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用于鼻腔疫苗递送的表面改性聚乳酸-羟基乙酸共聚物纳米颗粒的研制与表征:粘膜粘附性包衣对抗原摄取和免疫佐剂活性的影响

Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity.

作者信息

Pawar Dilip, Mangal Sharad, Goswami Roshan, Jaganathan K S

机构信息

Department of Pharmaceutical Sciences, Jawaharlal Nehru Technical University, Hyderabad, India; Research and Development, Shantha Biotechnics Limited (A Sanofi Company), Hyderabad, India.

出版信息

Eur J Pharm Biopharm. 2013 Nov;85(3 Pt A):550-9. doi: 10.1016/j.ejpb.2013.06.017. Epub 2013 Jul 4.

Abstract

In this study, the efficacy of mucoadhesive polymers, i.e., chitosan and glycol chitosan as a mucoadhesive coating material in nasal vaccine delivery was investigated. The Hepatitis B surface Antigen (HBsAg) encapsulated PLGA, chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA) nanoparticles (NPs) were prepared. The formulations were characterized for particle size, shape, surface charge, and entrapment efficiency. The mucoadhesive ability of coated and non-coated NPs was determined using in vitro mucoadhesion and nasal clearance test. In addition, the systemic uptake and bio-distribution were also evaluated to understand the fate of NPs following nasal delivery. The immuno-adjuvant ability of various formulations was compared by measuring specific antibody titer in serum and secretory. The results indicated that PLGA NPs exhibit negative surface charge, whereas C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs demonstrated lower clearance and better local and systemic uptake compared to chitosan coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs could induce significantly higher systemic and mucosal immune response compared to PLGA and C-PLGA NPs. In conclusion, GC-PLGA NPs could be a promising carrier adjuvant for the nasal vaccine delivery for inducing a potent immune response at mucosal surface(s) and systemic circulation.

摘要

在本研究中,对作为鼻用疫苗递送中粘膜粘附包衣材料的粘膜粘附聚合物壳聚糖和乙二醇壳聚糖的功效进行了研究。制备了包封乙型肝炎表面抗原(HBsAg)的聚乳酸-羟基乙酸共聚物(PLGA)、壳聚糖包衣的PLGA(C-PLGA)和乙二醇壳聚糖包衣的PLGA(GC-PLGA)纳米颗粒(NPs)。对这些制剂的粒径、形状、表面电荷和包封率进行了表征。使用体外粘膜粘附和鼻腔清除试验测定了包衣和未包衣NPs的粘膜粘附能力。此外,还评估了全身摄取和生物分布,以了解鼻腔给药后NPs的命运。通过测量血清和分泌物中的特异性抗体滴度,比较了各种制剂的免疫佐剂能力。结果表明,PLGA NPs表现出负表面电荷,而C-PLGA和GC-PLGA NPs表现出正表面电荷。与壳聚糖包衣和未包衣的PLGA NPs相比,GC-PLGA NPs显示出更低的清除率以及更好的局部和全身摄取。体内免疫原性研究表明,与PLGA和C-PLGA NPs相比,GC-PLGA NPs可诱导显著更高的全身和粘膜免疫反应。总之,GC-PLGA NPs可能是一种有前景的鼻用疫苗递送载体佐剂,可在粘膜表面和全身循环中诱导有效的免疫反应。

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