Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of Louisiana at Monroe, 700 University Ave., Monroe, LA 71209, United States.
Department of Chemistry, Institute for Micromanufacturing, Louisiana Tech University, 911 Hergot Ave., Ruston, LA 71272, United States.
Int J Pharm. 2014 May 15;466(1-2):96-108. doi: 10.1016/j.ijpharm.2014.02.006. Epub 2014 Feb 22.
The present study tests the hypothesis that layer-by-layer (LbL) nanoassembly of thin polyelectrolyte films on insulin particles provides sustained release of the drug after pulmonary delivery. LbL insulin microparticles were formulated using cationic and anionic polyelectrolytes. The microparticles were characterized for particle size, particle morphology, zeta potential and in vitro release. The pharmacokinetics and pharmacodynamics of drug were assessed by measuring serum insulin and glucose levels after intrapulmonary administration in rats. Bronchoalveolar lavage (BAL) and evans blue (EB) extravasation studies were performed to investigate the cellular or biochemical changes in the lungs caused by formulation administration. The mass median aerodynamic diameter (MMAD) of the insulin microparticles was 2.7 μm. Confocal image of the formulation particles confirmed the polyelectrolyte deposition around the insulin particles. Zeta potential measurements showed that there was charge reversal after each layering. Pulmonary administered LbL insulin formulation resulted in sustained serum insulin levels and concomitant decrease in serum glucose levels. The BAL and EB extravasation studies showed that the LbL insulin formulation did not elicit significant increase in marker enzymes activities compared to control group. These results demonstrate that the sustained release of insulin could be achieved using LbL nanoassembly around the insulin particles.
通过逐层（LbL）组装将薄的聚电解质膜覆盖在胰岛素颗粒上，可以在肺部给药后提供药物的持续释放。使用阳离子和阴离子聚电解质来制备 LbL 胰岛素微球。对微球的粒径、颗粒形态、ζ电位和体外释放进行了表征。通过测量大鼠肺内给药后血清胰岛素和血糖水平，评估了药物的药代动力学和药效学。通过支气管肺泡灌洗（BAL）和伊文思蓝（EB）渗出研究，研究了制剂给药引起的肺部细胞或生化变化。胰岛素微球的质量中值空气动力学直径（MMAD）为 2.7μm。制剂颗粒的共焦图像证实了聚电解质在胰岛素颗粒周围的沉积。ζ电位测量表明，每次成层后都会发生电荷反转。肺部给予 LbL 胰岛素制剂可使血清胰岛素水平持续升高，并伴随血清葡萄糖水平降低。BAL 和 EB 渗出研究表明，与对照组相比，LbL 胰岛素制剂不会引起标记酶活性的显著增加。这些结果表明，通过在胰岛素颗粒周围进行 LbL 纳米组装可以实现胰岛素的持续释放。
