## 3 Results
### Drug Load and Release  
The study of the drug loading process was done considering two points: the amount of drug loaded in the specimen and its homogeneity (i.e., the drug can be distributed in a non-homogeneous way along the flow direction). Note also that some amount of drug should rest in the sprue and consequently the drug effectively incorporated in the specimen is different to the amount of drug loaded in the processing chamber. Therefore, results will be always referred to as the percentage of drug in each evaluated specimen. In order to determine the uniformity of the drug distribution, the specimen was cut in three parts along the flow direction as shown in Figure 11a. The percentage of drug incorporated in each section was determined by UV measurements of three replicas. Comparison between the average values determined for each one of the three parts allowed for getting an idea about the homogeneity of the sample.  
Figure 11: Schematic representation of the three selected sections for each specimen (**a**). Percentage of loaded CHX (**b**) and TCS (**c**) drugs for the three specimen sections with respect to the percentage introduced in the processing chamber.  
Figure 10: Thermogravimetric and differential thermogravimetric profiles of ultrasound processed specimens of PLA and PLA loaded with 6 wt-% of each drug. Magnification of onset temperature region and DTGA peaks are shown in the insets.  
Figure 11b,c compare the theoretical percentage that should be loaded and the real percentage incorporated in each analyzed section. The loading efficiency was around 83-86% for both drugs, independently of the total load. A relatively good distribution along the flow direction was found, although the proximal region (i.e., that closest to the sprue) tended to have a slightly higher percentage. Results attained with CHX and TCS were similar despite the great differences in molecular size and even in their hydrophobic character.  
Release studies were performed in static conditions, which are obviously different to the continuous renewal of the medium that occurs in the human body. The performed study tries to use media with different polarity (i.e., by controlling the PBS:ethanol ratio) in order to evaluate drug retention and compare kinetic data. Specifically, the release assays were carried out in two types of media: ethanol and a PBS-ethanol mixture with 70% of PBS. Ethanol was selected in order to favor the drug release due to its capability to swell the PLA matrix. The second medium kept a certain content of ethanol and had a similar hydrophobicity of a typical serum medium as has previously been reported [32; 33].  
The release profiles of both drugs in the PBS-ethanol medium are shown in Figure 12 (dashed lines). These releases follow a first order kinetic without a significant burst effect. The release rate was slow and specifically 155 h were required for a delivery of 50%. This release was faster for the more hydrophilic CHX drug (i.e., \(k_{1}\) values of 0.0356 h\({}^{-1}\) and 0.027 h\({}^{-1}\) for CHX and TCS, respectively). The specimens were clearly too wide and compact to get a complete release in the limited exposure time of 155 h.  
Ethanol media increased the release rate and allowed the release of drugs located in the inner part. Specifically, release percentages of 85% and 75% were achieved after 165 h. This release was characterized by a clear burst effect (40-45% after only 8 h of exposure) of drugs located near the outer layer of microspecimens followed by a first order kinetic process with values of the same magnitude order of those found in the PBS containing medium (i.e., 0.0367 h\({}^{-1}\) and 0.0297 h\({}^{-1}\) for CHX and TCS, respectively).