In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration

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• 作者：Cristina Ca&ntilde ; adas^a ; Helen Alvarado^a ; ^b ; Ana C. Calpena^a ; Amé ; lia M. Silva^c ; ^d ; Eliana B. Souto^e ; ^f ; ^{ebsouto@ff.uc.pt" class="auth_mail" title="E-mail the corresponding author} ; Maria L. Garcí ; a^b ; Guadalupe Abrego^g
• 关键词：PF ; pranoprofen ; NPs ; nanoparticles ; pranoprofen-loaded nanoparticles ; PF-F1NPs and PF-F2NPs ; Z-Ave ; average particle size ; PI ; polydispersity index ; ZP ; zeta potential ; EE ; encapsulation efficiency ; cPF ; PF concentration ; cPVA ; PVA concentration ; PLGA ; Poly-l-lactic-co glycolic acid ; cPLGA ; PLGA concentration ; SA ; arachidonic acid sodium ; PBS ; phosphate buffer solution ; BR ; bicarbonate ringer ; QP ; amounts of drug permeated across cornea ; QR ; amounts of drug retained in the cornea ; TL ; lag time
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：25 September 2016
• 年：2016
• 卷：511
• 期：2
• 页码：719-727
• 全文大小：1866 K

文摘

Pranoprofen (PF) is a NSAID considered as a safe anti-inflammatory treatment for strabismus and/or cataract surgery. The drug has been formulated in poly (lactic/glycolic) acid (PLGA) nanoparticles (PF-F1NPs with cPF 1.5 mg/mL, PF-F2NPs with cPF 1 mg/mL) produced by solvent displacement technique and tested the in vitro cytotoxicity, ex vivo corneal permeation, in vivo ocular tolerance and in vivo anti-inflammatory efficacy of PF-F1NPs, PF-F2NPs, in comparison to eye drops conventional dosage form (Oftalar^®, PF 1 mg/mL) and free drug solution (PF dissolved in PBS, 1.5 mg/mL). The mean particle size of both formulations was around 350 nm, with polydispersity index below 0.1, and a net negative charge of −7.41 mV and −8.5 mV for PF-F1NPs and PF-F2NPs, respectively. Y-79 human retinoblastoma cell line was used to evaluate the cytotoxicity of PF-F1NPs and PF-F2NPs, which were compared to blank NPs and free drug solution (PF dissolved in PBS, 1.5 mg/mL). Concentrations up to 75 μg/mL exhibited no toxicity to Y-79 cells, whereas at 150 μg/mL a decrease of about 80% on the cell viability was observed after exposing the cells to PF-F1NPs. When treating the Y-79 cells with concentrations of PF-F2NPs between 1 μg/mL to 100 μg/mL, the cell viability was similar to control values after 24 h and 48 h of exposure. An ex vivo corneal permeation study was carried out in New Zealand rabbits. A very similar profile has been observed for the permeation of PF through the cornea when administered as eye drops and as free drug solution, which was kept much lower in comparison to PF-NPs formulations. The permeated amount of PF from the PF-F1NPs was slightly smaller than from PF-F2NPs, attributed to the increase of viscosity of the formulations with the increase of cPVA concentration. New Zealand white rabbits were also used to evaluate the irritancy of PF-F1NPs and PF-F2NPs, which demonstrated to be well-tolerated to the eye (i.e.   the mean total score (MTS) was 0). PF-F2NPs exhibited the highest Q_P$Q_P$ (amounts of PF permeated in the cornea) and significantly reduced the ocular edema compared to the tested formulations. The Q_R$Q_R$ (amounts of PF retained in the cornea) of the PF-F1NPs was greater than that obtained for PF-F2NPs.