This work focuses on the development of a lipid-based nanocarrier for the delivery of quinolones, as a therapeutic strategy against pulmonary infection in cystic fibrosis patients. Cystic fibrosis patients often suffer of pulmonary infections, caused by opportunistic bacteria which are able to colonize the lungs protected by the hypersecretion of high viscosity mucus. Antibiotherapy is hindered by the of pulmonary mucus and also by resistance mechanisms of some bacteria. The use of nanoparticles as vehicle of administration, can improve the local concentration leading the antibiotic direct to the site of action, allowing in addition, the controlled release of the drug from the nanoparticles which increases the time of permanence in the lungs preventing resistance and enhancing the antibiotic activity. Fluoroquinolones loaded nanostructured lipid carriers were developed taking into account lipid composition and concentration. Preliminary solubility studies were conducted separately, testing Levofloxacin and Ciprofloxacin in four different liquid lipid Capryol 90, Capryol PGMC, Mygliol and Oleic acid and in three solid lipid Gelucire 44/14, Softisan 601 and Precirol. Softisan 601 and Gelucire, both with proven similar capacity to disperse the drugs,were selected on the basis of solubility studies as solid lipids and Capryol 90 as liquid lipid. Various concentrations have been tested to prepare the lipophilic phase that will be combined with a 5% (w/w) solution of Tween 80, using the hot high pressure homogenization technique. In accordance with the best chemical-physical properties obtained, Softisan 601 and Capryol 90, with a solid:liquid lipid ratio of 25 % of solid lipid and 75% of liquid lipid, were chosen for the loading of Levofloxacin and independently of Ciprofloxacin, testing increasing drug content since 5% to 15%. Afterwards, the impact of the time in a range of 2.5 to 10 minutes in high pressure homogenization on the colloidal properties of the nanocarriers was investigated. Chitosan, biopolymer commonly used to coat nanoparticles, was introduced in the nanosystem with different concentrations 0.5 and 1%(w/w). In conclusion, a sustained drug release performance of the NLCs developed was confirmed by in vitro release studies conducted for 24 h using static vertical Franz diffusion cell.
Sviluppo di nanoparticelle lipidiche per la veicolazione di chinoloni Questo lavoro di tesi è focalizzato sulla produzione di nanocarrier lipidici per la veicolazione di chinoloni, come promettente strategia contro infezioni polmonari in pazienti affetti da fibrosi cistica. I pazienti di questa patologia spesso soffrono di infezioni polmonari causate da batteri opportunisti capaci di colonizzare i polmoni e che sono protetti dall’ ipersecrezione di muco molto viscoso. La terapia antibiotica è ostacolata dalla presenza del muco polmonare e da meccanismi di resistenza di alcune specie batteriche. L’ utilizzo di nanoparticelle come veicolo per la somministrazione può migliorare la concentrazione locale e portare l’antibiotico al sito d’azione, permettendo inoltre il controllo del rilascio del farmaco e aumentandone il tempo di permanenza nei polmoni, prevenendo resistenza e migliorando l’attività antibiotica. Sono stati sviluppati nanocarrier lipidici caricati con fuorochinoloni tenendo conto della composizione e della concentrazione lipidica. Studi preliminari di solubilità sono stati condotti separatamente, testando la solubilità di levofloxacina e ciprofloxacina in quattro diversi lipidi liquidi Capryol 90, Capryol PGMC, Mygliol e Acido oleico e in tre lipidi solidi Gelucire 44/14, Softisan 601 e Precirol. Softisan 601 e Precirol, entrambi con comprovata capacità a disperdere i farmaci, sono stati scelti sulla base degli studi solubilità come lipidi solidi e Capryol 90 come lipide liquido. Sono state testate varie concentrazioni per preparare la fase lipofila che verrà combinata con una soluzione al 5% (w/w) di Tween 80, utilizzando la tecnica di omogenizzazione ad alta pressione a caldo. I test preliminari hanno permesso di scegliere Softisan 601 e Capryol 90, con un rapporto ponderale tra lipide solido: liquido pari a 25:75. Tale matrice lipidica ha permesso di ottenere un caricamento di farmaco fino 15%(w/w). Successivamente è stato esaminato l’impatto del tempo di omogenizzazione ad alta pressione sulle proprietà colloidali dei nanovettori considerando un intervallo di tempo tra 2,5 e 10 minuti. Il chitosano, un biopolimero comunemente usato per rivestire nanoparticelle, è stato introdotto nel nanosistema a diverse concentrazioni 0,5 e 1 % (w/w). In conclusione, il controllo del rilascio dei nanocarriers è stato confermato da studi di rilascio in vitro condotti per 24 ore con celle di Franz a diffusione statica verticale.
development of lipid-based nanoparticles for quinolones delivery
CANGEMI, MARCO
2018/2019
Abstract
This work focuses on the development of a lipid-based nanocarrier for the delivery of quinolones, as a therapeutic strategy against pulmonary infection in cystic fibrosis patients. Cystic fibrosis patients often suffer of pulmonary infections, caused by opportunistic bacteria which are able to colonize the lungs protected by the hypersecretion of high viscosity mucus. Antibiotherapy is hindered by the of pulmonary mucus and also by resistance mechanisms of some bacteria. The use of nanoparticles as vehicle of administration, can improve the local concentration leading the antibiotic direct to the site of action, allowing in addition, the controlled release of the drug from the nanoparticles which increases the time of permanence in the lungs preventing resistance and enhancing the antibiotic activity. Fluoroquinolones loaded nanostructured lipid carriers were developed taking into account lipid composition and concentration. Preliminary solubility studies were conducted separately, testing Levofloxacin and Ciprofloxacin in four different liquid lipid Capryol 90, Capryol PGMC, Mygliol and Oleic acid and in three solid lipid Gelucire 44/14, Softisan 601 and Precirol. Softisan 601 and Gelucire, both with proven similar capacity to disperse the drugs,were selected on the basis of solubility studies as solid lipids and Capryol 90 as liquid lipid. Various concentrations have been tested to prepare the lipophilic phase that will be combined with a 5% (w/w) solution of Tween 80, using the hot high pressure homogenization technique. In accordance with the best chemical-physical properties obtained, Softisan 601 and Capryol 90, with a solid:liquid lipid ratio of 25 % of solid lipid and 75% of liquid lipid, were chosen for the loading of Levofloxacin and independently of Ciprofloxacin, testing increasing drug content since 5% to 15%. Afterwards, the impact of the time in a range of 2.5 to 10 minutes in high pressure homogenization on the colloidal properties of the nanocarriers was investigated. Chitosan, biopolymer commonly used to coat nanoparticles, was introduced in the nanosystem with different concentrations 0.5 and 1%(w/w). In conclusion, a sustained drug release performance of the NLCs developed was confirmed by in vitro release studies conducted for 24 h using static vertical Franz diffusion cell.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/17721