## 4 Application of PCL-Based Materials in Nanoformulations
### Nanoparticles  
Colloidal systems based on PCL are of great interest due to their use as drug carriers [100]. Self-assembled structures (micelles) have been widely studied as encapsulation agents for various drugs and proteins [101]. The use of nanocarriers for drug delivery arose from the need to find new vehicles for bioactive agents that would provide pharmacokinetic profiles that mimic the normal pattern of these agents, when the therapeutic efficacy of many of these agents is limited by the therapeutic index and selectivity [102]. Encapsulation methods improve and prolong the stability of bioactive drugs, enhance therapeutic efficacy by adapting the precise amount of drug to achieve the desired therapeutic response, and prevent degradation and nonspecific uptake by cells, thus minimizing side effects [103]. The structure of a transport system has a major impact on the loading of bioactive drugs and affects their release, cellular internalization, and in vivo biodistribution [104]. Micellar structures and micro- or nanoparticles of different morphologies allow for better control of degradation rates, release behavior, or drug distribution in the body [78]. An analysis of the literature, as well as these examples, show that a large part of the evaluation of multi-armed PCL-based polymers in nanoparticle formulation design has focused on drug loading and release, as well as in vitro studies on different cell lines, generally related to cancerous tissues. Some in vivo studies have also been conducted, but they remain few in comparison. For example, in amphiphilic polymer-based multi-armedmicelles with dimensions of 10-100 nm, they are known to reduce protein-nanoparticle interactions and avoid nanocarrier elimination by phagocytosis [105]. To limit RES-based elimination and improve blood retention and circulation, copolymers can bind to drug molecules to increase their molecular weight, thereby reducing their elimination kinetics and increasing their effectiveness. The nanoparticles then follow passive pathways (enhanced retention by permeation) or active pathways (using targeting motifs) to reach the extracellular space. Accumulation at tumor sites depends on the cam-outflage, stability, blood circulation/retention, targeting ability of the nanoparticles, and other factors such as vascularization and angiogenesis [106]. Nanoformulations using multi-arm amphiphilic polymers help solve these RES-based elimination problems by modulating the density of the nanoparticle corona and facilitating the introduction of functional groups for active transport and drug release in response to stimuli. Cellular internalization of nanoparticles can occur through specific interactions with receptors, endocytosis, nonspecific association with the cell membrane, and absorption by pinocytosis [107]. Thanks to controlled and targeted drug efficiency, as well as their great ability to cross physiological barriers, biodegradable polymer nanoparticle-based delivery systems have shown sustained drug activity. Additionally, in addition to their reduced systemic side effects, drug-loaded nanoparticle systems reduce costs for patients and risks of toxicity. In this case, particle size is the primary parameter that influences targeting capabilities and penetration through physiological barriers. PCL-based nanoparticles have generally been prepared using several techniques such as solvent evaporation-emulsification, nano precipitation, and solvent displacement methods, which provide richness in the operating modes used. During nanoparticle preparation, several parameters must be optimized, such as drug-polymer concentrations, homogenization speed and time, and types of solvents used. The effect of these parameters on the properties of curcumin-loaded PCL nanoparticles has been studied in the work of [PERSON] et al. [108]. In this study, PCL nanoparticles loaded with curcumin (with a diameter of about 390 nm) were prepared using the solvent emulsification and evaporation technique.