biomimetic calcium alginate hydrogel Calcium alginate/TOBC biomimetic hydrogels loaded with Zn2+ exhibited good mechanical, antimicrobial, and biological properties at Zn2+ concentration of 0.0001 wt%. Zhang et al. (2019)
Polyhydroxybutyrate/poly(butyleneadipate‐co‐terephthalate) (PHB/PBAT)‐based biodegradable antibacterial hydrophobic nanofibrous membranes Nanofibrous membranes were tested against E. coli and S. aureus and presented good antimicrobial activity with 6.08 and 5.78 log reduction, respectively Lin et al. (2017)
Chitosan nanofiber Biocompatible chitosan nanofiber membranes used for bone regeneration in rabbit calvarial defects with healing effect and no evidence of inflammatory reaction Shin et al. (2005)
Collagen/elastin nanofibers Nanofibers coated with ECM proteins with good potential for wound dressing and scaffolds for tissue engineering Rho et al. (2006)
Poly (L‐lactide‐co‐glycolide) (PLGA)/chitin nanofibers Biodegradable electrospun nanofibers of PLGA and chitin presented cell adhesion and spreading for normal human keratinocytes, and were good matrices for normal human fibroblasts Min et al. (2004)
Poly (L‐lactide‐co‐glycolide) (PLGA)/dextran nanofibers Nanofibers based on blends of dextran and PLGA were tested in terms of interaction with dermal fibroblasts considering cell viability, proliferation, attachment, migration, extracellular matrix deposition, and cytoskeleton organization, and the functional gene expressions were characterized, scaffolds with good potential to enhance the healing of chronic or trauma wounds Pan et al. (2006)
Poly(ε‐caprolactone) (PCL)/gelatin + metronidazole Metronidazole was loaded in PCL/gelatine, and a sustained release was observed and significantly prevented anaerobic bacteria colonization; cytocompatibility for drug concentrations up to 30% Xue et al. (2014)
Chitosan‐alginate nanofibers + gentamicin Chitosan‐alginate nanofibers with 1–3% wt gentamicin significantly enhanced skin regeneration in mice model by stimulating the formation of a thicker dermis, increasing collagen deposition, and increasing the formation of new blood vessels and hair follicles Bakhsheshi‐Rad et al. (2019)
Nanotechnology in Medicine

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