**1. Introduction**

Modern packaging should protect products from external factors, extend the period of maintaining the quality of the product and above all, minimize impact on the environment [1–6]. Figure 1 summarizes some of the properties desired in common packaging materials. Detailed properties have been discussed in some excellent review articles, so we won't be going into more detail [1,2,7–9]. In this direction, public awareness is rapidly growing and attracting greater attention to ecology, as well as the use of natural substances for a range of applications from automotive to biomedical [10–16]. A tendency in the packaging industry to design innovative materials and introduce new solutions is gaining greater attention [17,18]. Active and modern packaging frequently relies on natural substances

such as natural polysaccharides [9]. It is imperative to preserve all aspects of environmental safety during production, as well as the effectiveness and safety of use for patients [19–23]. Interestingly, the cyclic olefin copolymer (COC) is most commonly used for tamper-resistant packaging and is a remarkable alternative to a damped polyvinyl chloride (PVC).

**Figure 1.** General properties of commonly used packaging materials.

Packaging in medical and biomedical engineering is defined as a technique that enables the closure of a pharmaceutical product from its production to its end use [24]. The role of pharmaceutical packaging is to provide life-saving drugs, surgical devices, nutraceuticals, pills, powders and liquids, to name a few [7,25]. Pharmaceutical packaging influences the isolation and ensures the safety, identity and convenience of using the drug. The packaging must communicate well with the patient so that there are no adverse effects on the health of the patient. The key issue in packaging is also the issue of ecological safety [26,27]. Drug companies that pack drugs are among the industry leaders due to their technological advances. Current trends in industrial research on such new materials are the result of a continuous series of challenges being faced by the industry. The packaging industry is constantly evolving and is an important factor in the development of the pharmaceutical industry and biomedical sciences. Electrospinning of polymers/nanomaterials [28,29] is one of the potential methods in the packaging process that allows for the use of biopolymers [30]/natural substances for the production of medical packaging, dressings, biosensors, medical implants, and is a growing trend in biomedical sciences [10,31–39]. Figure 2 illustrates the schematic of a coaxial electrospinning setup. The inset shows an illustration of a coaxial jet under applied voltage [39]. Mercante et al in their excellent review articles have also shown the number of publications that's involved the use of electrospinning in sensor applications and the number of these publications is increasing day by day [10].

Different types of electrospun fibers are being produced for biomedical applications [32]. However, the electrospinning of biopolymers is a very challenging process. For example, in the case of chitosan, its neutralization lead to the loss of chitosan traits by using unsuitable substances. In the production of continuous filaments, suitable solvents should be used so that there is no interruption. In addition, during chitosan nanofiber synthesis, the value of the electric field generated is also crucial. Too high of an electric field causes repulsion between ionic groups of the polymer backbone, which disturbs the formation of continuous filaments. The use of chitin and chitosan nanofibers in biomedical and other applications has been recently reviewed [32–34]. Jayakumar et al, in their article, had primarily focused on the properties, preparation and biomedical applications [32]. Electrospinning of silk has also been reported [35]. It is used because of beneficial properties such as non-toxicity and biocompatibility. Due to its positive mechanical properties, it can be used in various temperature and humidity ranges. However, in the case of silk, one of the protein components, sericin, should be removed before biological application because it can cause allergic reactions, for example, in the case of medical dressings [36–38].

**Figure 2.** Schematic of coaxial electrospinning setup. The inset shows an illustration of a coaxial jet under applied voltage [39]. Reprinted with permission from Ref. [39]. Copyright American Chemical Society, 2010.

One of the organisms that is produced as a structural component of silk protein is Bombyx mori [40]. The protein it produces, silk fibroin, is a large crystalline macromolecule consisting of repeating units of amino acids, mainly alanine (A), glycine (G) and serine (S). The fibers that are formed with its participation exhibit good mechanical properties [41]. Researchers have also demonstrated that electrospinning of biopolymer blends of chitin and silk fibroin is possible [42]. In this process, nanofibrous membranes of blended chitosan and silk fibroin were successfully prepared using electrospinning in a HFIP/TFA spinning solvent. With the increment in the content of silk fibroin, the typical diameter of the as-prepared nanofibers was found to increase. The incorporation of silk fibroin was also found to contribute to the enhancement in the mechanical properties of nanofibrous membranes. Furthermore, with the increment in the chitosan content, the antibacterial activity became significantly suitable for wound dressings [42]. Electrospun collagen–chitosan nanofiber having a typical fiber diameter of 434–691 nm was also prepared as a biomimetic extracellular matrix (ECM) for endothelial cells and smooth muscle cells [43]. Different characterization techniques such as FTIR spectra analysis, XRD analysis, DSC and tensile testing were carried out to analyse the developed materials [43]. Double-network (DN) agarose/polyacrylamide nanofibers were prepared by electrospinning [44]. The DN of agarose/polyacrylamide (PAAm) nano fibers developed using simultaneous photo-polymerization and electrospinning. Different characterization techniques were used to confirm the realization of a crosslinked double-network. In comparison to the pristine agarose, the electrospun fibrous agarose/PAAm demonstrated 66.66% enhancement in the strength [44]. Similarly, electrospinning of alginate is being carried out for a number of applications [45]. Alginate is an important biopolymer with vast potential [46].

### *1.1. Synthetic Polymers*

Different types of polymers ranging from natural to synthetic are rapidly becoming the most interesting subject of research in the sector of the biomedical industry [47]. They are often used in the packaging of medicines [48,49], as well as in the development of flexible ampoule/syringes that are more easy to use. However, adsorption and migration of the bioactive substance to the polymer changes in pH, permeability of oxygen, optical properties and the release of leached components affect their use and should be taken into account [50,51]. Interaction of the different outer components not only affects the drug but also the function of the polymeric container. Polyolefins, high-density polyethylene (HDPE) or polypropylene (PP) are some of the most common polymers used for the production of vials. Often, multilayer containers are developed to achieve such requirements as inertia, oxygen or UV protection. Polycyclic and olefinic polymers and copolymers (Daikyo Crystal Zeniths) have been used for filling polymer syringes [51,52]. Devices such as PVC tubes containing di-2- ethylhexylphthalate (DEHP) plasticizer are used in dialysis for blood supply or extracorporeal oxygenation. The bags containing the polymer are used to donate blood and store blood products. Due to lipophilicity, the plasticizer is transferred from the polymer surface to lipids and red blood cell membranes [53]. It has been found that the plasticizer in blood bags reduces haemolysis of red blood cells by about 50% compared to blood stored in non-plastic containers, which improves the quality of the blood product [50]. Tubes for extracorporeal circulation are often heparinized to reduce the coagulation, which causes intense contact with PVC and increases thrombogenicity [54].

For the storage of red blood cells, an alternative plasticizer such as butyryl-trihexyl-citrate (BTHC) or di-iso-nonyl-1, 2-cyclohexanedicarboxylate (DINCH) is used. Polyolefins as alternative polymers are used to store platelets [55,56]. Polyethylene and polyurethanes are used to create tubes. Tubes of positronic pumps are usually made of silicone [51]. Hemodialysis membranes are produced as bundles of hollow fibers with a surface in contact with blood. The technical requirements concern mainly the permeability for substances smaller than albumin, preventing the passage of impurities from the dialysate to the blood, and the compatibility of the membrane with blood. Previously, dialysis membranes were made of cellulose [51,57]. The hydroxyl groups were replaced with acetylene derivatives or other modified additives, preventing the activation of the complement system and the associated leukocyte activation and leukocyte sequestration in the lungs [51,57]. Synthetic membranes consist of a hydrophobic base material and hydrophilic components. The polyaryl sulfone co-precipitation membranes, polysulfone (PSf) and polyvinylprolidone (PVP) membranes are the most popular for a number of applications [58]. In addition, other membrane materials such as polyamide (PA), polycarbonate (PC) and polyacrylonitrile (PAN), PMMA, polyester polymer alloy (PEPA), ethylene vinyl alcohol copolymer (EVAL), and molecular thin nanoporous silicon diaphragms are also used. Poly (ethylene glycol) (PEG) is used in membranes to improve compatibility with blood [59]. Polymer stents used in the upper sections of the ureter are designed to overcome the problems of sperm infection. Silicone is the best biocompatible material with the lowest incrustation tendency. Its use is limited by low mechanical stiffness and high resistance. Therefore, polyurethane products with better mechanical properties than silicone were optimized [51,60]. The stents were coated with glycosaminoglycans (GAGs, heparin or pentosan polysulfone), phosphorylcholine, which increases the comfort of patients, reduces bacterial colonization and encrustation [51,60].

#### *1.2. Biopolymers: Structure of Alginate*

Recently, there has been a great thrust on the usage of biopolymers for a number of applications, especially in the biomedical and pharmaceutical [61–65]. The functional efficiency of the biopolymer molecules depends on the composition, physicochemical properties and structural features [66–68]. It is possible to rationally design the composition and structure of the biopolymer to obtain the appropriate functional attributes [23]. The internal structure of the polymer molecule determines many functional characteristics such as permeability, chargeability and integrity [69]. The stability of the biopolymer particles and their ability to aggregate is influenced by the electrical characteristics. Biopolymer

particles with a high electric charge will repel and prevent aggregation. Molecules of biopolymers and their electrical properties influence the interaction with other molecules present in the surrounding environment [69]. Among natural biopolymers, alginate is one of the most popular and intensely studied [70,71]. It is an anionic biopolymer consisting of units of mannuronic acid and guluronic acid in irregular blocks [72]. Mannuronic acid and guluronic acid are linked by glycosidic linkages [73–75]. Mannuronic acid forms β (1 → 4) bonds and α bonds (1 → 4) with guluronic acid [76]. The stiffness of molecular chains is ensured by the rigid and bent conformations of guluronic acid [77,78]. Hadas and Simcha have recently reported their interesting work on the characterization of sodium alginate and calcium alginate with particular emphasis on their structure [79]. Different properties and applications of alginate have also been reviewed [80]. The properties of alginates used in biomedicine can be shaped by modifying the availability of their hydroxyl and carboxyl groups [81]. It affects the properties of alginates, such as solubility, hydrophobicity and their biological activity. Alginate hydrogels were created by crosslinking polymer chains [82]. The chemical properties of alginate hydrogels were found to depend on the cross-linking density of the chain [83]. One of the methods used in the design of alginate hydrogels is intermolecular cross-linking, in which only the alginate guluron groups react with the divalent cation most often the calcium used to gel the alginate [84]. Marguerite has summarized the applications of alginate especially for packaging in an excellent review article, so we won't go into detail [85].
