**2.1 Biodegradation and biocompatibility of aliphatic polyesters**

The ester linkages of aliphatic polyesters are sensitive to hydrolytic attacks in aqueous media. The water molecules break down the long polymer chains into small molecules with increased water solubility. Alternatively, aliphatic polyesters degraded via enzymatic hydrolysis have been reported. Esterase and lipase are important hydrolytic enzymes that can cleave the internal ester bonds of these polyesters. In addition to both of these enzymes, proteases can degrade the members of the poly(α-hydroxy acid) family as a result of the α-ester linkages in their backbone [14]. These degradation products (i.e., PLA, PGA, and PLGA) can enter the Krebs cycle and be eliminated from the body as carbon dioxide (CO2) and water, resulting in the high biocompatibility of aliphatic polyesters [12]. **Figure 2** shows the biodegradation mechanism in which these polyesters are converted into carbon dioxide and water.

The hydrolysis of polyesters happens in three stages. During the first stage, water is absorbed onto the exterior surface and matrix swelling and polymer chain transfer occur. This absorption results from the hydrophobic properties of aliphatic polyesters and leads to surface erosion. In the next stage, an amorphous region becomes swollen followed by stress relaxation of the polymer chain [6]. Next, the matrix can absorb additional water molecules via a diffusion mechanism that leads to the hydrolysis of the polymeric chains in the matrix, creating matrix porosity. After the final stage, the hydrolysis products are acid derivatives (R▬COOH), which are catalyzed by acids that trigger polyester hydrolysis. The parent derivatives can cause dissociation of the carboxyl end groups into their conjugate carboxylate anions (R▬COO− ) also forming the acidic proton (H+ ) byproducts. The acid produced catalyzes the hydrolytic reaction, generating additional acid. Continuous mass loss occurs via the formation of these fresh acids, resulting in the autocatalytic degradation of the polyester. Moreover, the addition of acidic compounds (i.e., drugs or additives) and environmental pH can modify the rate of polymer degradation for catalytic hydrolysis [15, 16].

An example of the above process is that of PLGA degradation. Synthesized PLGA has two different structures, as it can be acid-terminated or ester-terminated. Acid-terminated PLGA and ester-terminated PLGA have end-group structures of carboxylic acids (PLGA▬COOH) and esters (PLGA▬COOCH3), respectively. End group functionalization causes differences in PLGA biodegradation.

**Figure 2.** *Hydrolytic degradation of aliphatic polyesters.*

*Aliphatic Polyester Nanoparticles for Drug Delivery Systems DOI: http://dx.doi.org/10.5772/intechopen.100977*

Acid-terminated PLGA is degraded rapidly in comparison with the more hydrophobic ester-terminated PLGA. Carboxylic end-capped PLGA can be used as an acid to initiate autocatalytic degradation; thus, these acids have been applied to catalyze acid hydrolysis and promote autocatalytic degradation. Therefore, acid-terminated PLGA hydrolyzes the ester linkages more easily than ester-terminated PLGA as a result of the carboxylic end groups that are capable of producing acidic byproducts, as shown in **Figure 3** [17].

Furthermore, the rate of degradation of PLGA is dependent on the PDLLA:PGA ratio as determined by the weight percentages of PDLLA and PGA, such as 50:50, 65:35, 75:25, and 95:5. The decelerated degradation of PLGA occurs at a high amount of PDLLA, whereas a higher amount of PGA indicates rapid degradation. PDLLA, with methyl groups in its structure, has reduced chain mobility (chain configuration), leading to more hydrophobicity than PGA, which is devoid of these methyl groups (**Figure 1**). PGA is a highly hydrophilic polymer that can absorb more water molecules [6, 13]. Thus, PGA hydrolysis is more complimentary than PDLLA hydrolysis. As a rule, the drug release of PLGA is affected by the biodegradation of PDLLA and PGA. A 50:50 ratio of PDLLA:PGA has been shown to prompt degradation and produce higher rates of drug release [18, 19].

#### **2.2 The properties of aliphatic polyesters properties in delivery systems**

Following an earlier example, these differences in chemical structure illustrate how the changes in the physicochemical properties of the polymers are linked to the drug release rate via aliphatic polyester biodegradation. The biodegradation characteristics are controlled by polymer crystallinity, glass transition temperature (Tg), polymer hydrophobicity, and molecular weight (MW), all of which influence hydrolysis.

#### *2.2.1 Polymer crystallinity*

The crystalline regions of polymers consist of regular and orderly arranged polymeric chains that result in nanoparticles with high drug-loading abilities. Highly crystalline polymers present difficult mass transfer of both water and drug molecules. Water molecules are strongly absorbed and restricted within the

**Figure 3.**

*Proposed hydrolysis reactions of acid-terminated PLGA (a) and ester-terminated PLGA (b) by autocatalytic degradation.*

orderly polymeric chains of the crystalline regions, leading to a lower swelling rate. Crystalline polymer regions are resistant to hydrolysis compared to amorphous regions [16, 20]. As a result, the crystalline regions display delayed degradation. The byproducts of later hydrolysis still contain a very large number of high MW compounds in the polymer in the matrix, resulting in a high degree of chain entanglement. Polymer chain entanglement has an important effect on the drug release rate. High amounts of entanglement cause the drug release rate to be slower than that of highly disordered amorphous polymer materials.
