**1. Introduction**

Our inspiration for the examples contained within this chapter comes from our direct experience. Chumnanvej et al. retrospectively investigated the clinical outcomes of patients treated after ruptured cerebral arteriovenous malformation (AVM) admitted to Ramathibodi Hospital, Thailand. The results showed that approximately 50% and 7% of cases had symptoms of intracranial hemorrhage and hemorrhage associated with aneurysms, respectively [1]. A subarachnoid hemorrhage (SAH) is a hemorrhage that occurs in the subarachnoid space and leads to rupture. After cerebral surgery, these patients carry the risk of developing vasospasms within 4–14 days after surgery, with the peak occurring at 7 days [2]. Vasospasms can result from a reduction in the rapid release of blood escape from the cerebrum. Nicardipine hydrochloride (NCH) is a calcium channel blocker that is used to treat this vascular condition; nevertheless, the half-life of NCH is approximately 8 h and provides an insufficient dose to treat vasospasms.

From a biomedical engineering point of view, polymers can be employed, particularly in neurosurgery, as surgical sutures, vascular grafts, stents, implants, tissue substitutes, or drug delivery systems. Additionally, these polymers could be biopolymers. Polymers must have the required physical properties and also be biocompatible for their intended purpose. Biopolymers are biocompatible polymeric materials that could be appropriate for treating certain neurosurgical complications. Biopolymers can respond to both the physiological and biological environments, and the kind of response is the main characteristic that determines whether the biopolymer should be used to construct biomedical devices or be applied in advanced neurosurgical applications. To our knowledge, there are three classifications of biopolymer medical-associated applications: (i) synthetic polymers, (ii) tissue engineering, and (iii) controlled-release agents. For cerebrovascular surgery applications, biopolymers have been applied to create new types of responsive delivery systems. This kind of polymer is needed to treat certain complications during cerebrovascular surgery, such as cerebrovascular spasms. When polymers are fabricated as controlled-release agents, they must have the appropriate mechanical characteristics that are suitable for use as drug delivery agents to treat vasospasms [3–5].

Due to the short biological half-life of NCH, we were able to modify the NCH pharmacokinetics via carboxymethyl cellulose/poly(d,l-lactide-co-glycolide) (NCH-CMC/PLGA) nanoparticles using a contemporary emulsion process [6]. PLGA is an aliphatic polyester with hydrophobic properties that is highly biocompatible and biodegradable. The insolubility of PLGA was improved by the addition of CMC to increase the hydrophilicity of these nanoparticles to enhance the therapeutic index. These nanoparticles gave rise to a new drug delivery system that was capable of solving some of the major bottlenecks of the NCH-PLGA microparticles prepared by the double emulsion process in our previous research [7]. The NCH-CMC/PLGA nanoparticles were flexibly designed to protect the developed delivery system against the drug degradation observed in the absence of a delivery system and improve the insufficient drug release during the first 6 days of microparticle treatment. These nanoparticles had a rate of drug release and a daily dose that was sufficient to treat vasoconstriction during the 4–14 days that this condition could occur. The results demonstrated that the designed aliphatic polyester nanoparticles had wide application prospects in drug delivery systems. These polymeric nanoparticles could release drugs on demand and are easily customized depending on the desired application. Potentially, these same nanoparticles could be extended to many fields and fulfill the different purposes of delivery systems; for example, in the food, pharmaceutical, cosmetics, biotechnology, and sustainable agriculture industries. Consequently, this chapter focuses mainly on describing the core characteristics of aliphatic polyester nanoparticles fabricated using an emulsion process.

## **2. Aliphatic polyesters**

Currently, biodegradable polymers are utilized as a component of drug delivery systems. There are a large number of literature reports that have studied aliphatic polyesters, and their high biocompatibility and biodegradability potential has been demonstrated. Most of these polyesters have been approved for use as drug delivery devices by the Food and Drug Administration (FDA) [8]. Among these studies, aliphatic polyesters have been used to circumvent several major challenges that occur during drug delivery applications. In the 1960s, these polymers were initially

used with drug delivery systems to control drug release [9]. They can improve pharmacokinetics by maintaining the concentration of the drug at a therapeutic level and minimizing side effects.

Aliphatic polyesters are linear polymers with repeating units formed through ester linkages (R1▬COO▬R2). They are classified into two types according to the structure of their repeating units, poly(alkylene dicarboxylate)s and poly(hydroxy acid)s, as summarized in **Figure 1**. Poly(alkylene dicarboxylate)s consists of two types of repeating units between succinic acid (HOOC▬(CH2)2▬COOH) and alkanediol (HO▬R▬OH) and are prepared by esterification [10, 11]. Examples include poly(eth ylene succinate) (PES), poly(butylene succinate) (PBS), and poly(butylene succinate-co-butylene adipate) (PBSA). Additionally, poly(hydroxy acid)s are aliphatic polyesters that have hydroxy acid (HO▬R▬COOH) repeating units that consist of carboxylic acid (▬COOH) and hydroxyl (▬OH) groups. These polymers can be further classified according to the bonding position of the hydroxyl group (α, β, or ω) in the polymer chain. As a result, these hydroxy acids containing hydroxyl groups can be classified as poly(α-hydroxy acid)s, poly (β-hydroxyalkanoate)s, and poly(ω-hydroxyalkanoate)s.

Poly(α-hydroxy acid)s have a hydroxyl group attached to the α-carbon (or first carbon) atom bonded to the carboxylic acid. Poly(lactide) (PLA) and poly(glycolide) (PGA) are members of the poly(α-hydroxy acid) family with repeating lactic acid and glycolic acid units, respectively. PLA has three stereoisomers: poly(l-lactide) (PLLA), poly(d-lactide) (PDLA), and poly(d,l-lactide) (PDLLA). Furthermore, poly(d,l-lactide-co-glycolide) (PLGA), another member of this family, is formed from a block copolymer containing both PDLLA and PGA [10, 12, 13]. Poly(β-hydroxyalkanoate) has a hydroxyl group bonded to the β-carbon of the carboxylic acid, which is the carbon atom next to the α-carbon.

**Figure 1.** *Classification and examples of aliphatic polyesters [10].*

This family includes poly(hydroxyalkanoate), i.e., poly(3-hydroxybutyrate) (P3HB), poly(3-hydroxyvalerate) (P3HV) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), etc. Additionally, hydroxyl groups attached to a carbon that is three or more carbon atoms away from the carbonyl are poly(ω-hydroxyalkanoate)s, such as poly(ε-caprolactones) (PCL) [10, 13]. The ester linkages of these polymers can be degraded under physiological conditions, and their degradation products are nontoxic to human connective tissue.
