Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa

Abstract

Amikacin is a very effective aminoglycoside antibiotic but according to its high toxicity, the use of this antibiotic has been limited. The aim of this study was to formulate and characterize amikacin loaded PLGA nanoparticles. Nanoparticles were synthetized using a solid-in-oil-in-water emulsion technique with different ratio of PLGA 50:50 (Resomer 502H) to drug (100:3.5, 80:3.5 and 60:3.5), two different concentrations of stabilizer (pluronic F68) (0.5% or 1%) and varied g forces to recover the final products. The most efficient formulation based on drug loading (26.0±1.3μg/mg nanoparticle) and encapsulation efficiency (76.8±3.8%) was the one obtained with 100:3.5 PLGA:drug and 0.5% luronic F68, recovered by 20,000×g for 20min. Drug release kinetic study indicated that about 50% of the encapsulated drug was released during the first hour of incubation in phospahte buffer, pH7.4, 37°C, 120rpm. Using different cell viability/cytotoxicity assays, the optimized formulation showed no toxicity against RAW macrophages after 2 and 24h of exposure. Furthermore, released drug was active and maintained its bactericidal activity against Pseudomonas aeruginosa in vitro. These results support the effective utilization of the PLGA nanoparticle formulation for amikacin in further in vivo studies.

Physico-Chemically Distinct Nanomaterials Synthesized from Derivates of a Poly(Anhydride) Diversify the Spectrum of Loadable Antibiotics

“…For instance, despite the two aminoglycosides tested, amikacin and neomycin, presenting similar MWs (585.6 and 614.6 g/mol, respectively) and chemical structures (see Figure 1), the size change of their encapsulating nanostructures (625 vs. 304 nm in nanofibers and 253 vs. 209 nm in nanoparticles) and their EEs (14% vs. 40%) are very different. In this regard, the scarcity of nanoencapsulation studies for amikacin, neomycin cefotaxime and, to a lesser extent, ciprofloxacin [40][41][42][43], hampers any meaningful assessment or comparison.…”

Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

“…Gentamicin mechanism of action involves irreversible binding to 30S ribosomal subunit, inhibition of messenger RNA (mRNA) complex formation leading to protein synthesis prevention and resulting in cell bacteria death. Additionally, as all aminoglycoside antibiotics, gentamicin can cause membrane damage altering ionic concentration [ 1 ]. The conventional multiple dosing regimens result in adverse reactions due to fast gentamicin clearance, or its unfavorable biodistribution, causing nephrotoxicity and ototoxicity.…”

Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy

“…Drugs’ release profile can be altered by modifying polymer properties or adjusting scaffold physical and chemical properties such as porosity, pore size, and shape (e.g., tortuosity), polymer crosslinking degree, and degradation rate. Additionally, drugs and cells can be encapsulated into biodegradable particulate systems having the potential to be retained in specific tissues, providing sustained release [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 78 ]. Figure 2 shows a scheme of drug release mechanism from polymeric biodegradable microspheres that combines drug diffusion through a polymer matrix and polymer degradation.…”

“…The nanoparticles demonstrated significant improvement of antimicrobial effect, above all in the murine model, as indicated by a reduction of inflammatory indicators interleukin-6 and myeloperoxidase [ 81 ]. Literature on polymer and metal nanoparticles shows that many questions are still open about the antibacterial mechanism of nanoparticles, also depending on the material used to make them [ 78 , 79 , 83 , 120 , 121 ]. Moreover, an issue related to nanoparticles loaded with antibiotics is the usually low drug content if compared with the high antibiotic dose regimens required [ 78 , 79 , 80 , 81 , 82 , 83 ].…”