**3.2. Drug delivery**

Drug delivery area involves an art of transporting drugs or therapeutic compounds to human body. It is a critical research field where the transported compounds must achieve the optimum therapeutic effect to protect or heal from any kind of disease. The use of polysaccharide materials in drug delivery systems is increasing mainly because of their ability to form hydrogel with stimuli‐responsive properties [51, 52]. Besides being mechanically deficient, polysaccharide‐based drug carrier normally have initial burst problem in the delivery system. Therefore, controlled delivery systems were proposed by addition of various fillers into polysaccharide matrix. This includes incorporation of Fe3O4 [53], CaCO3 [54], silica nanopar‐ ticle [55], graphene oxide [56], gold nanoparticle [57], and montmorillonite [58].

Oral drug administration is one of the preferred routes since it is convenient and has no cross‐ infection. However, drugs taken through oral route have to pass through different phases of gastrointestinal tract, where pH values vary greatly. The change in pH may lead to loss of mechanical strength and fast degradation. To protect the drugs from the harsh environment in stomach before they can be absorbed in the intestine, pH‐sensitive polysaccharide compo‐ sites were developed. Protein drugs were encapsulated in inorganic carrier [59, 60] and gel beads [61, 62] to prolong their release. Series of pH‐sensitive composite hydrogel composites of alginate and chitosan base were prepared with addition of attapulgite [61], bone ash [63], and other polymer‐like pectin [64] that clearly showed their release dependence to pH condition. It was found that cross‐ linking and nanofiller loading can significantly improve the targeted release [65, 66] in the pH‐sensitive polysaccharide composites.

Polysaccharides like starch and carrageenan are thermoresponsive polymers. They can be utilized in drug delivery with thermal sensitivity. ?‐carrageenans were incorporated with Au [67] and silica [68] nanoparticles. The effect of both nanoparticles on the microstructure and strength of the hydrogel had implications in the mechanism of controlled release as demon‐ strated by *in vitro* release studies using a drug model and displayed potential for thermally controlled drug delivery. Schmitt et al. loaded aqueous drug containing 5‐aminosalycylic acid (5‐ASA) into halloysite nanotubes and dispersed them well in thermoplastic starch matrix [69]. The swelling of the produced nanocomposite strongly depends on the temperature but not on pH. Furthermore, ?‐carrageenans were also studied for a triple‐response hydrogel by simul‐ taneous formation of super paramagnetic iron oxide nanoparticles (SPION) and crosslinking of of polyacrylyc acid (PAA) [70]. The swelling capacity and drug release of ?‐carrageenan‐ PAA/SPION hydrogel were tested to different temperature, pH, and magnetic field to assess the sensitivity of the hydrogel. They have successfully synthesized biocompatible hydrogel with considerable temperature, pH, and external magnetic field sensitivity using simple and convenient one‐pot strategy. Another interesting functional hydrogel of ?‐carrageenan was prepared by reinforcing with multiwalled carbon nanotubes (MWCNT) [71]. This hydrogel composite shows increased release of a model drug in *in vitro* conditions due to the near‐ infrared (NIR) photothermal effect of MWCNTs, thus demonstrating its promising role as carrier for remotely activated drug delivery.

Apart from being too focused on the additional function on drug carrier material, exci‐ pients must have the ability to encapsulate and protect the drugs. Some drugs have some specific needs to achieve targeted release. Targeted release is very important to ensure op‐ timum drug effects. Aceclofenac is an orally administered phenyl acetic acid derivative with effects on a variety of inflammatory mediators. Its frequent administration and pro‐ long treatment was associated with various side effects. The use of *Boswellia* gum resin into chitosan polymer to deliver nonsteroidal antiinflammatory drug has caused signifi‐ cant improvement in drug entrapment efficiency (~40%) of the polymer composites [72]. Highly hydrophobic drug like curcumin frequently has poor solubility in polysaccharide excipients. An attempt to add pluronic F127 into alginate/chitosan matrix found to have increased the encapsulation efficiency of curcumin inside the composite, indicating better dispersion of curcumin inside matrix [73]. Local avascular delivery to treat orthopedic in‐ fections caused by Methicillin‐resistant *Staphylococus aureus* (MRSA) was developed by fabrication of porous chitosan/bioceramic β‐tricalcium phosphate (CS/β‐TCP) [74]. The composite was then coated with poly(?‐caprolactone) (PCL) to retard the release of vanco‐ mycin for 6 weeks at levels to inhibit MRSA proliferation. Recently, the potential applica‐ tion of deferoxamine (DFO) in several iron dysregulation diseases has been highlighted. However, DFO presents significant limitations in clinical use due to its poor absorption in the gut and very short plasma half‐life. Inclusion of poly(D,L‐lactide‐co‐glycolide) micro‐ spheres into preformed chitosan/alginate hydrogel provided strong DFO entrapment in the hydrogel network and slow release [75].

#### **3.3. Packaging films**

The disability of conventional plastic material used in packaging to biodegrade has led to serious solid waste problem. Polysaccharide materials are fully recognized as potential alternative for petroleum‐based plastics, mainly contributed by its biodegradability and environmental friendly properties. Packaging basically functions as container and external preserver or protector to consumer goods including food. Materials used in packaging need to possess excellent mechanical properties and barrier properties so they will be able to maintain the condition for the products to extend their shelf‐life. Therefore, several reinforce‐ ments have been identified to be good fillers for polysaccharide films.

controlled drug delivery. Schmitt et al. loaded aqueous drug containing 5‐aminosalycylic acid (5‐ASA) into halloysite nanotubes and dispersed them well in thermoplastic starch matrix [69]. The swelling of the produced nanocomposite strongly depends on the temperature but not on pH. Furthermore, ?‐carrageenans were also studied for a triple‐response hydrogel by simul‐ taneous formation of super paramagnetic iron oxide nanoparticles (SPION) and crosslinking of of polyacrylyc acid (PAA) [70]. The swelling capacity and drug release of ?‐carrageenan‐ PAA/SPION hydrogel were tested to different temperature, pH, and magnetic field to assess the sensitivity of the hydrogel. They have successfully synthesized biocompatible hydrogel with considerable temperature, pH, and external magnetic field sensitivity using simple and convenient one‐pot strategy. Another interesting functional hydrogel of ?‐carrageenan was prepared by reinforcing with multiwalled carbon nanotubes (MWCNT) [71]. This hydrogel composite shows increased release of a model drug in *in vitro* conditions due to the near‐ infrared (NIR) photothermal effect of MWCNTs, thus demonstrating its promising role as

Apart from being too focused on the additional function on drug carrier material, exci‐ pients must have the ability to encapsulate and protect the drugs. Some drugs have some specific needs to achieve targeted release. Targeted release is very important to ensure op‐ timum drug effects. Aceclofenac is an orally administered phenyl acetic acid derivative with effects on a variety of inflammatory mediators. Its frequent administration and pro‐ long treatment was associated with various side effects. The use of *Boswellia* gum resin into chitosan polymer to deliver nonsteroidal antiinflammatory drug has caused signifi‐ cant improvement in drug entrapment efficiency (~40%) of the polymer composites [72]. Highly hydrophobic drug like curcumin frequently has poor solubility in polysaccharide excipients. An attempt to add pluronic F127 into alginate/chitosan matrix found to have increased the encapsulation efficiency of curcumin inside the composite, indicating better dispersion of curcumin inside matrix [73]. Local avascular delivery to treat orthopedic in‐ fections caused by Methicillin‐resistant *Staphylococus aureus* (MRSA) was developed by fabrication of porous chitosan/bioceramic β‐tricalcium phosphate (CS/β‐TCP) [74]. The composite was then coated with poly(?‐caprolactone) (PCL) to retard the release of vanco‐ mycin for 6 weeks at levels to inhibit MRSA proliferation. Recently, the potential applica‐ tion of deferoxamine (DFO) in several iron dysregulation diseases has been highlighted. However, DFO presents significant limitations in clinical use due to its poor absorption in the gut and very short plasma half‐life. Inclusion of poly(D,L‐lactide‐co‐glycolide) micro‐ spheres into preformed chitosan/alginate hydrogel provided strong DFO entrapment in

The disability of conventional plastic material used in packaging to biodegrade has led to serious solid waste problem. Polysaccharide materials are fully recognized as potential alternative for petroleum‐based plastics, mainly contributed by its biodegradability and environmental friendly properties. Packaging basically functions as container and external preserver or protector to consumer goods including food. Materials used in packaging need

carrier for remotely activated drug delivery.

74 Composites from Renewable and Sustainable Materials

the hydrogel network and slow release [75].

**3.3. Packaging films**

Clay minerals have received extensive study as reinforcing filler in polysaccharide‐based packaging film and coating [76]. Nanoclays have been a subject of interest nowadays con‐ sidering their high aspect ratio and surface area, alongside with biocompatibility feature. The inclusion of clays showed good dispersion in polysaccharide matrix and resulted in superior mechanical and barrier properties. Incorporation of montmorillonite (MMT) nanoclay into alginate film has shown increase in tensile strength of up to 36% [77]. MMT may also enhance the thermal stability, storage modulus, and barrier properties of chito‐ san [78]. A comparative study of nanobiocomposite of carrageenan/zein and carrageenan/ mica found mica clay to be more efficient as an additive to carrageenan for clay has better dispersion in carrageenan composite [79]. Cellulose nanocomposite foam containing MMT was investigated as a substitution for synthetic polymer foam trays. The presence of nano‐ clay caused more uniformity in the structure of the foam, thus resulted in higher com‐ pressive strength, Young's modulus, and density [80]. The use of sepiolite and palygorskite fibrous clays in some polysaccharides of different types was reported [81]. The good compatibility between these fibrous clays with the polymers resulted in im‐ proved mechanical properties, barrier to UV light, stability in water, and reduction of wa‐ ter absorption, which make them very attractive bionanocomposite in the food packaging sector. Other fillers included into polysaccharide‐based packaging films are nanosilica [82], zinc oxide [83], and copper [84] nanoparticles.

In terms of polysaccharide composites, certain fillers were added to the packaging films not only to improve their mechanical and barrier properties, but special characteristics can also be instilled for the production of active packaging films. Active packaging refers to the packaging systems used for products like foods and pharmaceuticals that have extra function to extend their shelf‐life, in addition to the general purpose of providing external protective barrier. Introduction of different kinds of natural and synthetic antimicrobial agents into packaging have been studied against various pathogens such as *Listeria mono‐ cytogenes*, *Escherichia coli*, *Clostridium perfringens*, *Staphylococcus aureus*, *Salmonella pullorum*, *Bacillus cereus*, and *Pseudomonas aeruginosa*. The inhibitory effect of the films was deter‐ mined by measuring the bacterial growth inhibition zones. Preparation of polysaccharide‐ based packaging films with incorporation of nanometals, organically modified clay minerals, plant essential oils and extracts, and other natural antibacterial agent were test‐ ed for their antimicrobial properties.

Clays are organically modified to increase their hydrophobicity since the polysaccharide matrix is already water sensitive and has low water vapor barrier properties. They also exhibit biocompatibility, bioactivity, and can be used as antibacterial materials. The inclusion of modified clay Cloisite 30B in carrageenan/locust bean gum matrix [85] and zeolite‐A inside chitosan matrix [86] have demonstrated high antimicrobial efficiency compared to neat polysaccharide. A combination of halloysite nanotube and nisin had been expected synergistic effect in active packaging [87]. Nisin is an antimicrobial agent recognized to fight against *Listeria* and spores of *Bacilli* and *Clostridia*. However, a study by Lu et al. showed the formation of 3% alginate solution containing nisin‐ethylenediaminetetraacetic acid (EDTA) might have limited the release of nisin [88]. Lower concentration of alginate was proposed to see the effect of alginate concentration to nisin performance. Another study included silver (Ag) nanopar‐ ticles combined with Cloisite 30B in ?‐carrageenan as antimicrobial bionanocomposite films [89]. Ag nanoparticles have attracted considerable attention for packaging application for their antibacterial activities, high thermal stability, and low toxicity. Ag/clay mineral was prepared to overcome the tendency of Ag nanoparticles to agglomerate when used alone. While organically modified nanoclay exhibited strong antibacterial activity against Gram‐positive bacteria, Ag nanoparticles exhibited strong antimicrobial activity against Gram‐negative bacteria. Thus, the combination of these two antibacterial agents helps in providing polymer packaging with strong antimicrobial properties. Shankar et al. investigated different types of Ag particles incorporated into alginate‐based films [90]. They found Ag zeolite and citrate reduced Ag nanoparticles provide better antimicrobial activity than metallic silver and laser‐ ablated Ag nanoparticles in alginate compared to the neat films.

Strong antimicrobial activities can also be induced inside packaging films by plant ex‐ tracts and essential oils. Extracts of green and black tea were added into chitosan dis‐ played good antioxidant and antimicrobial capacity [91]. Natural extract from the seeds, pulps, and peel of grapefruit was also put inside carrageenan film to encourage the anti‐ bacterial, antifungal, and antioxidant properties [92]. However, addition of plant extracts showed decreased tensile strength and elongation at break of the packaging films. In ad‐ dition, oregano, thyme, and *Satureja hortensis* essential oils were used in carrageenan films to overcome the poor water vapor barrier and as possible substitutes for synthetic antioxi‐ dant‐antimicrobial agents to achieve oxidative and microbial stability [93, 94]. The tensile strength was lowered with increasing essential oil concentration. They suggested it hap‐ pened because of the replacement of strong polymer‐polymer interaction with oil‐polymer interaction in the film network.
