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首个以α-生育酚为佐剂的口服疫苗的基于生理的药代动力学(PBPK)模型。

The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant.

作者信息

Saldanha Leonor, Vale Nuno

机构信息

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.

CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.

出版信息

Pharmaceutics. 2023 Sep 13;15(9):2313. doi: 10.3390/pharmaceutics15092313.

Abstract

Oral vaccines represent many advantages compared to standard vaccines. They hold a simple method of administration and manufacturing process. In addition to these, the way they can induce immune responses makes these a promising technology for the pharmaceutical industry and represents a new hope to society. Physiologically based pharmacokinetics (PBPK) has been used in support of drug development to predict the pharmacokinetics of the compound, considering the patient's physiology. Despite PBPK studies now being widely used, there are very few models in the literature that support vaccine development. Therefore, the goal of this article was to determine how PBPK could support vaccine development. The first PBPK model for an oral vaccine using alpha-tocopherol as a vaccine adjuvant was built. LogP is the parameter that influences the delivery of alpha-tocopherol into the tissues more. Having a high LogP means it accumulates in adipose tissue and is slowly metabolized. The ideal formulation to include alpha-tocopherol in an oral vaccine would incorporate nanoparticles in a capsule, and the dosage of the compound would be 150 mg in a volume of 200 mL. This article aims to determine if alpha-tocopherol, as a well-known adjuvant for intramuscular injection vaccines, could be used as an adjuvant to oral vaccines. This model was built considering the conditions and requirements needed for designing an oral vaccine. This implies making sure the antigen and adjuvants reach the main target by overcoming the challenges of the gastrointestinal tract. The main parameters that would need to be included in a formulation using alpha-tocopherol as an adjuvant were determined.

摘要

与标准疫苗相比,口服疫苗具有许多优势。它们具有简单的给药方法和生产工艺。除此之外,它们诱导免疫反应的方式使它们成为制药行业一项很有前景的技术,并为社会带来了新的希望。基于生理的药代动力学(PBPK)已被用于支持药物开发,以预测化合物的药代动力学,同时考虑患者的生理状况。尽管PBPK研究现在被广泛使用,但文献中支持疫苗开发的模型却非常少。因此,本文的目的是确定PBPK如何支持疫苗开发。构建了第一个以α-生育酚作为疫苗佐剂的口服疫苗PBPK模型。LogP是对α-生育酚进入组织的递送影响更大的参数。具有高LogP意味着它会在脂肪组织中积累并缓慢代谢。在口服疫苗中包含α-生育酚的理想制剂是在胶囊中加入纳米颗粒,化合物的剂量为200 mL中含150 mg。本文旨在确定作为肌肉注射疫苗的知名佐剂的α-生育酚是否可用作口服疫苗的佐剂。该模型是根据设计口服疫苗所需的条件和要求构建的。这意味着要通过克服胃肠道的挑战来确保抗原和佐剂到达主要靶点。确定了以α-生育酚作为佐剂的制剂中需要包含的主要参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2330/10535515/0f12b855efcd/pharmaceutics-15-02313-g001.jpg

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