## 4 Application of PCL-Based Materials in Nanoformulations
### Nanoparticles
Most cancer cells are found in an acidic environment, which stimulates the development of pH-sensitive drug delivery systems. This helps to reduce the harmful side effects of drugs used to treat cancer. Systems have been developed to respond to these stimuli and increase drug delivery to the target site [40]. [PERSON] et al. prepared pH-sensitive copolymer micelles. These micelles, which measure approximately 100 nm, were obtained from a diblock copolymer of PEG and PCL linked by a pH-sensitive hydrazine (Hyd) bond, using a solvent evaporation method. The micelles were loaded with Paclitaxel (PTX), an anticancer drug. The results showed that these pH-sensitive and biodegradable copolymer micelles containing hydrazine exhibited strong toxicity against HepG2 cells [118]. In a different study, poly(\(\epsilon\)-caprolactone) micelles grafted onto guar gum (GG-g-PCL) were prepared using a membrane dialysis method to load ketoprofen. Approximately 18% by weight of the drug was loaded into micelles ranging in size from 75 to 162 nm. Drug release was characterized by an initial rapid release, followed by sustained release over a period ranging from 10 to 68 hours [119]. [PERSON] et al. [120] created amphiphilic graft copolymer systems of polyethyleneenimine (PEI)-polycaprolactone (PCL) by combining non-viral gene therapy drugs with chemotherapy drugs to be used against aggressive cancers. They encapsulated the anticancer drug doxorubicin (Dox) and p53 plasmid DNA in positively charged nanoparticles (about 159 nm) with a hydrophobic core and a hydrophilic shell. The synergistic effect of Dox and p53 plasmid DNA showed better cytotoxic efficacy against human hepatoma and human cervical adenocarcinoma cell lines compared to their single-agent counterparts. In another study, linear, 3-arm, and 6-arm star-shaped PCL-poly(quaternary ammonium salt) copolymers were synthesized using a combination of ring-opening polymerization and atom transfer polymerization. The hydrophobic PCL block formed the core, while the hydrophilic poly(quaternary ammonium salt) blocks served as the shell of the micelle. The antibacterial drug triclosan was loaded into these solvent-evaporated micelles. The efficacy of all types of micelles against _Escherichia coli_ was reported, with star-shaped micelles showing better antibacterial properties [94]. Amphiphilic micelles of a multi-armed copolymer based on PCL/PEG and cyclodextrin developed by [PERSON] et al. [121], have shown great efficiency in encapsulating DOX due to the adequate space present in this system. The in vitro release of the drug was studied using electrochemical control. In vitro release studies of DOX from star-shaped copolymer micelles have shown that this anticancer drug can be released over several hours. The ability of multi-armed copolymers to load and encapsulate a large number of drugs compared to linear analogues has been demonstrated in several other studies that have addressed drug delivery applications (Table 1) [122]. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Mode** & **Polymers** & **Drug** & **Nanoformulation** & **Therapeutic Target** & **Biological Evaluation** & **Ref. ** \\ \hline Electrospun & PCL & Dexamethasone & Nanofibers & Biomedical applications, particularly in the eye. & Although the results are encouraging, further in vitro studies and finally in vivo animal studies are needed to determine the comfort and retention. & [123] \\ \hline Electrospun & PCL & Tetracycline/gcyclodextrinrin & Nanofibers & Controlled release systems and their clinical application. & Strong adhesion and reduced demineralization of dentin. & \\ \hline Electrospun & PCL & ampicillin & Nanofibers & High antimicrobial activity against A\(\cdot\) and P\({}_{\delta}\) \\ \hline Electrospun & PCL & Seeded with IYFP and chondrocytes & Nanofibers & Restore the functional cartilage in articular disorders. & A positive effect on the differentiation of IYFP PACs into chondroic cells. & [126] \\ \hline Electrospun & PCL & Tetracycline/gcyclodextrinrin & & Un