In vitro analysis of a local polymeric device as an alternative for systemic antibiotics in Dentistry

Abstract

The development of a biodegradable material with antimicrobial properties for local applications is required in the prevention and treatment of infectious diseases. The objective of this study was to produce blends of poly-L-lactide acid (PLLA) synthetic polymer associated with several antimicrobials, as an alternative in the prevention and treatment of infections, as well as to evaluate its cytotoxicity, release of antimicrobials and inhibit bacteria growth. Blends of PLLA added with 20% Amoxicillin, Metronidazole, Clindamycin or Azithromicyn were used to produce Films (F) or Meshs (M) by casting and electrospinning methods, respectively. Standardized discs of the films and meshs were stored in buffer solutions (pH 5 or 7.4) and aliquots were analyzed by high performance chromatography (HPLC) during 168 hours. Cytotoxicity on human gingival fibroblasts was tested after 24, 48 and 72h by MTT reaction. The antimicrobial capacity was determined against P. gingivalis and S. pyogenes. The specimens were weighed after 3 and 6 months of storage for degradation analysis. SEM was performed to control interfaces and degradation. Antimicrobials presented a continuous and exponential drug release. Analysis showed that both M and F were able to inhibit S. pyogenes and P. gingivalis growth, indicating the release of active antimicrobial agents. The products were not toxic to the fibroblasts. Amoxicillin-film showed more degradation than PLLA at both pHs (p < 0.05), whereas Azithromycin-meshes were more degraded than PLLA at pH 7.4 (p < 0.05). PLLA association with antimicrobials is biocompatible and may represent a potential tool for the local delivery of antimicrobials.

Engineering of Injectable Antibiotic-laden Fibrous Microparticles Gelatin Methacryloyl Hydrogel for Endodontic Infection Ablation

“…In light of verifying the degradation ability of the hydrogels, we performed two different tests: hygroscopic swelling and in vitro enzymatic degradation. As shown in Figure 2A, the antibiotic-modified hydrogels absorbed a greater amount of humidity (PBS) when compared with the neat GelMA, probably due to the hydrophilic nature of CLIN and MET [27]. Both of these antibiotics are comprised of hydroxyl groups, hence increasing polar interactions and the formation of hydrogen bonding.…”

“…Despite the fact that we did not conduct any analysis to determine the porosity level of the fiber mats, one should note that the MET-laden fibers showed the thickest morphology and the most porous fiber architecture. Thus, the total amount of GelMA matrix embedded within the fiber mat was also probably higher, turning the MET fibrous particles more prone to hydrolysis [27]. This may explain the more intense hygroscopic swelling and biodegradation patterns demonstrated by the MET and CLIN+MET hydrogels when compared with the CLIN group.…”

“…The CLIN-based fibers presented the thinnest average fiber diameter of 628 nm (±194 nm), which was lower than the PLGA fibers (729 ± 214 nm) and the MET-based fibers (1.3 ± 0.3 µm). Here, both antibiotics (CLIN and MET) possess a hydrophilic nature [27], which may decrease the viscosity of the polymer solution, allowing for the formation of thinner fibers [28]. However, the METbased fibers did not show such thin distribution, exhibiting ca.…”

“…Considering that electrospun fibers may result in the burst release of drugs during the first 24 h [16,27,29], we have further processed them into small-sized particles, aiming to obtain a more controlled and sustained release of CLIN/MET. The method used here was cryomilling, which consists of cooling the material, then reducing it to smaller particles.…”

“…The foregoing bacteria are usually pathogenic and difficult to eliminate, but as verified by our findings, the strategy of using a hydrogel system incorporated with antibiotics resulted in important inhibition values, although it was dependent on the type of antibiotic(s) used, as well as the type of bacteria tested. While CLIN is typically a bacteriostatic agent, acting on the inhibition of bacterial protein synthesis [27], MET is a bactericidal antimicrobial competing with the biological electron acceptors of bacteria, disturbing their energy metabolism, and thus causing cell death [27]. Having this in mind, MET was expected to be less effective against Gram-positive (G+) bacteria, which presents a more organized cell wall structure, compared with the Gram-negative (G-) counterparts.…”