Preparation of gentamicin dioctyl sulfosuccinate loaded poly(trimethylene carbonate) matrices intended for the treatment of orthopaedic infections

Abstract

Lipophilic GEN-AOT was at least as potent as GEN-SULPH. For S. epidermidis it was even more potent than GEN-SULPH. More than 50% fibroblast cell viability was maintained at bactericidal concentration for both bacterial strains.

Insight in Superiority of the Hydrophobized Gentamycin in Terms of Antibiotics Delivery to Bone Tissue

“…AOT—unlike GentS—does not have any amine groups in its structure, which can be assigned to, e.g., the absorption band with maximum at 1620 cm −1 . This and a few other bands marked by a yellow color in Figure 1 in both GentS and GentAOT spectra, and not present in AOT spectra, consists of a sufficient proof of antibiotic modification according to Boo et al [ 33 ] who got similar results.…”

“…The bactericidal properties of GentAOT in relation to S. aureus (NCTC 12973) were already confirmed by Boo et al [ 33 ] who concluded that the efficiency of GentAOT in inhibiting the growth of this strain of bacteria does not change during the manufacturing process. In our study, the efficiency against MRSA (ATCC BAA 1681) was slightly higher, as the inhibition zone of 10 µg of GentAOT was 21 mm, whilst for the substrate GentS it was 20 mm ( Figure 2 E).…”

“…Based on DL and release studies it could be estimated that the concentration of gentamycin in the wells with 1000 µg/mL GS30-NPs after 72 h could be around 25 µg/mL whilst in the wells with 1000 µg/mL GA30-NPs around 112 µg/mL, making a significant difference. On the one hand, Boo et al [ 33 ] suggested that the increased bactericidal properties of GentAOT could have increased the potential to cross the cell membrane and showed that it is more toxic to hTERT fibroblast cells. On the other hand, there are different studies focusing on the cytotoxicity of pure gentamycin toward various cell lines.…”

“…In 2011, Imbuluzqueta et al [ 31 ] used the same approach for GentS ion pairing and encapsulated the product (GentAOT) within PLGA NPs, obtaining almost 100% of EE and continuous drug release also for the following 70 days and also confirmed its efficacy in vivo 2 years later [ 32 ]. In 2015, Boo et al [ 33 ] produced GentAOT with that technique, confirmed its bactericidal properties against Staphylococcus aureus and Staphylococcus epidermidis , and encapsulated it in poly(trimethylene carbonate) matrices for orthopedic infections. Recently, in 2020 Rotman et al [ 34 , 35 ] published two papers in which they encapsulated GentAOT in MPs from different biopolymers (poly(D,L-lactic acid) (PDLLA), PCL [ 34 ], and PCL modified with poly(aspartic acid) [ 35 ]) dedicated for the treatment of bone infections.…”

Formulation of Antimicrobial Tobramycin Loaded PLGA Nanoparticles via Complexation with AOT

“…With a view to increase the loading of tobramycin within the PLGA nanoparticles, we investigated the co-formulation of the drug with a surfactant (AOT) that has previously been used to increase the loading of other hydrophilic drugs within PLGA nanoparticles. This was achieved by increased lipophilicity of the drug-AOT complexes generated through ionic interactions; in this case the anionic sulfonate of the AOT and the cationic amine of tobramycin) [54,55,56]. To assess the lipophilicity of the tobramycin-AOT complexes, the extraction of tobramycin into organic solvents was assessed by a variety of methods.…”