Subramanian Sneha, Khan Iftikhar, Korale Oshadie, Alhnan Mohamed Albed, Ahmed Waqar, Najlah Mohammad, Taylor Kevin M G, Elhissi Abdelbary
Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom; School of Medicine, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
Int J Pharm. 2016 Apr 11;502(1-2):18-27. doi: 10.1016/j.ijpharm.2016.01.070. Epub 2016 Feb 4.
Membrane extrusion was investigated for predicting the stability of soya phosphatidylcholine liposomes and surfactosomes (Tween 80-enriched liposomes) to nebulization. Formulations were prepared with or without cholesterol, and salbutamol sulfate (SBS) or beclometasone dipropionate (BDP) were incorporated as model hydrophilic or hydrophobic drugs respectively. Formulations were extruded through 5, 2, 1 and 0.4 μm polycarbonate membrane filters to study the influence of membrane pore size on drug retention by the vesicles. Surfactosomes were found to be very leaky to SBS, such that even without extrusion greater than 50% of the originally entrapped drug was lost; these losses were minimized by the inclusion of cholesterol. The smaller the membrane pore size, the greater the leakage of SBS; hence only around 10% were retained in cholesterol-free surfactosomes extruded through 0.4 μm filters. To study the influence of vesicle size on SBS retained entrapment, an excessive extrusion protocol was proposed (51 extrusion cycles through 1 μm filters) to compare the stability of freshly prepared vesicles (i.e. unextruded; median size approx. 4.5-6.5 μm) with those previously extruded through 1 μm pores. Cholesterol was essential for minimizing losses from liposomes, whilst for surfactosomes size reduction prior to extrusion was the only way to minimize SBS losses which reached up to 93.40% of the originally entrapped drug when no cholesterol was included. When extrusion was applied to BDP-loaded vesicles, greater proportions of the drug were retained in the vesicles compared to SBS. Even with extrusion through 0.4 μm, BDP retention was around 50-60% with little effect of formulation. Excessive extrusion showed BDP retention using small liposomes (1 μm) to be as high as 71-87%, compared to 50-66% for freshly prepared vesicles. The findings, based on extrusion, were compared to studies of vesicle stability to nebulization, published by a range of investigators. It was concluded that extrusion is a valid method for predicting the stability of liposomes to nebulization.
研究了膜挤压法预测大豆磷脂酰胆碱脂质体和表面活性剂体（富含吐温80的脂质体）雾化稳定性的情况。制备了含或不含胆固醇的制剂，并分别加入硫酸沙丁胺醇（SBS）或丙酸倍氯米松（BDP）作为亲水性或疏水性模型药物。将制剂通过5、2、1和0.4μm的聚碳酸酯膜过滤器挤出，以研究膜孔径对囊泡药物保留率的影响。发现表面活性剂体对SBS的渗漏非常严重，以至于即使不进行挤压，最初包封的药物也会损失超过50%；加入胆固醇可将这些损失降至最低。膜孔径越小，SBS的渗漏越大；因此，通过0.4μm过滤器挤出的无胆固醇表面活性剂体中，只有约10%的药物被保留。为了研究囊泡大小对SBS保留包封率的影响，提出了一种过度挤压方案（通过1μm过滤器进行51次挤压循环），以比较新制备的囊泡（即未挤压；中位大小约为4.5 - 6.5μm）与先前通过1μm孔径挤出的囊泡的稳定性。胆固醇对于将脂质体的损失降至最低至关重要，而对于表面活性剂体，挤压前减小尺寸是将SBS损失降至最低的唯一方法，当不加入胆固醇时，SBS损失可达最初包封药物的93.40%。当对负载BDP的囊泡进行挤压时，与SBS相比，更大比例的药物保留在囊泡中。即使通过0.4μm进行挤压，BDP的保留率仍约为50 - 60%，制剂的影响很小。过度挤压显示，使用小脂质体（1μm）时BDP的保留率高达71 - 87%，而新制备的囊泡为50 - 66%。将基于挤压的研究结果与一系列研究人员发表的囊泡雾化稳定性研究进行了比较。得出的结论是，挤压是预测脂质体雾化稳定性的有效方法。
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