Parra Alexander, Clares Beatriz, Rosselló Ana, Garduño-Ramírez María L, Abrego Guadalupe, García María L, Calpena Ana C
Department of Pharmacy and Pharmaceutical Technology, Biopharmaceutics and Pharmacokinetics Unit, Faculty of Pharmacy, University of Barcelona, Joan XXIII Avenue, 08028 Barcelona, Spain; Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Avenue, 08028 Barcelona, Spain.
Department of Pharmacy and Pharmaceutical Technology, University of Granada, Campus de la Cartuja Street, 18071 Granada, Spain.
Int J Pharm. 2016 Mar 30;501(1-2):10-7. doi: 10.1016/j.ijpharm.2016.01.056. Epub 2016 Jan 27.
The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-β-cyclodextrin (HPβCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans-epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (-23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation.
本研究的目的是开发用于卡洛芬（CP）经皮递送的聚（d，l-丙交酯-共-乙交酯）酸（PLGA）纳米颗粒（NPs）。然后使用羟丙基-β-环糊精（HPβCD）作为冷冻保护剂将所开发的纳米载体冻干。使用Franz扩散池，利用三种不同类型的皮肤膜（人皮肤、猪皮肤和牛皮肤）评估体外渗透曲线。此外，还测试了皮肤的生物力学特性（经表皮水分流失和皮肤水合作用）。最后，还测定了体内皮肤刺激性和抗炎功效。结果表明，所制备的纳米颗粒尺寸为187.32 nm，分布均匀，表面带负电荷（-23.39 mV），CP包封效率高（75.38%）。渗透研究表明，人皮肤和猪皮肤之间的扩散值相似，牛皮肤的扩散值更高。在兔子身上未观察到皮肤刺激迹象。在TPA诱导的小鼠耳水肿模型中，与参比药物相比，局部应用纳米颗粒显著降低了体内炎症。因此，得出结论，含CP的纳米颗粒可能是局部炎症皮肤治疗的有用工具。
