## 4 Discussion  
This study suggests that the combination of PLGA, CS, and PEG can be used to form microspheres for the controlled release of cancer drugs such as paclitaxel and prodigiosin into cancer cells and tissues. The purpose of this study is to explore the effects of immobilized drug-loaded microparticles that are injected into regions from which tumor tissues have been extracted. Unlike the injectable drug-loaded nanoparticles that have sizes below certain critical sizes, the use of immobilized/implantable microparticle systems or scaffolds within a tumor site (after surgical removal of tumor to treat local regional/residual cancer tumor) has been reported to be safe [11; 12]. The extended release of paclitaxel and prodigiosin also inhibits the growth (reduces the viability) of MDA-MB-231 cells under in vitro conditions (Figure 6a,b). However, although further in vivo work is needed to investigate the possible outcome of extended cancer drug (prodigiosin and paclitaxel) release from the microparticles that were produced in this study, the current work does show that the combined use of PEG and CS polymer can be used to control the thermodynamics and the kinetics of the controlled release characteristics (Figure 4a-d and Tables 4 and 5). Furthermore, since the extended release of prodigiosin and paclitaxel from other PLGA microparticles did not elicit any observable cytotoxic responses in our prior work [12], we are hopeful that the in vivo elution of the same drugs (prodigiosin and paclitaxel) from PLGA-CS-PEG PEG microparticles will not induce cytotoxic effects. This suggests that the combination of two hydrophilic polymers (PEG and CS) could be advantageous in terms of preventing the adhesion of blood proteins to the surface, thereby improving the longevity in blood circulation. In any case, the in vitro drug release profiles obtained in this study (Figure 4a-d) exhibited a biphasic-controlled drug release from PLGA-CS-PEG microspheres with >50% drug released at day 30. This is because the result is characterized by an initial burst release of drug followed by a constant rate of drug release [54]. Thus, the burst release phase occurs because of the initial exposure of the microspheres to the phosphate-buffered saline and the next phase basically relates the power-law relationship between cumulative amount of drug release and time [55]. A similar biphasic release was observed in the work of [PERSON] and [PERSON] [34]. This controlled release can be attributed to the presence of CS and PEG as a blend, implying that they act as physical barriers that limit diffusion and erosion processes associated with drug transport through the microspheres. Hence, it was not surprising that the best fit to the drug release data obtained in this study was the Korsmeyer-Peppas model [11; 12; 47; 51]. This model corresponds to \(n\) values within the range \(0.45<n<0.89\), which is consistent with anomalous drug release by a combination of non-Fickian diffusion and erosion by polymer network degradation. The initial stage of drug release is due to diffusion from the polymer microspheres. However, the remaining drugs trapped in the microspheres are only released as the polymer degrades. Therefore, it is necessary to use a degradable material to slow the release of the drugsfrom the PLGA-CS-PEG microspheres. The use of PLGA polymer enables controlled release of drug due to their biocompatibility and degradability properties. Typically, as the drug-loaded microspheres break down inside the body, they produce nontoxic natural byproducts such as water and carbon dioxide that are easily eliminated [15; 16]. The occurrence of erosion by polymer network degradation is attributed to a two-step process in which the blend of hydrophilic polymers on the microspheres first form a swollen structure (due to water absorption) leading to the detangling of chemical, prior to the subsequent erosion of the PLGA microparticles.