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目的研究以胶体为核心的柔性纳米脂质体(flexible nano-liposomes,FNLs)包载蛋白类药物在肺部靶向递药的有效性和安全性。方法应用注入法结合W/W乳化法制备FNLs,并通过制剂学方法检测FNLs的理化性质。通过肺部滴注insulin-FNLs,检测相应血糖值;将异硫氰酸荧光素经肺部滴注给药,评估FNLs经肺转运进入体循环后药物在肺泡的沉积情况;通过对肺组织进行苏木素-伊红染色,初步评价FNLs经肺部给药的安全性。结果 FNLs形态圆整,表面光滑,粒径为(153±0.94)nm,Zeta电位为-(20.9±0.21)m V;FNLs能增强降血糖效果,提高相对生物利用度,最低血糖值百分比可以达到(18.25±4.19)%。FNLs能延长药物在肺内的滞留时间,在肺部具有较好的耐受性。结论 FNLs作为肺部靶向递药载体,经肺部给药可以克服蛋白类药物肺内吸收屏障,增加生物利用度,为新型肺内给药系统的研发奠定基础。
Objective To study the efficacy and safety of colloidal flexible nano-liposomes (FNLs) encapsulated drug delivery in the lungs. Methods FNLs were prepared by injection method and W / W emulsification method. The physicochemical properties of FNLs were determined by the method of pharmaceutics. Through the lung infusion of insulin-FNLs, the corresponding blood glucose levels; Fluorescein isothiocyanate drip lung administration, assessment of FNLs by lung transport into the systemic circulation of drugs in the alveolar deposition; by lung tissue hematoxylin - Eosin staining, preliminary assessment of the safety of FNLs delivered via the lungs. Results FNLs showed a round and smooth surface with a diameter of (153 ± 0.94) nm and a Zeta potential of - (20.9 ± 0.21) mV. FNLs could enhance hypoglycemic effect and increase relative bioavailability with the lowest percentage of blood glucose reaching (18.25 ± 4.19)%. FNLs can prolong the residence time of drugs in the lungs and have better tolerance in the lungs. CONCLUSION: FNLs, as a lung-targeted drug delivery carrier, can overcome the intrapulmonary absorption barrier of protein drugs and increase the bioavailability via pulmonary delivery, laying a foundation for the development of a new intrapulmonary drug delivery system.