De Cicco Felicetta, Porta Amalia, Sansone Francesca, Aquino Rita P, Del Gaudio Pasquale
Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132-84084 Fisciano Salerno, Italy.
Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132-84084 Fisciano Salerno, Italy.
Int J Pharm. 2014 Oct 1;473(1-2):30-7. doi: 10.1016/j.ijpharm.2014.06.049. Epub 2014 Jun 27.
In the current study the feasibility of the novel nano spray drying technique for the production of stable nanoparticulate dry powder, able to gel when administered locally on a wound, is explored. Gentamicin sulphate (GS) was loaded into alginate/pectin nanoparticles as highly soluble (hygroscopic) model drug with wide range antibacterial agent for wound dressing. The influence of process variables, mainly spray mesh size and feed concentration, on particle size and morphology, powder wound fluid uptake ability and gelling rate, as well as hydrogel water vapour transmission at wound site were studied. Particles morphology was spherical with few exceptions as slightly corrugated particles when the larger nozzle was used. Production of spherical nanoparticles (d50 ∼ 350 nm) in good yield (82-92%) required 4 μm spray mesh whereas 7 μm mesh produced larger wrinkled particles. Nano spray-dried particles showed high encapsulation efficiency (∼ 80%), good flowability, high fluid uptake, fast gel formation (15 min) and proper adhesiveness to fill the wound site and to remove easily the formulation after use. Moreover, moisture transmission of the in situ formed hydrogel was between 95 and 90 g/m(2)/h, an optimum range to avoid wound dehydration or occlusion phenomena. Release of the encapsulated GS, monitored as permeation rate using Franz cells in simulated wound fluid (SWF) was related to particle size and gelling rate. Sustained permeation profiles were obtained achieving total permeation of the drug between 3 and 6 days. However, all nano spray-dried formulations presented a burst effect, suitable to prevent infection spreading at the beginning of the therapy. Antimicrobial tests against Staphylococcus aureus and Pseudomonas aeruginosa showed stronger and prolonged antimicrobial effect of the nanoparticles compared to pure GS both shortly after administration and over time (till 12 days).
在当前研究中，探索了一种新型纳米喷雾干燥技术用于生产稳定的纳米颗粒干粉的可行性，该干粉在局部应用于伤口时能够形成凝胶。硫酸庆大霉素（GS）被载入藻酸盐/果胶纳米颗粒中，作为具有广泛抗菌作用的高溶性（吸湿性）模型药物用于伤口敷料。研究了工艺变量，主要是喷雾筛网尺寸和进料浓度，对颗粒大小和形态、粉末伤口液体吸收能力和胶凝速率，以及伤口部位水凝胶水蒸气透过率的影响。颗粒形态为球形，但使用较大喷嘴时，少数颗粒略显波纹。以良好的产率（82 - 92%）生产球形纳米颗粒（d50 ∼ 350 nm）需要4μm的喷雾筛网，而7μm的筛网会产生更大的有皱纹的颗粒。纳米喷雾干燥颗粒显示出高包封率（∼ 80%）、良好的流动性、高液体吸收性、快速凝胶形成（15分钟）以及适当的粘附性，以填充伤口部位并在使用后易于去除制剂。此外，原位形成的水凝胶的水分透过率在95至90 g/m²/h之间，这是避免伤口脱水或堵塞现象的最佳范围。在模拟伤口液（SWF）中使用Franz细胞监测包封的GS的释放，其渗透速率与颗粒大小和胶凝速率有关。获得了持续的渗透曲线，药物在3至6天内实现了完全渗透。然而，所有纳米喷雾干燥制剂都呈现出突释效应，适合在治疗开始时防止感染扩散。对金黄色葡萄球菌和铜绿假单胞菌的抗菌测试表明，与纯GS相比，纳米颗粒在给药后不久及一段时间内（直至12天）均表现出更强且持续时间更长的抗菌效果。
