In vitro analysis of the release of antimicrobials in hydroxyapatite, chitosan and carbon nanotube composites as a drug delivery device

Author(s)

Maria Raquel Bellomo Agrello Ruivo

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2020-10-22

Examining board members

André Luis do Valle de Zoppa; Geissiane de Moraes Marcondes; Ana Maria de Guzzi Plepis

• Advisor: André Luis do Valle de Zoppa

Abstract

The difficulty in controlling osteomyelitis motivates the search for alternative treatments, which are efficient for this type of condition. Drug delivery devices have been an alternative in these cases, as they increase the activity of the chosen drug, decrease the dosage interval and establish high levels of concentration in the desired location. In this work, chitosan, carbon nanotubes and hydroxyapatite (QNCHA) composites, amikacin sulfate, gentamicin sulfate and ciprofloxacin hydrochloride were incorporated. The incorporation of antibiotics was carried out by two methods: during the preparation of the matrices, in concentrations 5% and 10% in relation to the dry mass, and by immersion in concentrated antibiotic solution. The objective of this work was to study the in vitro antibiotic release, obtaining these values by UV-visible spectrophotometry. The composites were placed in a phosphate buffered saline solution (PBS), pH 7.4, and made available in Dubnoff Bath. The aliquots were collected at predetermined times and the study was carried out in quintuplicate. The composites, despite having low porosity, were able to reach relatively high release rates, being observed mainly in the groups impregnated with aminoglycosides. The PBS swelling test was able to show its good absorption capacity. This study demonstrated higher release values in groups containing aminoglycosides compared to those impregnated with ciprofloxacin. Amikacin composites showed a constant release pattern after six hours of analysis, reaching statistically equal maximum release values (P = 1). Regarding gentamicin, Group 5% and immersion have similar maximum release with statistically equal values (P = 0.82), and Group 10% in 24 hours of analysis reached the highest percentage of antibiotic released, reaching 90 , 3 ± 9.2%. The groups impregnated with ciprofloxacin compared to the aminoglycosides obtained the lowest percentage of release. For Groups 5 and 10%, statistically different values were obtained (P = 0.017). There was also a statistical difference when comparing Group 5% and immersion (P = 0.007) and Group 10% with immersion (P = 0.015). The release profiles were more suitable for the Weibull and Korsmeyer-Peppas models. Although Weibull\'s model is empirical and does not reflect release kinetics, he showed that release profiles tend to be parabolic. The release study for aminoglycosides showed that the prevailing process is diffusion, however, for gentamicin 10%, zero-order kinetics was observed, that is, a very fast and time- independent release. In the case of ciprofloxacin, a quasi-Fickian mechanism was observed. It was concluded that the composites showed good release capacity and when considering the Minimum Inhibitory Concentration (MIC), the amount of antibiotic released in all groups in a 24-hour period, had the potential to combat some orthopedic infections. (AU)

• FAPESP's process: 18/04924-6 - In vitro analysis of antimicrobial release in composites of hydroxyapatite, chitosan and carbon nanotube for bone regeneration
• Grantee: Maria Raquel Bellomo Agrello Ruivo
• Support Opportunities: Scholarships in Brazil - Master