2.1.1 Ionic Cross-linking
Cross-linking is the process in which two or more polymer chains are synthetically bonded; the bonds can either be ionic or covalent. The addition of polymers or ions to the original molecule would change its chemical structure, which changes its physical properties. [2]
Alginate is naturally non-degradable in the human body because humans lack alginase, which is the enzyme that can break the bonds in alginate. To address alginate’s non-biodegradability, 12.5 mL of 2% w/v sodium alginate solution was mixed dropwise with 25 mL of 3% w/v calcium chloride solution using a syringe with size-22 needle. Calcium ions displaced the sodium ions, which resulted in calcium alginate beads as the product. Unlike its aqueous reagents, calcium alginate has gel-like properties, which enables therapeutics to be encapsulated in the gel. The calcium alginate beads degrade when the divalent cations, in this case calcium ions, are released during reactions with the surrounding media. [3]
2.1.2 Therapeutic Encapsulation
Therapeutic encapsulation in hydrogel beads allows for transport and release of therapeutics in the human body as the beads transverse down the GI tract. Therapeutics are released from the hydrogel beads over time through the hydrogel’s pores, and when the hydrogel degrades after divalent cations are removed. In this project, antacids were the planned therapeutics, but food coloring was used as a test therapeutic because of its visibility in clear water. After filtering the calcium alginate beads from the calcium chloride solution, the beads were immersed in food coloring and stirred until they were saturated. [3]
An alternative method of loading the calcium alginate beads with therapeutics is to use a gel rotary die from Phase One Machining. The therapeutic and hydrogel are poured into the die simultaneously, and it's configuration and spin allows the hydrogel to harden around the therapeutics. [4]
2.1.3 Polyelectrolyte Multilayering
The problem with calcium alginate beads is that the hydrogel is very porous. Calcium alginate has pores ~0.5-3 mm in diameter, which allows for quick diffusion of encapsulated therapeutics. To address calcium alginate’s porosity, the beads were dried, then coated with chitosan, which has pores ~60-490 um in diameter. [1]
Alginate and chitosan will form a precipitate when mixed because the former is a polyanion, and the later is a polycation. If they form a solid precipitate, it will not retain the properties of a hydrogel. However, the precipitate is a polyelectrolyte complex (PEC), which is the association complex formed between oppositely charged particles. PECs are generally neutral in charge and impermeable. Using that information, a polyelectrolyte complex can be formed in the shape of a thin film to separate the alginate and chitosan from further interaction. To form this film, the anion is quickly (1-2 s) dipped in the cation and washed. Figure 3 illustrates the polyelectrolyte multilayering (PEM) technique. Figure 4 is a diagram of the chitosan alginate beads. [5]
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