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Nanoparticles as carrier for improve therapeutic efficacy of pioglitazone in ocular inflammatory disorders: development and validation of a high throughput LC-MS/MS method for quantitation in ocular tissues

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Abstract: Pioglitazone is an oral anti-hyperglycemic agent and it is used for the treatment of diabetes mellitus type 2. The anti-inflammatory activity has also been demonstrated in the literature. Pioglitazone belongs to Class II of Biopharmaceutical Classification System, i.e., slightly soluble and highly permeable. Polymeric nanoparticle formulations play an important role in the improvement of the efficacy of ocular therapies. These systems are non-toxic and biodegradable, show appropriate physicochemical characteristics as well as prolonged release profile suitable for ocular delivery. An accurate, sensitive, selective, reproducible and high throughput HPLC-MS/MS method was validated to quantitate pioglitazone in ocular tissues (cornea, sclera, lens, aqueous humour and vitreous humour). The chromatographic separation was achieved in 10 min on a Kinetex C18 column. Linear response of pioglitazone was observed over the range of 5-100 ng/ml. The limit of quantitation was 10 ng/ml (in extract). The recovery of pioglitazone or pioglitazone encapsulated in nanoparticles of polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) was in the range 85-115 % in all tissues and levels tested. The intra-day and inter-day precision were <5 % and <10 % respectively. The obtained extracts demonstrated to be stable under various experimental conditions in all the studied matrices. This method can be applied to in vivo and ex vivo biodistribution studies related to the ocular administration of pioglitazone nanoparticles.

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Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)

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Nanoparticles as carrier for improve therapeutic efficacy of pioglitazone in ocular inflammatory disorders: development and validation of a high throughput LC-MS/MS method for quantitation in ocular tissues