*3.2.1 Single emulsion method*

Oil-in-water emulsification (O/W emulsion) can be used to prepare nanospheres that are ideal for entrapping hydrophobic drugs (i.e., steroids) [19] or water-soluble drugs entrapped on nanosphere surfaces [27]. Examples include amoxicillin-loaded PCL micro/nanospheres modified surface by chitosan for antibacterial applications. The amino groups (▬NH3 + ) of chitosan interact with PCL via carboxylate anions (▬COO<sup>−</sup> ) on the micro/nanosphere surface. Amoxicillin is encapsulated by the electrostatic interactions between the negative charges of the drug and the residual positive charge on the surface of chitosan, as observed by the zeta potential values of −20.03 mV and +53.93 mV, respectively. This study varied the ratios of PCL:chitosan to be 1:1, 1:3, and 1:5, and the results showed that increasing the ratio improved the encapsulation efficiency (~73–83%) and controlled drug release (~5.76–6.56 mg) over 7 days compared to amoxicillinloaded PCL micro/nanospheres, which showed rapid drug release within 12 h due to the low encapsulation efficiency (~5.4%). Additionally, the amoxicillin-loaded PCL micro/nanosphere modification inhibited microbial growth, but the chitosanfree micro/nanospheres were less effective [27].

#### *3.2.2 Double emulsion method*

Water-in-oil-in-water (W1/O/W2) double emulsions could be used to prepare nanocapsules for the loading of water-soluble molecules, such as hydrophilic drugs, proteins, peptides, and vaccines [19]. This system is an extraordinarily complex

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

dispersion system of liquid membranes. In addition, the contemporary W1/O/W2 double emulsion method led to the preparation of PLGA nanocapsules. This emulsion method can enhance the solubility of poorly soluble drugs in the medium. As mentioned previously in the introduction, we prepared NCH-CMC/PLGA nanocapsules via a contemporary emulsion process. The composition of phase W1 included NCH and CMC. Notably, NCH dissolves in citric acid solution, but CMC is insoluble in acidic solutions, as citric acid is a crosslinking agent of CMC. This method fabricated two systems, citric acid crosslinking droplets and CMC droplets. To generate the crosslinking droplets, solid NCH was first dissolved in citric acid mixed poly(vinyl alcohol) (PVA) solution (W1). This solution was then added to an organic solution of PLGA with stirring (O). Similarly, the CMC solution (W1) was added to PLGA solution with stirring, forming CMC droplets. Both droplets were added together and ultrasonicated to form crosslinked droplets (W1/O single emulsion). This single emulsion was again added and ultrasonicated, forming the W1/O/W2 double emulsion. This unique synthesis enhanced the drug loading of the nanoparticles for controlled drug release for up to 16 days. As a result, NCH-CMC/PLGA nanoparticles containing calcium channel blockers were created. This method paved the way to generate a treatment for the prevention of vasospasm complications after surgery for ruptured intracranial aneurysms. There are several applications for calcium channel blocker prolonged-release implants. This application involves the binding of calcium channel blockers in composite polymer formulations for slow release at a rate that is effective to treat cerebral vasospasm in animal models. This drug delivery system is objectively locally positioned at the surgical site after the intracranial aneurysm is secured. These nanoparticles are located around the inflamed vessels and can avoid being washed away. The strategy for controlled release is based on polymer degradation at a rate that is effective for the treatment of cerebral vasospasms for 4–14 days. However, a clinical scenario needs to be investigated in the future [6].
