Novel bioactive hydrophobic gentamicin carriers for the treatment of intracellular bacterial infections.
Gentamicin (GEN) is an aminoglycoside antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, its poor cellular penetration limits its use in the treatment of infections caused by intracellular pathogens. One potential strategy to overcome this problem is the use of particulate carriers that can target the intracellular sites of infection. In this study GEN was ion-paired with the anionic AOT surfactant to obtain a hydrophobic complex (GEN-AOT) that was formulated as a particulated material either by the precipitation with a compressed antisolvent (PCA) method or by encapsulation into poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The micronization of GEN-AOT by PCA yielded a particulated material with a higher surface area than the non-precipitated complex, while PLGA NPs within a size range of 250-330 nm and a sustained release of the drug over 70 days were obtained by preparing the NPs using the emulsion solvent evaporation method. For the first time, GEN encapsulation efficiency values of ∼100% were achieved for the different NP formulations with no signs of interaction between the drug and the polymer. Finally, in vitro studies against the intracellular bacteria Brucella melitensis, used as a model of intracellular pathogen, demonstrated that the bactericidal activity of GEN was unmodified after ion-pairing, precipitation or encapsulation into NPs. These results encourage their use for treatment for infections caused by GEN-sensitive intracellular bacteria.
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
Edurne
E
Imbuluzqueta
Elisa
E
Elizondo
Carlos
C
Gamazo
Evelyn
E
Moreno-Calvo
Jaume
J
Veciana
Nora
N
Ventosa
María J
MJ
Blanco-Prieto
D000890:Anti-Infective Agents / Q000494:pharmacology; D017347:Brucella melitensis / Q000187:drug effects; D002006:Brucellosis / Q000188:drug therapy* / Q000382:microbiology*; D011232:Chemical Precipitation / Q000187:drug effects; D003460:Crystallization; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005839:Gentamicins / Q000494:pharmacology* / Q000627:therapeutic use*; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology*; D019344:Lactic Acid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000494:pharmacology; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014961:X-Ray Diffraction
D000890:Anti-Infective Agents; D004337:Drug Carriers; D005839:Gentamicins; D012997:Solvents; D004143:Dioctyl Sulfosuccinic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol