The main objective of this study was to synthesize hydroxyapatite-ciprofloxacin composites using a chemical precipitation method and to evaluate the properties and in vitro release profile of the drug from the hydroxyapatite-ciprofloxacin composites. Composite characterization was achieved by FT-IR, XRD and DLS. Ciprofloxacin determination was accomplished by HPLC, resulting in good incorporation efficiency of the drug (18.13 %). The in vitro release study (Higuchi model C = K t1/2 and Ritger-Peppas model, C = K t0.6) showed a diffusion-controlled mechanism. The antibacterial activity showed that the bacterial growth inhibition zones were approximately equal for the synthesis composites and for the mechanical mixture on the Staphylococcus aureus germ. The use of hydroxyapatite, which is a biocompatible, bioactive and osteoconductive material, with ciprofloxacin, which has good antibacterial activity in this composite, makes it suitable for the development of bone grafts. Furthermore, the synthesis process allows a slow local release of the drug.
The purpose of this study was to synthesize a PLGA (polylactic-co-glycolic acid)-gentamicin biodegradable material followed by HPLC determination of the drug's encapsulation efficiency in the polymer. The chosen polymer, PLGA is a biocompatible and biodegradable synthetic polymer, approved by the FDA, with adjustable mechanical properties, highly used as a controlled release drug delivery system. One novel feature of the study is the inclusion of an antibiotic in the composite material to combat the planktonic growth and biofilms formed by some of the major bacterial species involved in the aetiology of osteomyelitis. The double emulsion synthesis method was chosen, as the most suitable for encapsulating water-soluble drugs, such as gentamicin. For the quantitative assay of gentamicin, a new HPLC chromatographic method was used, consisting in an initial treatment with FMOC-Cl (9-fluorenylmethylchloroformate) to derivatize gentamicin, followed by UV detection of the derivative at λ = 265 nm. The antibacterial activity of the composite material was confirmed by the qualitative and quantitative assays performed in this study to determine the minimal inhibitory concentration and the minimal biofilm eradicating concentration. RezumatScopul acestui studiu l-a reprezentat sinteza unui material biodegradabil de tip PLGA-gentamicină, urmată de determinarea eficienţei de încapsulare a medicamentului în polimer. Polimerul ales, PLGA (acidul poli lactic-co-glicolic) este un polimer sintetic biocompatibil şi biodegradabil, aprobat de FDA, cu proprietăţi mecanice ajustabile, extrem de utilizat ca sistem de cedare controlată a medicamentelor. Un element de noutate al studiului îl reprezintă includerea în materialul compozit a unui antibiotic activ față de creșterea planctonică și față de biofilmele formate de principalele specii bacteriene implicate în etiologia osteomielitei. Ca metodă de sinteză s-a ales metoda emulsiei duble, aceasta fiind cea mai adecvată pentru încapsularea medicamentelor hidrosolubile, precum gentamicina. Pentru determinarea cantitativă a gentamicinei s-a utilizat o metodă cromatografică HPLC nouă, care a presupus iniţial derivatizarea gentamicinei cu clorură de 9-fluorenilmetilcloroformat (FMOC-Cl), urmată de detecţia UV a derivatului la λ = 265 nm. Activitatea antibacteriană a compozitului a fost confirmată prin metodele cantitative utilizate pentru determinarea concentrațiilor minime inhibitorii și de eradicare a biofilmului.
The aim of our study was to synthesize a biocomposite material using a natural polymer (collagen), hydroxyapatite and ciprofloxacin. We used Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), high performance liquid chromatography (HPLC-DAD) and scanning electron microscopy (SEM) for the physico-chemical characterization and we determined its antibacterial activity against Staphylococcus aureus Rosenbach (S. aureus), Pseudomonas aeruginosa (Schroter) Migula (P. aeruginosa), Klebsiella pneumonia (Schroter) Trevisan (K. pneumoniae) and Escherichia coli (Migula) Castellani and Chalmers (E. coli). The release profile of the ciprofloxacin chemisorbed in the material was also studied, and we found that the release was sustained for 30 days. RezumatScopul acestui studiu a fost acela de a sintetiza un material biocompozit cu ajutorul unui polimer natural (colagen), hidroxiapatitei şi ciprofloxacinei. Pentru caracterizarea fizico-chimică s-au folosit spectroscopia în infraroșu cu transformată Fourier (FT-IR), DLS, HPLC-DAD şi microscopia electronică de baleiaj (SEM), în timp ce activitatea antibacteriană a materialului obținut a fost determinată pe Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia şi Escherichia coli. Profilul de eliberare al ciprofloxacinei chemisorbite a fost de asemenea studiat, constatându-se o eliberare susţinută a antibioticului din material, pe o perioadă de 30 de zile.
Osteomyelitis continues to be a major concern when orthopedic surgery is performed. Orthopedic infections have an incidence of 5% to 10% but their management proves to be quite difficult due to both biofilm formation and limited access of the drug to the infected area when systemic treatment is employed. The aim of the study was to optimize the synthesis process of a gentamicin loaded poly(-lactic-co-glycolic) acid (PLGA) based biodegradable composite by varying parameters that affect both efficiency encapsulation and nanoparticle size. Furthermore, a kinetic study was conducted to study the biodegradation process of the polymer. Gentamicin loaded PLGA nanoparticles were obtained using the double emulsion technique which allows the variation of several factors such as gentamycin concentration, PLGA concentration, buffer concentration and stirring speed. Out of the four factors evaluated, gentamicin concentration had the highest impact on both encapsulation efficiency and nanoparticle size. A few relevant interactions between factors were also registered.
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