## 5 Coating Materials with Embedded Antibiotics and Other Antibofilm Agents
### Antibiotic Based Antib Biofilm Coatings
After the deposition of the polyelectrolyte multilayers was completed, the calcium carbonate core was dissolved by 0.2 M EDTA solution [35]. During this process, the negatively charged PSS molecules are entrapped inside the microcapsules imparting them with the capability to spontaneously load positively charged antimicrobial compounds like CH [33; 35]. The pH-tunable permeability of the walls of the microcapsules was evidenced by monitoring the incorporation of the fluorescent-labeled positively charged tetramethylrhodamine isothiocyanate (TRITC)-dextran polymer at different pH values. In alkaline media, e.g., pH = 8.0, the interior of the capsules remained dark, indicating that no loading of TRITC-dextran occurred. One says that the microcapsule is in its \"closed\" state. Under acidic conditions (pH = 3.0), strong fluorescence was observed, proving that a large amount of TRITC-dextran has penetrated the capsules walls getting inside the capsules [35]. Hence, the microcapsule state was switched from the \"closed\" state in alkaline conditions to the \"open\" state in acidic media. This was rationalized as follows: By decreasing the pH, more and more carboxylate groups of the PMA are protonated; hence, the positively charged ammonium groups in PAH remain uncompensated thereby developing an electrostatic repulsive force resulting in phase segregation and promoting the transition from a continuous to nanoporous morphology of the capsule walls [32; 34]. The excellent loading capacity for CH of PAH/PMA multilayer microcapsules (236 mg/mL) in acidic media (pH = 3.0) was attributed to two main reasons: (i) The higher degree of protonation of the permeant at pH = 3.0, and (ii) the increased permeability of the walls of the microcapsules in acidic media favoring the diffusion of the positively charged antibiotic molecules from the bulk into the interior of the capsules preloaded with the negatively charged polyelectrolyte PSS. The release of CH from PAH/PMA microcapsules was investigated in PBS (pH = 7.4). The release process was governed by a concentration-dependent diffusion mechanism. The release profile is characterized by an initial burst effect during the first 1 h, followed by sustained release. About 70% of the loaded antibiotic was released within 6 h; beyond this period of time, the release curve reached a plateau. The drug release rate could be further slowed down by crosslinking the wall components of the polyelectrolyte capsules. Crosslinking was achieved by incubating CH loaded microcapsules with 0.2 mM EDC at pH = 6.0, at room temperature [35]. The antibacterial efficiency was estimated by adding the bacterial pathogen _E. coli_ at an infective dose \(1.2\times 10^{7}\) CFU/mL to a suspension of CH loaded crosslinked PAH/PMA polyelectrolyte multilayer microcapsules and monitoring bacterial growth over time. Due to the sustained release of CH from the capsules, no bacterial proliferation was observed up to 10 h [35]. [PERSON] and coworkers [36] introduced a novel and robust gentamicin loaded hydroxyapatite (HAP) coating on titanium alloy (Ti-6 Al-4V) covered with a protective, biodegradable PLGA overlayer. HAPwas spray-coated on grit-blasted Ti-6 Al-4V, according to [PERSON]'s standard specification for the clinically established Corail(r) total hip system. Next, gentamicin sulfate was sprayed on HAP-coated, grit-blasted Ti-6 Al-4V coupons until the final concentration of 1 mg active ingredient/cm\({}^{2}\) was reached. Eventually, a PLGA layer was deposited over the HAP-containing gentamicin coating using an ultrasonic coating process. The biodegradable protective PLGA overlay prevents the rapid washout of the gentamicin layer by body fluids rather than controlling the antibiotic release. PLGA-gentamicin-HAP coatings showed an initial burst release of about 95% of the incorporated antibiotic during the first 1-2 h, which is very important since it immediately provides a very high local antibiotic concentration that kills bacteria introduced during the surgery and prevents biofilm development.